Bioactive Glasses for Soft Tissue Engineering Applications - Miguez-Pacheco, Valentina; Gorustovich, Alejandro A.; Boccaccini, Aldo R.; Roether, Judith (Bioactive Glasses: Fundamentals, Technology and Applications, 2017)
In the last few years the usage of bioactive glasses as scaffolds for soft tissue engineering has been investigated more thoroughly. The reason for the boost in interest is the attractive properties bioactive glasses offer, including bioactivity as well as antibacterial, angiogenic and hemostatic properties. So far, most research efforts have focused on applications for repairing skin and nerve tissue although there have been interesting developments in other fields including lung and intestine, which could potentially benefit a large group of patients. Three review articles on this topic have been published, so this chapter will mainly focus on the latest relevant findings. A great number of patents have been registered for the use of bioactive glass for hard tissue engineering. Recently, however, patents have been filed detailing the use of bioactive glass for soft tissue engineering applications which open the way to marketing bioactive glasses for soft tissue repair. The angiogenic effect of bioactive glasses and their dissolution products is of great interest for tissue engineering applications in general and in particular for soft tissue regeneration and repair. The third part of this chapter will detail the latest research on these angiogenic properties of bioactive glasses.
CRIS-Team Scopus Importer:2022-08-05

Bioactive glasses incorporating less-common ions to improve biological and physical properties - Pantulap, Usanee; Arango Ospina, Marcela; Boccaccini, Aldo R. (Journal of Materials Science: Materials in Medicine, 2022)
Bioactive glasses (BGs) have been a focus of research for over five decades for several biomedical applications. Although their use in bone substitution and bone tissue regeneration has gained important attention, recent developments have also seen the expansion of BG applications to the field of soft tissue engineering. Hard and soft tissue repair therapies can benefit from the biological activity of metallic ions released from BGs. These metallic ions are incorporated in the BG network not only for their biological therapeutic effects but also in many cases for influencing the structure and processability of the glass and to impart extra functional properties. The "classical" elements in silicate BG compositions are silicon (Si), phosphorous (P), calcium (Ca), sodium (Na), and potassium (K). In addition, other well-recognized biologically active ions have been incorporated in BGs to provide osteogenic, angiogenic, anti-inflammatory, and antibacterial effects such as zinc (Zn), magnesium (Mg), silver (Ag), strontium (Sr), gallium (Ga), fluorine (F), iron (Fe), cobalt (Co), boron (B), lithium (Li), titanium (Ti), and copper (Cu). More recently, rare earth and other elements considered less common or, some of them, even "exotic" for biomedical applications, have found room as doping elements in BGs to enhance their biological and physical properties. For example, barium (Ba), bismuth (Bi), chlorine (Cl), chromium (Cr), dysprosium (Dy), europium (Eu), gadolinium (Gd), ytterbium (Yb), thulium (Tm), germanium (Ge), gold (Au), holmium (Ho), iodine (I), lanthanum (La), manganese (Mn), molybdenum (Mo), nickel (Ni), niobium (Nb), nitrogen (N), palladium (Pd), rubidium (Rb), samarium (Sm), selenium (Se), tantalum (Ta), tellurium (Te), terbium (Tb), erbium (Er), tin (Sn), tungsten (W), vanadium (V), yttrium (Y) as well as zirconium (Zr) have been included in BGs. These ions have been found to be particularly interesting for enhancing the biological performance of doped BGs in novel compositions for tissue repair (both hard and soft tissue) and for providing, in some cases, extra functionalities to the BG, for example fluorescence, luminescence, radiation shielding, anti-inflammatory, and antibacterial properties. This review summarizes the influence of incorporating such less-common elements in BGs with focus on tissue engineering applications, usually exploiting the bioactivity of the BG in combination with other functional properties imparted by the presence of the added elements.
CRIS-Team WoS Importer:2021-12-31

Bioactive glasses in soft tissue repair - Miguez-Pacheco, Valentina; Greenspan, David; Hench, Larry L.; Boccaccini, Aldo R. (American Ceramic Society Bulletin, 2015)

Bioactive glasses meet phytotherapeutics: The potential of natural herbal medicines to extend the functionality of bioactive glasses - Schuhladen, Katharina; Roether, Judith; Boccaccini, Aldo R. (Biomaterials, 2019)
Herbal medicine, the use of plants or plant extracts with known beneficial biological effects to treat and/or prevent diverse health disorders, has been known for thousands of years. After their replacement by synthetic drugs in the beginning of the 20th century, plant derived therapeutic agents have been recently attaining more attention again. Phytotherapeutics, which can be extracted from a wide range of different herbal plants, are believed to have a broad spectrum of therapeutic effects and less negative side effects than synthetic drugs. On the other hand, it is often difficult to prove the therapeutic effect of herbal drugs due to their chemical complexity. In the last decade, research has focused increasingly on the relatively new concept of the combination of herbal drugs with modern engineered biomaterials in order to achieve synergy of their therapeutic effects. Even if several studies based on this concept have been published, no systematic overview of the performed investigations and their results is available. In this context, this review focuses on the combination of phytotherapeutics with bioactive glasses (BGs), which are bioactive and biodegradable materials capable of releasing biologically active ions being suitable for several applications as bone substituting and replacing materials as well as in the regeneration of soft and hard tissue. The literature search was carried out using the WEB OF SCIENCE® and SCOPUS® databases using a combination of relevant keywords. Besides giving an overview of the research done in the last years and summarizing the results obtained in those studies, the possible synergistic effects of herbal drugs in combination with BGs are critically discussed, and potential health risks are overviewed. Of all plant-derived drugs investigated so far, the coumarin family appears to be the one that has been most widely combined with BGs showing beneficial outcomes. Overall, the analysis of the literature has revealed the great potential of this organic-inorganic multi-functional system approach as an advantageous alternative to conventional medicine in several applications, but also highlights the need for more systematic in vivo studies to evaluate the effective time and dose dependent combined effects of BGs and phytotherapeutic agents.
CRIS-Team Scopus Importer:2019-07-02
Keywords: Bioactive glass; Composite; Drug delivery; Phytotherapeutics; Synergistic effect

Bioactive glasses: Special applications outside the skeletal system - Baino, Francesco; Novajra, Giorgia; Miguez Pacheco, Valentina; Boccaccini, Aldo R.; Vitale-Brovarone, Chiara (Journal of Non-Crystalline Solids, 2016)
Bioactive glasses were invented 45 years ago and have been in clinical use since the 1980s in otology, orthopaedics and dentistry. Initially born as bioactive materials to fill bone defects, bioactive glasses expanded their biomedical suitability towards a broad spectrum of tissue engineering and therapeutic applications, and research evolution seems to witness that their potential is far from being fully exploited. Classical applications of bioactive glasses involve bone filling materials and dental implants; however, the fascinating question to be answered in the next few years is: how can bioactive glasses be useful in soft tissue regeneration and to treat diseases, such as tumours, that may affect internal organs? This review paper focuses on research that demonstrates the suitability of bioactive glasses in contact with tissues outside the skeletal system, including muscle and nerve tissue regeneration, treatment of diseases affecting sense organs (eye and ear), embolization of neoplastic tissues, cancer radiotherapy via injectable microspheres, and wound dressing. A prospect for future research is also provided, highlighting the potential associated to targeted therapy via local ion release, angiogenesis stimulation and in situ drug release, as well as the promise of biofabrication for the development of bioactive glass-containing composite constructs for organ regeneration.
Keywords: Angiogenesis; Antibacterial properties; Bioglass; Cancer treatment; Composites

Bioactive glasses: Traditional and prospective applications in healthcare - Li, Wei; Boccaccini, Aldo R. (Hot Topics in Biomaterials, 2014)
Bioactive glasses attract great interest for a variety of healthcare applications due to their versatile properties.
CRIS-Team Scopus Importer:2022-08-05

Bioactive Glass Fiber-Reinforced PGS Matrix Composites for Cartilage Regeneration - Trevelin Souza, Marina; Tansaz, Samira; Dutra Zanotto, Edgar; Boccaccini, Aldo R. (Materials, 2017)
Poly(glycerol sebacate) (PGS) is an elastomeric polymer which is attracting increasing interest for biomedical applications, including cartilage regeneration. However, its limited mechanical properties and possible negative effects of its degradation byproducts restrict PGS for in vivo application. In this study, a novel PGS–bioactive glass fiber (F18)-reinforced composite was developed and characterized. PGS-based reinforced scaffolds were fabricated via salt leaching and characterized regarding their mechanical properties, degradation, and bioactivity in contact with simulated body fluid. Results indicated that the incorporation of silicate-based bioactive glass fibers could double the composite tensile strength, tailor the polymer degradability, and improve the scaffold bioactivity.
Keywords: poly(glycerol sebacate); bioactive glass; fibers; composite; cartilage; tissue engineering

Bioactive Glass Flakes as Innovative Fillers in Chitosan Membranes for Guided Bone Regeneration - Zhang, Huijun; Wu, Jingjing; Wan, Ying; Romeis, Stefan; Esper, Julian Duane; Peukert, Wolfgang; Zheng, Kai; Boccaccini, Aldo R. (Advanced Engineering Materials, 2021)
Herein, novel bioactive glass flakes (BGFs) (45S5 composition), obtained by compression in the liquid phase in a stirred media mill, are combined with chitosan (CS) to develop composite membranes using solvent casting for guided bone regeneration (GBR). The incorporation of BGFs endows CS membranes with superior bioactivity as evidenced by rapid hydroxyapatite formation after 3 days of immersion in simulated body fluid (SBF). Moreover, the addition of BGFs reduces the swelling ratio of CS membranes, beneficial for GBR applications. The swelling behavior can also be modulated by tuning the added amount of BGFs. In vitro cell studies indicate the noncytotoxicity of composite membranes toward osteoblast cell line MC3T3-E1, although the presence of BGFs slightly reduces the cell viability compared to pure CS membranes. The incorporation of BGFs also improves the osteogenic differentiation of MC3T3-E1 cells as indicated by the enhanced alkaline phosphatase activity. The results show the feasibility of BGFs as anisotropic bioactive fillers in polymeric matrices. In conclusion, the developed CS-BGF composite membranes show promising potential as a novel material for GBR.
CRIS-Team Scopus Importer:2021-10-08
Keywords: bioactive fillers; bioactive glass flakes; chitosan; composites; guided bone regeneration

Bioactive glass foams for tissue engineering applications - Hoppe, Alexander; Boccaccini, Aldo R. (Elsevier Ltd., 2014)
Bioactive glasses have been widely used in the field of bone tissue engineering due to their appropriate biological and mechanical properties. In this chapter we will review recent developments in fabricating bioactive-glass-derived 3D foams (scaffolds), discussing also their structural and biological properties. The most common fabrication routes will be presented and discussed. Further key findings from in vitro and in vivo studies on bioactive glass scaffolds will be presented in order to support the concept of the use of bioactive glass in (bone) tissue engineering applications. In addition to the 'standard' silicate-based bioactive glass compositions, representative findings on novel glass compositions for biomedical use, e.g. containing therapeutic metal ions, will be highlighted. © 2014 Woodhead Publishing Limited. All rights reserved.
Keywords: Bioactive glass; Biomedical foams; Osteogenesis; Scaffolds; Tissue engineering

Bioactive Glass Inhibits Tumor Development from Giant Cell Tumor of Bone-Derived Neoplastic Stromal Cells in a Chicken Chorioallantoic Membrane Assay - Fellenberg, Joerg; Losch, Sarina; Marinescu, Max R.; Frey, Birgit; Lehner, Burkhard; Arango-Ospina, Marcela; Hadzhieva, Zoya; Boccaccini, Aldo R.; Westhauser, Fabian (Cancers, 2023)
Tumor recurrence is a major problem during the treatment of giant cell tumors of bone (GCTB). We recently identified tumor cell-specific cytotoxic effects of bioactive glasses (BGs) toward neoplastic stromal cells derived from GCTB tissue (GCTSCs) in vitro. Since these data indicated a promising role of BGs in the adjuvant treatment of GCTBs, we aimed to investigate the transferability of the in vitro data into the more complex in vivo situation in the current study. We first analyzed the cytotoxicity of three different BGs in vitro by WST-1 assay after co-cultivation with primary GCTSC cell lines. The effects of BGs on tumor engraftment and growth were analyzed by chicken chorioallantoic membrane (CAM) assays and subsequent quantification of tumor take rates and tumor volumes. In vitro, all tested BGs displayed a cytotoxic effect on GCTSCs that was dependent on BG composition, concentration, and particle size. Comparable effects could be observed within the in vivo environment resulting in reduced tumor take rates and tumor volumes in BG-treated samples. These data indicate a possible clinical application of BGs in the context of GCTB therapy, mediating a reduction of recurrence rates with the simultaneous promotion of bone regeneration.
CRIS-Team Scopus Importer:2023-04-14
Keywords: bioactive glass; chorioallantoic membrane assay; giant cell tumor of bone

Bioactive glass selectively promotes cytotoxicity towards giant cell tumor of bone derived neoplastic stromal cells and induces MAPK signalling dependent autophagy - Fellenberg, Joerg; Losch, Sarina; Lehner, Burkhard; Arango Ospina, Marcela; Boccaccini, Aldo R.; Westhauser, Fabian (Bioactive Materials, 2022)
Giant cell tumors of bone (GCTB) are associated with massive bone destructions and high recurrence rates. In a previous study, we observed cytotoxic effects of three different compositions of bioactive glasses (BGs) towards GCTSC but not bone marrow derived stromal cells (BMSC) indicating that BGs represent promising candidates for the development of new therapeutic approaches. In the current study we aimed to investigate the molecular mechanisms that are involved in BG induced cytotoxicity. We observed, that BG treatment was not associated with any signs of apoptosis, but rather led to a strong induction of mitogen activated protein kinases (MAPK) and, as a consequence, upregulation of several transcription factors specifically in GCTSC. Genome wide gene expression profiling further revealed a set of fifteen genes that were exclusively induced in GCTSC or induced significantly stronger in GCTSC compared to BMSC. BG treatment further induced autophagy that was significantly more pronounced in GCTSC compared to BMSC and could be inhibited by MAPK inhibitors. Together with the known osteogenic properties of BGs our findings support the suitability of BGs as therapeutic agents for the treatment of GCTB. However, these data have to be verified under in vivo conditions.
CRIS-Team Scopus Importer:2022-03-11
Keywords: Autophagy; Bioactive glass; Cytotoxicity; Giant cell tumor of bone; Mesenchymal stromal cells; Mitogen-activated protein kinases

Bioactive glass (type 45S5) nanoparticles: in vitro reactivity on nanoscale and biocompatibility - Mackovic, Mirza; Hoppe, Alexander; Detsch, Rainer; Mohn, Dirk; Stark, W. J.; Spiecker, Erdmann; Boccaccini, Aldo R. (Journal of Nanoparticle Research, 2012)
Bioactive glasses represent important biomaterials being investigated for the repair and reconstruction of diseased bone tissues, as they exhibit outstanding bonding properties to human bone. In this study, bioactive glass (type 45S5) nanoparticles (nBG) with a mean particle size in the range of 20–60 nm, synthesised by flame spray synthesis, are investigated in relation to in vitro bioreactivity in simulated body fluid (SBF) and response to osteoblast cells. The structure and kinetics of hydroxyapatite formation in SBF were investigated using transmission electron microscopy (TEM), X-ray diffraction (XRD) and Fourier-transform infrared spectroscopy (FT-IR) revealing a very rapid transformation (after 1 day) of nBG to nanocrystalline bone-like carbonated HAp. Additionally, calcite is formed after 1 day of SBF immersion because of the high surface reactivity of the nBG particles. In the initial state, nBG particles were found to exhibit chain-like porous agglomerates of amorphous nature which are transformed on immersion in SBF into compact agglomerates covered by hydroxyapatite with a reduced size of the primary nanoparticles. In vitro studies revealed high cytocompatibility of nBG with human osteoblast cells, indicated through high lactatedehydrogenase (LDH) and mitochondrial activity as well as alkaline phosphatase activity. Hence, this study contributes to the understanding of the structure and bioactivity of bioactive glass (type 45S5) nanoparticles, providing insights to the phenomena occurring at the nanoscale after immersion in SBF. The results are relevant in relation to the understanding of the nanoparticles’ bioreactivity required for applications in bone tissue engineering.
UnivIS-Import:2015-03-09:Pub.2013.tech.IW.LM.bioact
Keywords: Nanoparticles; Bioactive glass; TEM; Hydroxyapatite; Osteoblast

Bioactive glass variants for tissue engineering: From the macro- to the nanoscale - Schuhladen, Katharina; Boccaccini, Aldo R. (Elsevier, 2020)
Bioactive glass (BG), a typical example for a third-generation biomaterial, shows great success in the regeneration, repair, and replacement of damaged tissue, due its ability to release therapeutic ions and to form an apatite layer during dissolution in physiological fluids. Since the development of the first bioactive glass 50years ago, different glass compositions and fabrication methods have led to the development of a wide variety of bioactive glasses, some of them being highly relevant for tissue engineering applications, both hard and soft tissues. With ongoing development of advanced fabrication methods, a reduction in bioactive glass dimensions (e.g., particle size) from macroscopic to nanosize has been achieved. This chapter presents a summary of achievements of 50years of research on bioactive glasses for tissue engineering and drug delivery applications highlighting the three kinds of bioactive glasses linking applications in the field, namely, melt-derived, sol-gel-derived, and mesoporous BGs.
CRIS-Team Scopus Importer:2024-12-16
Keywords: Bioactive glasses; Drug delivery; Ion release; Scaffolds; Sol-gel; Tissue engineering

Bioactive Inks Development for Osteochondral Tissue Engineering: A Mini-Review - Bakhtiary, Negar; Liu, Chaozong; Ghorbani, Farnaz (Gels, 2021)
Nowadays, a prevalent joint disease affecting both cartilage and subchondral bone is osteoarthritis. Osteochondral tissue, a complex tissue unit, exhibited limited self-renewal potential. Furthermore, its gradient properties, including mechanical property, bio-compositions, and cellular behaviors, present a challenge in repairing and regenerating damaged osteochondral tissues. Here, tissue engineering and translational medicine development using bioprinting technology provided a promising strategy for osteochondral tissue repair. In this regard, personalized stratified scaffolds, which play an influential role in osteochondral regeneration, can provide potential treatment options in early-stage osteoarthritis to delay or avoid the use of joint replacements. Accordingly, bioactive scaffolds with possible integration with surrounding tissue and controlling inflammatory responses have promising future tissue engineering perspectives. This minireview focuses on introducing biologically active inks for bioprinting the hierarchical scaffolds, containing growth factors and bioactive materials for 3D printing of regenerative osteochondral substitutes.
CRIS-Team WoS Importer:2022-02-04

Bioactive layers based on black glasses on titanium substrates - Gaweda, Magdalena; Jelen, Piotr; Dlugon, Elzbieta; Wajda, Aleksandra; Lesniak, Magdalena; Simka, Wojciech; Sowa, Maciej; Detsch, Rainer; Boccaccini, Aldo R.; Sitarz, Maciej (Journal of the American Ceramic Society, 2017)
Keywords: bioceramics; biocompatibility; coating; silicon oxycarbide; sol-gel

Bioactive Nanocomposites Containing Silicate Phases for Bone Replacement and Regeneration - Erol, Melek M.; Hum, Jasmin; Boccaccini, Aldo R. (Wiley-VCH, 2012)
Engineered scaffolds made from synthetic or natural biomaterials are essential elements in bone tissue engineering approaches. Numerous biomaterials are being used to fabricate scaffolds, including glasses, ceramics, metals, polymers, and their composites. Many of these scaffold structures are similar to the hierarchical bone structure; however, several challenges in the design, fabrication, and characterization of scaffolds remain in order to fulfill all requirements for bone tissue engineering applications. Nanostructures represent a very important consideration when developing composite scaffolds that mimic the nanofeatures of bone consisting of inorganic-organic structures on the nanoscale. In this chapter, a complete overview of the technology, characterization, and application of nanoparticles and nanofibrous silicate materials, including bioactive glasses, silica, and clay, in the context of bone tissue scaffold development, is presented. Also, the physicochemical, mechanical, and biological advantages of incorporating nanoscale bioactive glasses, silica, and clay in nanocomposites are discussed with emphasis on recently developed nanocomposites based on nanoscale silicate inclusions and biopolymer matrices. © 2012 Wiley-VCH Verlag GmbH & Co. KGaA.
Keywords: Bioactive glasses; Bone tissue engineering; Nanoclays; Nanocomposites; Nanoparticles; Silica

Bioactive nanocomposites for dental application obtained by reactive suspension method - Boumezgane, Oussama; Bondioli, Frederica; Bortolini, Sergio; Natali, Alfredo; Boccaccini, Aldo R.; Boccardi, Elena; Messori, Massimo (Nanocomposites, 2016)

Bioactive Phosphate Glasses - Lapa, Agata (Friedrich-Alexander-Universität Erlangen-Nürnberg, 2018)

Bioactivity and dissolution behavior of boron-containing bioactive glasses under static and dynamic conditions in different media - Arango Ospina, Marcela; Hupa, Leena; Boccaccini, Aldo R. (Biomedical Glasses, 2019)
Keywords: silicate glasses; Bioactive glasses; boron; bioactivity; lactic acid; dynamic dissolution

Bioactivity and Mechanical Stability of 45S5 Bioactive Glass Scaffolds Based on Natural Marine Sponges - Boccardi, Elena; Philippart, Anahi; Melli, V.; Altomare, Lina; De Nardo, L.; Novajra, G.; Vitale-Brovarone, C.; Fey, Tobias; Boccaccini, Aldo R. (Annals of Biomedical Engineering, 2016)
Keywords: Bioactive glass scaffolds; Biocompatibility; Natural marine sponges; Osteoblasts; Simulated body fluid

Bioactivity, mechanical properties and drug delivery ability of bioactive glass-ceramic scaffolds coated with a natural-derived polymer - Araujo, Marco; Viveiros, Raquel; Philippart, Anahi; Miola, M.; Doumett, S.; Baldi, G.; Perez, J.; Boccaccini, Aldo R.; Aguiar-Ricardo, Ana; Verne, E. (Materials Science and Engineering C, 2017)
Keywords: Drug delivery; Ibuprofen; Mechanical properties; Melanin; Scaffolds; Supercritical CO2

Bioactivity of electro-thermally poled bioactive silicate glass - Boccaccini, Aldo R.; et al. (Acta Biomaterialia, 2009)
A 45S5 bioactive glass (nominal composition: 46.1 mol.% SiO2, 2.6 mol.% P2O5, 26.9 mol.% CaO, 24.4 mol.% Na2O) was electrothermally poled by applying voltages up to 750 V for 45 min at 200 °C, and the thermally stimulated depolarization currents (TSDCs) were recorded. Changes in chemical composition and electrical properties after poling were investigated by TSDC measurements, impedance spectroscopy and scanning electron microscopy with energy dispersive X-ray spectroscopy (SEM/EDX). The poling led to the formation of interfacial layers underneath the surface in contact with the electrodes. Under the positive electrode, the layer was characterized by Na+ ion depletion and by a negative charge density, and the layer was more resistive than the bulk. The influence of poling on the bioactivity was studied by immersion of samples in simulated body fluid (SBF) with subsequent cross-sectional SEM/EDX and X-ray diffraction analysis. It was found that poling leads to morphological changes in the silica-rich layer and to changes in the growth rate of amorphous calcium phosphate and bone-like apatite on the glass surface. The bone-like apatite layer under the positive electrode was slightly thicker than that under the negative electrode. © 2008 Acta Materialia Inc.
UnivIS-Import:2015-03-09:Pub.2009.tech.IW.LM.bioact
Keywords: Apatite; Bioactive glass; SBF; Surface charge; Thermal poling

Bioactivity of polyurethane-based scaffolds coated with Bioglass - Boccaccini, Aldo R.; et al. (Biomedical Materials, 2007)
Polyurethane (PUR) and polyurethane/poly(D, L-lactide) acid (PUR/PDLLA) based scaffolds coated with Bioglass® particles for application in bone tissue engineering were fabricated. The slurry-dipping method was used for coating preparation. The homogeneous structure of the Bioglass® coatings on the surface of the PUR and PUR/PDLLA foams indicated a good adhesion of the bioactive glass particles to polyurethane without any additional surface treatment. In vitro studies in simulated body fluid (SBF) were performed to study the influence of Bioglass® coating on biodegrability and bioactivity of PUR-based scaffolds. The surface of Bioglass®-coated samples was covered by a layer of carbonate-containing apatite after 7 days of immersion in SBF, while in uncoated polymer samples apatite crystals were not detected even after 21 days of immersion in SBF. The apatite layer was characterized by scanning electron microscopy (SEM), EDS analysis and attenuated total reflectance-Fourier transform infrared spectrometry (FTIR-ATR). Weight loss measurements showed that the in vitro degradation rate of the composite scaffolds in SBF was higher in comparison to uncoated polyurethane samples. PUR and PUR/PDLLA foams with Bioglass® coating have potential to be used as bioactive, biodegradable scaffolds in bone tissue engineering. © 2007 IOP Publishing Ltd.
UnivIS-Import:2015-03-09:Pub.2007.tech.IW.LM.bioact

Bioactivity of radiopaque 45S5 bioactive glass with progressive additions of Bi2O3: A dissolution study under static conditions - Clavijo-Mejía, G. A.; Michálek, M.; Youssef, L.; Kaňková, H.; Galusek, D.; Boccaccini, Aldo R. (Ceramics International, 2024)
The integration of bioactive glasses (BGs) into hard tissues in in-vivo models can be evaluated through X-ray radiographs. The image contrast plays an important role and should be enhanced to improve accurate minimal invasive diagnostics of the performance of BGs containing implants after surgery. The present work shows the effect of the progressive addition of Bi2O3 (up to 12.2 wt%) on the structure, thermal properties, radiopacity, and bioactivity of 45S5-like BG obtained by quenching of the melt prepared from oxide precursors. The BG chemical composition, phase composition, structure, chemical state, thermal properties, and radiopacity were respectively investigated by X-ray fluorescence (XRF), X-ray diffraction (XRD), Raman spectroscopy, X-ray photoelectron spectroscopy (XPS), differential scanning calorimetry (DSC), and radiopacity analysis according to the ISO13116:2014 norm. The bioactivity of the glasses was monitored by immersing them in a simulated body fluid (SBF) under static conditions. The apatite formation ability and ion concentration in SBF after 3, 7, 14, and 21 days were investigated by XRD, scanning electron microscopy (SEM), inductively coupled plasma optical emission spectroscopy (ICP-OES), and ICP mass spectrometry (ICP-MS). All samples were found to be X-ray amorphous. Simultaneous formation of [BiO3] and [BiO6] units is noted in the BG. The glass radiopacity increased up to 1.8 and 4.2 times compared to the reference glasses without Bi2O3. Bi2O3 additions in the glass slow down the formation of apatite-like structures as a result of the network forming role of [BiO3] and [BiO6] units in the BG. Nevertheless, the BGs with the 12.2 wt % Bi2O3 still shows the ability to form apatite deposits after 7 days of immersion in simulated body fluid (SBF).
CRIS-Team Scopus Importer:2024-05-10
Keywords: Bioactive glass 45S5; Bioactivity; Bismuth oxide; Radiopacity

Bioactıve Glass-Polymer Nanocomposites for Bone Tıssue Regeneration Applicatıons: A Revıew - Erol-Taygun, Melek; Ünalan, Irem; Idris, Maizlinda Izwana Binti; Mano, João F.; Boccaccini, Aldo R. (Advanced Engineering Materials, 2019)
Nanosized bioactive glass (NBG) particles are attractive materials for bone repair because of their ability to enhance bone formation and to chemically bond to the surrounding bone tissue. In recent years, composites of biopolymers and NBG particles have been developed for bone tissue engineering due to their increased bioactivity, biocompatibility, and biodegradability. In this paper, the authors review current knowledge regarding polymer/NBG composites, including nanoscale-related features and ion-release effects of bioactive glass (BG) with respect to osteogenic and angiogenic responses in vivo and in vitro; the authors also focus on the techniques used to fabricate these nanocomposites. Additionally, this review discusses recent developments in the use of nanocomposites for tissue engineering and represents a literature update, as well an expansion, of previously published articles on this topic.
CRIS-Team Scopus Importer:2019-07-16
Keywords: angiogenesis; bioactive glasses; bone tissue engineering; composites; ion release; nanoparticles; osteogenesis; scaffolds

Bioaktive Glas-Scaffolds beschichtet mit Zein, einem pflanzlichen Protein: Entwicklung und Eigenschaften - Hum, Jasmin; Potschka, Jonathan; Boccaccini, Aldo R. (Keramische Zeitschrift, 2017)
Keywords: Bioaktives Glas; Scaffolds; Zein

Bioaktive Glas-Scaffolds beschichtet mit Zein, einem pflanzlichen Protein: Entwicklung und Eigenschaften - Hum, Jasmin; Potschka, Jonathan; Boccaccini, Aldo R. (Keramische Zeitschrift, 2017)
The present study describes the coating of porous scaffolds (based on 45S5 bioactive glass and produced by the foam replica method) with zein, a storage protein derived from corn. As bioactive scaffolds show microcracks on the surface, the mechanical performance is very weak. By applying a polymer layer, these cracks can be filled and bridged, which leads to enhanced fracture strength and toughness. Therefore, bioactive glass-based scaffolds are immersed in a zein solution. After evaporation of the solvent, a thin polymer film of 10 μm remains on the surface. The microstructure and morphology were investigated by scanning electron microscopy (SEM). Furthermore, the influence of the coating on the bioactive behavior of the scaffolds was tested by immersion in simulated body fluid (SBF). The formation of hydroxyapatite was analyzed by SEM and Fourier Transform Infrared Spectrometry (FTIR). By applying a zein coating, the compressive strength was increased by factor 5.
CRIS-Team Scopus Importer:2022-08-05
Keywords: Bioaktives Glas; Scaffolds; Zein

Bioceramics for tissue engineering and drug delivery - Boccaccini, Aldo R. (Advances in Applied Ceramics, 2008)
UnivIS-Import:2015-03-09:Pub.2008.tech.IW.LM.biocer

Biocompatibility and bioactivity of PDLLA/TiO2 and PDLLA/TiO2/Bioglasss (R) nanocomposites - Wei, J.; Chen, Q. Z.; Stevens, M. M.; Roether, J. A.; Boccaccini, Aldo R. (Materials Science and Engineering C, 2008)
UnivIS-Import:2015-03-09:Pub.2008.tech.IW.LM.biocom

Biocompatibility and bone mineralization potential of 45S5 Bioglasso (R)-derived glass-ceramic scaffolds in chick embryos - Vargas, Gabriela E.; Vera Mesones, Rosa; Bretcanu, Oana; Porto Lopez, Jose M.; Boccaccini, Aldo R.; Gorustovich, Alejandro (Acta Biomaterialia, 2009)
UnivIS-Import:2015-03-09:Pub.2009.tech.IW.LM.biocom

Biocompatibility of submicron Bioglass® powders obtained by a top-down approach - Dörfler, Anja; Detsch, Rainer; Romeis, Stefan; Schmidt, Jochen; Eisermann, Claudia; Peukert, Wolfgang; Boccaccini, Aldo R. (Journal of Biomedical Materials Research Part B: Applied Biomaterials, 2014)
In this study in vitro bioactivity and biocompatibility of two submicron 45S5 Bioglass powders obtained by top-down processing have been evaluated and are compared to the as-received powder. Both submicron powders exhibited flake-like morphologies with lateral extensions of only a few microns; the flake thickness accounted for a few tens of nanometers. Enhanced in vitro bioactivity was found for the comminuted powders upon immersion in simulated body fluid. In vitro biocompatibility was evaluated by incubation of MG-63 osteoblast-like cells with various amounts (0-200 μg/mL) of the glass powders. Neither LDH-activity nor mitochondrial activity (WST-8) tests indicated cell toxicity. Increased mitochondrial activity was found for the submicron powders: incubation with high amounts revealed up to a threefold increase of osteoblast activity (ALP-activity). An overgrowth of the formed mineralized phase with phenotypical MG-63 cells was found by staining only for the submicron glasses. A distance ring is formed for the as-received powder. Superior bioactivity markers are found for shorter process times, that is, lower mass specific surface areas. This is attributed to the formation of carbonates during the comminution process. © 2013 Wiley Periodicals, Inc.
Keywords: in vitro bioactivity and biocompatibility; MG-63 cells; sub-micron particles; top-down production

Biocompatible ceramic-biopolymer coatings obtained by electrophoretic deposition on electron beam structured titanium alloy surfaces - Ramskogler, C.; Cordero, Luis; Warchomicka, F.; Boccaccini, Aldo R.; Sommitsch, C. (Materials Science Forum, 2017)
An area of major interest in biomedical engineering is currently the development of improved materials for medical implants. Research efforts are being focused on the investigation of surface modification methods for metallic prostheses due to the fundamental bioinert character of these materials and the possible ion release from their surfaces, which could potentially induce the interfacial loosening of devices after implantation. Electron beam (EB) structuring is a novel technique to control the surface topography in metals. Electrophoretic deposition (EPD) offers the feasibility to deposit at room temperature a variety of materials on conductive substrates from colloidal suspensions under electric fields. In this work single layers of chitosan composite coatings containing titania nanoparticles (n-TiO2) were deposit by EPD on electron beam (EB) structured Ti6Al4V titanium alloy. Surface structures were designed following different criteria in order to develop specific topography on the Ti6Al4V substrate. n-TiO2 particles were used as a model particle in order to demonstrate the versatility of the proposed technique for achieving homogenous chitosan based coatings on structured surfaces. A linear relation between EPD time and deposition yield on different patterned Ti6Al4V surfaces was determined under constant voltage conditions, obtaining homogeneous EPD coatings which replicate the 3D structure (pattern) of the substrate surface. The present results show that a combination of both techniques can be considered a promising surface modification approach for metallic implants, which should lead to improved interaction between the implant surface and the biological environment for orthopaedic applications.
CRIS-Team Scopus Importer:2022-08-05
Keywords: Electron beam structuring; Electrophoretic deposition; N-TiO2/chitosan; Ti6Al4V

Biocompatible colloidal feedstock for material extrusion processing of bioceramic-based scaffolds - Ferrández-Montero, A.; Ortega-Columbrans, P.; Eguiluz, A.; Sanchez-Herencia, A. J.; Detsch, Rainer; Boccaccini, Aldo R.; Ferrari, B. (Polymer Composites, 2024)
Nowadays an enormous effort has been made to impulse the incorporation of additive manufacturing (AM) approaches in the biomedical sector. One of the most recognized biomaterials for this end is bioceramics such as hydroxyapatite (HA), but unfortunately, ceramics present a lack of accessible technologies based on AM. Consequently, the development of new methodologies which enable the manufacture of bioceramic-based scaffolds is imperative. A large number of publications on polymer–ceramic composite processed by Material Extrusion are available, so far, the maximum ceramic loading reached is still a parameter to improve. Recently an alternative colloidal processing technique to prepare ceramic-based composite feedstock for material extrusion has been proposed. It has been demonstrated that tailoring the surface of the ceramic particles enables the processing of high ceramic loading composites by AM. This article shows the potential of the colloidal approach to process biocompatible PLA/HA feedstock increasing the homogeneity of the bioceramic phase into the composite. The feedstock characterization shows that HA surface modification makes possible the successful dispersion and the ceramic load increase without modifying the biocompatibility. The ceramic load increase does not modify the melting properties of the polymeric matrix required for the 3D printing process. This methodology allows for the first time the development of a final 3D printed composite structure with contents up to 72 wt% of HA by Material Extrusion. This colloidal approach paves the way to transfer the use of additive manufacturing techniques mainly devoted to polymeric biomaterials to other types of biomaterials such as bioceramics. Highlights: A colloidal approach for 3D printing of PLA/HA composites is proposed. HA surface modification made possible a load increase with high dispersion. The characterization of a PLA/HA feedstock for 3D printing is established. Biocompatible PLA/HA feedstock is processed by AM in customized structures. Colloidal approach allows the processing of 3D structures with 72 wt% of HA.
CRIS-Team Scopus Importer:2024-06-14
Keywords: additive manufacturing; biomaterials; colloidal processing; feedstock; surface modification

Biocompatible, Flexible Strain Sensor Fabricated with Polydopamine-Coated Nanocomposites of Nitrile Rubber and Carbon Black - Qu, Muchao; Qin, Yijing; SUN, YANYAN; Xu, Huagen; Schubert, Dirk W.; Zheng, Kai; Xu, Wei; Nilsson, Fritjof (ACS Applied Materials and Interfaces, 2020)
A flexible, biocompatible, nitrile butadiene rubber (NBR)-based strain sensor with high stretchability, good sensitivity, and excellent repeatability is presented for the first time. Carbon black (CB) particles were embedded into an NBR matrix via a dissolving-coating technique, and the obtained NBR/CB composite was coated with polydopamine (PDA) to preserve the CB layer. The mechanical properties of the NBR films were found to be significantly improved with the addition of CB and PDA, and the produced composite films were noncytotoxic and highly biocompatible. Strain-sensing tests showed that the uncoated CB/NBR films possess a high sensing range (strain of similar to 550%) and good sensitivity (gauge factor of 52.2), whereas the PDA/NBR/CB films show a somewhat reduced sensing range (strain of similar to 180%) but significantly improved sensitivity (gauge factor of 346). The hysteresis curves obtained from cyclic strain-sensing tests demonstrate the prominent robustness of the sensor material. Three novel equations were developed to accurately describe the uniaxial and cyclic strain-sensing behavior observed for the investigated strain sensors. Gloves and knee/elbow covers were produced from the films, revealing that the signals generated by different finger, elbow, and knee movements are easily distinguishable, thus confirming that the PDA/NBR/CB composite films can be used in a wide range of wearable strain sensor applications.
CRIS-Team WoS Importer:2020-10-16

Biodegradabiliy of spherical mesoporous silica particles (MCM-41) in simulated body fluid (SBF) - Boccardi, Elena; Philippart, Anahi; Beltran, Ana M.; Schmidt, Jochen; Liverani, Liliana; Peukert, Wolfgang; Boccaccini, Aldo R. (American Mineralogist, 2018)
Keywords: Mesoporous silica particles; Simulated body fluid; Bone tissue engineering; Drug carriers; Biomaterials - Mineralogy Meets Medicine; Biodegradability

Biodegradable and bioactive polymer/inorganic phase composites - Kuth, Sonja; Liverani, Liliana (Elsevier, 2021)
In this chapter an overview of the main properties that could be tailored in composites for tissue engineering scaffolds applications are reported. The main approaches have been reviewed and developed for the fabrication of composites to introduce gradients and enhance bioactivity, mechanical properties, and interface tissue response in scaffolds. Moreover, an overview of the commonly used scaffold fabrication techniques used for composites and some selected applications of composite scaffolds are also presented.
CRIS-Team Scopus Importer:2024-12-16
Keywords: Bioactivity; Biodegradation; Composites

Biodegradable and bioactive polymer/inorganic phase nanocomposites for bone tissue engineering (BTE) - Miguez-Pacheco, Valentina; Misra, S. K.; Boccaccini, Aldo R. (Elsevier Inc., 2014)
Scaffolds for bone tissue engineering (BTE) must be mechanically competent and chemically compatible with bone tissue to repair defects. Polymeric materials exhibit suitable mechanical and processing abilities but lack the bioactivity of inorganic ceramics. Composites of these materials are being developed to combine and improve their properties. It has become evident that cells respond to the topography of the surrounding extracellular matrix, specifically to nano-sized features; and reproducing these physical characteristics on the surface of scaffolds improves cell spread and attachment. Electrospinning can produce thin fibres with wide-ranging diameters and offers the possibility of fabricating nanocomposite fibrous scaffolds. This chapter focuses on ascertaining the impact of an inorganic phase on the mechanical properties, bioactivity and cell behaviour of electrospun composite structures.
CRIS-Team Scopus Importer:2022-08-05
Keywords: Bioactivity; Bone scaffolds; Electrospinning; Nanocomposites

Biodegradable nanostructures: Degradation process and biocompatibility of iron oxide nanostructured arrays - Yang, Yuyun; Zhou, Juncen; Detsch, Rainer; Taccardi, Nicola; Heise, Svenja; Virtanen, Sannakaisa; Boccaccini, Aldo R. (Materials Science and Engineering C, 2018)

Biodegradable poly(glycerol sebacate)/poly(3-hydroxybutyrate)-TiO2 nanocomposites: fabrication and characterisation - Roether, Judith; Rai, Ranjana; Wolf, R.; Tallawi, Marwa; Boccaccini, Aldo R. (Materials Science and Technology, 2014)
Novel Nanocomposite films containing TiO2 nanoparticles incorporated in blend matrices of biocompatible and bioresorbable polymers, namely poly(glycerol sebacate) (PGS) and poly(3-hydroxybutyrate) P(3HB), were developed. The samples were fabricated via a sequential step of solvent casting followed by cross-linking. PGS/P(3HB) blends (controls) were fabricated in two different ratios, i.e. 7 : 1 and 8 : 1. Varying amounts of TiO2 nanoparticles (1 and 2 vol.-%) were incorporated into the matrices. SEM studies revealed that the TiO2 particles were distributed both within the matrix and on the surface of the films thus imparting surface nanotopography and increasing the surface roughness. These microstructural features combined with the cumulative effect of blending of the two polymeric systems influenced the wettability, chemical and mechanical properties of the films. In vitro degradation of the fabricated matrices in PBS medium over a 30 day period confirmed that the composites undergo weight loss and mechanical, chemical and surface topography changes. The nanocomposites constitute model biodegradable organic-inorganic systems suitable for tissue engineering applications.
Keywords: Nanocomposite; TiO2; Nanoparticles; Poly(glycerol sebacate); Poly(3-hydroxybutyrate)

Biodegradable Polylactide Supraparticle Powders with Functional Additives for Biomedical Additive Manufacturing - Canziani, Herbert; Hanschmann, Benedikt; Tischer, Florentin; Sommereyns, Alexander; Distler, Thomas; Schramm, Jonas; Hesse, Nicolas; Schmidt, Jochen; Grünewald, Alina; Detsch, Rainer; Boccaccini, Aldo R.; Maskos, Michael; et al. (Advanced Functional Materials, 2022)
Additive manufacturing, in particular powder bed-based fabrication processes hold promise to revolutionize biomedical engineering for the ability to provide customized, functional implants, for example as bone replacement materials. However, providing functional powder particles that unify material requirements for biodegradable and bioactive biomaterials and process requirements to enable successful powder bed fusion remains an unmet challenge. Here, a supraparticle-based approach to create biodegradable poly(lactic acid) and composite powders for the additive manufacturing of bone replacement materials is introduced. Colloidal binary Ca-SiO2 glasses and hydroxyapatite are incorporated as bioactive functional additives to support the formation of bone-like calcium phosphate. The supraparticle powders are prepared by a scalable spray-drying process, which offers control of particle size, shape, and composition. All process-relevant powder characteristics are analyzed as a function of composition and structure, including flowability, thermal, and melt rheological properties. The optimized supraparticle powders are successfully used in the process of laser powder bed fusion of polymers to prepare macroscopic specimens via additive manufacturing. It is demonstrated that the material combination of the composites provides relevant functional properties, including biodegradation and bioactivity. The process provides a flexible and adjustable toolbox for the design of functional powders toward biomedical additive manufacturing.<br
Keywords: 3D printing; additive manufacturing; biomaterials; PLA; powder bed fusion; spray drying; supraparticles

Biodegradable polymer coated 45S5 Bioglass-derived glass-ceramic scaffolds for bone tissue engineering - Boccaccini, Aldo R.; et al. (Glass Technology, 2007)
Three-dimensional, highly porous foam-like composite scaffolds were fabricated by coating 45S5 Bioglass-derived glass-ceramic foams with a biodegradable poly-(3-hydroxybutyrate) (PHB) layer. The PHB was produced by bacteria isolation, using afermentation process. The glass-ceramic scaffolds were fabricated by the replication technique using 45S5 Bioglass powder. The sintering process was optimised in order to increase the mechanical strength of the foam scaffolds. During sintering, the glass crystallises, forming a mixed sodium calcium silicate (Na2Ca2Si3O 9) phase. The microstructure of the composite scaffolds was analysed by scanning electron microscopy and x-ray diffraction. The polymer coating did not affect the interconnectivity of the pore structure. The compressive strength of the coated and uncoated scaffolds was measured and it was found that the polymer coating considerably increased the compressive strength of the scaffolds. Bioactivity was studied by soaking the samples in a simulated body fluid (SBF) to assess the formation of hydroxy apatite (HA) crystals on the scaffolds' surfaces. It was found that these novel composite scaffolds are highly bioactive, as after two weeks of immersion in SBF, a uniform layer of HA crystals was formed. The novel Bioglass/PHB composite foams are promising candidates for bone tissue engineering scaffolds.
UnivIS-Import:2015-03-09:Pub.2007.tech.IW.LM.biodeg

Biodegradable Polymer Matrix Composites Containing Graphene-Related Materials for Antibacterial Applications: A Critical Review - Avcu, Egemen; Bastan, Fatih E.; Guney, Mert; Yildiran Avcu, Yasemin; Ur Rehman, Muhammad A.; Boccaccini, Aldo R. (Acta Biomaterialia, 2022)
For the first time, the present review critically evaluates biodegradable polymer matrix composites containing graphene-related materials (GRMs) for antibacterial applications while discussing their development, processing routes, mechanical properties, and antibacterial activity. Due to its suitable biological properties and processability, chitosan has been the most widely used biodegradable polymer for the fabrication of GRM-containing composites with antibacterial properties. The majority of biodegradable polymers (including cellulose-, gelatine-, PVA-, PCL-, and PHA-based polymers) exhibit little to no antibacterial effect alone; however, they show significant antibacterial activity (>70%) when combined with GRMs. In vitro and in vivo studies indicate that GRMs functionalization with biodegradable polymers also reduces potential GRM cytotoxicity. Overall, GRMs in biodegradable polymer matrices provide attractive antibacterial activity against a broad spectrum of bacteria (>30 different bacteria) along with improved mechanical properties over pristine polymers, where the type and the degree of improvement provided by GRMs depend on the specific matrix. For example, the addition of GRMs into chitosan, PVA, and PCL matrices increases their tensile strength by 80%, 180%, and 40%, respectively. Challenges remain in understanding the effects of processing routes and post-processing methods on the antibacterial activity and biocompatibility of biodegradable polymer/GRM composites. Given their promising properties and functionality, research on these composites is expected to further increase along with the implementation of new composite systems. These would include a wide range of applications, e.g., wound dressings, tissue engineering, drug delivery, biosensing, and photo-thermal therapy, as well as non-medical use, e.g., antibacterial food packaging, water treatment, and antibacterial fabrics. Statement of significance: Graphene-related materials (GRMs) in polymer matrices can provide excellent antibacterial activity against a broad spectrum of bacteria together with improved mechanical properties (e.g., tensile strength and elastic modulus) over pristine polymers; thus, research efforts and applications of biodegradable polymer matrix composites containing GRMs have increased notably in the last ten years. For the first time, the present review critically evaluates biodegradable polymer matrix composites containing GRMs for antibacterial applications while discussing their development, processing routes, mechanical properties, and antibacterial activity. Future research directions for each composite system are proposed to shed light on overcoming the existing challenges in composite performance (e.g., mechanical properties, toxicity) reported in the literature.
CRIS-Team Scopus Importer:2022-09-02
Keywords: Bactericide; Cellulose; Chitosan; GO (Graphene oxide); PVA (Polyvinyl alcohol)

Bioengineered 3D ovarian model for long-term multiple development of preantral follicle: bridging the gap for poly(ε-caprolactone) (PCL)-based scaffold reproductive applications - Di Berardino, Chiara; Peserico, Alessia; Camerano Spelta Rapini, Chiara; Liverani, Liliana; Capacchietti, Giulia; Russo, Valentina; Berardinelli, Paolo; Ünalan, Irem; Damian-Buda, Andrada-Ioana; Boccaccini, Aldo R.; Barboni, Barbara (Reproductive Biology and Endocrinology, 2024)
Background: Assisted Reproductive Technologies (ARTs) have been validated in human and animal to solve reproductive problems such as infertility, aging, genetic selection/amplification and diseases. The persistent gap in ART biomedical applications lies in recapitulating the early stage of ovarian folliculogenesis, thus providing protocols to drive the large reserve of immature follicles towards the gonadotropin-dependent phase. Tissue engineering is becoming a concrete solution to potentially recapitulate ovarian structure, mostly relying on the use of autologous early follicles on natural or synthetic scaffolds. Based on these premises, the present study has been designed to validate the use of the ovarian bioinspired patterned electrospun fibrous scaffolds fabricated with poly(ε-caprolactone) (PCL) for multiple preantral (PA) follicle development. Methods: PA follicles isolated from lamb ovaries were cultured on PCL scaffold adopting a validated single-follicle protocol (Ctrl) or simulating a multiple-follicle condition by reproducing an artificial ovary engrafted with 5 or 10 PA (AO5PA and AO10PA). The incubations were protracted for 14 and 18 days before assessing scaffold-based microenvironment suitability to assist in vitro folliculogenesis (ivF) and oogenesis at morphological and functional level. Results: The ivF outcomes demonstrated that PCL-scaffolds generate an appropriate biomimetic ovarian microenvironment supporting the transition of multiple PA follicles towards early antral (EA) stage by supporting follicle growth and steroidogenic activation. PCL-multiple bioengineering ivF (AO10PA) performed in long term generated, in addition, the greatest percentage of highly specialized gametes by enhancing meiotic competence, large chromatin remodeling and parthenogenetic developmental competence. Conclusions: The study showcased the proof of concept for a next-generation ART use of PCL-patterned scaffold aimed to generate transplantable artificial ovary engrafted with autologous early-stage follicles or to advance ivF technologies holding a 3D bioinspired matrix promoting a physiological long-term multiple PA follicle protocol.
CRIS-Team Scopus Importer:2024-08-16
Keywords: in vitro folliculogenesis; in vitro oogenesis; Tissue engineering; Artificial-ovary; Preantral follicle development; Large chromatin remodeling; Oocyte maturation; Parthenogenetic activation; Embryo development; PCL-electrospun scaffold

Biofabrication and Characterization of Alginate Dialdehyde-Gelatin Microcapsules Incorporating Bioactive Glass for Cell Delivery Application - Reakasame, Supachai; Jin, Anbang; Zheng, Kai; Qu, Muchao; Boccaccini, Aldo R. (Macromolecular Bioscience, 2020)
The effect of the incorporation of 45S5 bioactive glass (BG) microparticles (mean particle size ≈ 2 µm) on the fabrication and physicochemical properties of alginate dialdehyde-gelatin hydrogel capsules is investigated. The addition of BG particles decreases the hydrogel gelation time by ≈79% and 91% for the samples containing 0.1% w/v and 0.5% w/v BG, respectively. Moreover, it results in increasing average diameter of hydrogel capsules produced via a pressure-driven extrusion technique from about 1000 µm for the samples without BG to about 1700 and 1900 µm for the samples containing BG at concentrations of 0.1% w/v and 0.5% w/v, respectively. The presence of BG particles in the capsules decreases the degradation rate and improves the bioactivity of the materials. The viability of MG-63 cells encapsulated in all samples increases during the first 7 d of cultivation and maintains the same level during 21 d of cultivation. The early cell viability in samples containing BG is lower than that in samples without BG. The results show that 45S5 BG can positively regulate the osteogenic activity of cells incorporated in hydrogel capsules. The fabricated composite capsules exhibit promising potential for cell delivery in bone regeneration applications.
CRIS-Team Scopus Importer:2020-09-11
Keywords: bioactive glass; bone cells; cell encapsulation; microcapsules; oxidized alginate

Biofabrication: new approaches for tissue regeneration - Horch, Raymund E.; Weigand, Annika; Wajant, Harald; Groll, Juergen; Boccaccini, Aldo R.; Arkudas, Andreas (Handchirurgie, Mikrochirurgie, Plastische Chirurgie, 2018)
The advent of Tissue Engineering (TE) in the early 1990ies was fostered by the increasing need for functional tissue and organ replacement. Classical TE was based on the combination of carrier matrices, cells and growth factors to reconstitute lost or damaged tissue and organs. Despite considerable results in vitro and in experimental settings the lack of early vascularization has hampered its translation into daily clinical practice so far. A new field of research, called "biofabrication" utilizing latest 3D printing technologies aims at hierarchically and spatially incorporating different cells, biomaterials and molecules into a matrix to alleviate a directed maturation of artificial tissue. A literature research of the relevant publications regarding biofabrication and bioprinting was performed using the PubMed data base. Relevant papers were selected and evaluated with secondary analysis of specific citations on the bioprinting techniques. 180 relevant papers containing the key words were identified and evaluated. Basic principles into the developing field of bioprinting technology could be discerned. Key elements comprise the high-throughput assembly of cells and the fabrication of complex and functional hierarchically organized tissue constructs. Five relevant technological principles for bioprinting were identified, such as stereolithography, extrusion-based printing, laser-assisted printing, inkjet-based printing and nano-bioprinting. The different technical methods of 3D printing were found to be associated with various positive but also negative effects on cells and proteins during the printing process. Research efforts in this field obviously aim towards the development of optimizing the so called bioinks and the printing technologies. This review details the evolution of the classical methods of TE in Regenerative Medicine into the evolving field of biofabrication by bioprinting. The advantages of 3D bioprinting over traditional tissue engineering techniques are based on the assembling of cells, biomaterials and biomolecules in a spatially controlled manner to reproduce native tissue macro-, micro- and nanoarchitectures, that can be utilized not only to potentially produce functional replacement tissues or organs but also to serve as new models for basic research. Mimicking the stromal microenvironment of tumor cells to study the process of tumor formation and progression, metastasis, angiogenesis and modulation of the associated processes is one of these applications under research. To this end a close collaboration of specialists from the fields of engineering, biomaterial science, cell biology and reconstructive microsurgery will be necessary to develop future strategies that can overcome current limitations of tissue generation. BACKGROUND MATERIALS AND METHODS RESULTS CONCLUSION

Biofabrication of 3D Alginate-Based Hydrogel for Cancer Research: Comparison of Cell Spreading, Viability, and Adhesion Characteristics of Colorectal HCT116 Tumor Cells - Ivanovska, Jelena; Zehnder, Tobias; Lennert, Pablo; Sarker, Bapi; Boccaccini, Aldo R.; Hartmann, Arndt; Schneider-Stock, Regine; Detsch, Rainer (Tissue Engineering - Part C: Methods, 2016)
Hydrogels are an important class of biomaterials as they could mimic the extracellular matrix (ECM). Among the naturally occurring biopolymers, alginate and gelatin are extensively used for many biomedical applications. For developing biofabrication constructs as three-dimensional (3D) cell culture models, realistic imaging of cell spreading and proliferation inside the hydrogels represents a major challenge. Therefore, we aimed to establish a system that can mimic the structural architecture, composition, and biological functions of the ECM for cancer research approaches. For this, we compared the cell behavior of human colon cancer HCT116 cells in two biofabricated hydrogels as follows: pure alginate and cross-linked alginate-gelatin (ADA-GEL) matrixes. Our data indicate that cells from the ADA-GEL matrix showed highest proliferation and cellular networks through the material. Analyzing the mRNA expression of several integrins of cells cultured inside of the matrix, we showed that mRNA expression of integrin subunits differed based on the cell focal adhesion characteristics. Furthermore, we showed that recultured ADA-GEL immobilized cells do not differ from parental HCT116 cells regarding migration and proliferation capabilities. Comparing adhesion and other phenotypic characteristics of HCT116 tumor cells, we suggest that ADA-GEL hydrogel is a more suitable 3D system than pure alginate and seems to optimally mimic the physiological behavior of the tumor microenvironment. For the first time, we present a functional 3D hydrogel construct for colon cancer cells, which are supporting their physiological cell attachment, spreading, and viability. We strongly believe that it will be applicable as a suitable in vitro 3D tumor model to study different aspects of tumor cell behavior.
EVALuna2:6830

Biofabrication of a co-culture system in an osteoid-like hydrogel matrix - Zehnder, Tobias; Boccaccini, Aldo R.; Detsch, Rainer (Biofabrication, 2017)
Keywords: alginate dialdehyde/gelatin hydrogel; biofabrication; bioplotting; osteoblast/osteoclast co-culture system; osteoid bone phase

Biofabrication of vessel grafts based on natural hydrogels - Cicha, Iwona; Detsch, Rainer; Singh, Raminder; Reakasame, Supachai; Alexiou, Christoph; Boccaccini, Aldo R. (Current Opinion in Biomedical Engineering, 2017)

Biofabrication of vessel-like structures with alginate di-aldehyde-gelatin (ADA-GEL) bioink. - Ruther, Florian; Distler, Thomas; Boccaccini, Aldo R.; Detsch, Rainer (Journal of Materials Science: Materials in Medicine, 2018)
One of the key challenges in the field of blood vessel engineering is the in vitro production of small and large diameter vessels. Considering that a combination of alginate di-aldehyde and gelatin (ADA-GEL) has been successfully applied for different biofabrication approaches, the aim of this study was to exploit ADA-GEL for the fabrication of vessel structures with diameters up to 4 mm. To explore plotting possibilities and to study the swelling behaviour, a library of vessel-like constructs with different diameters made from 2, 3 and 4% (w/v) alginate was created by using various hand-crafted double-needle extrusion systems. Vessel diameters were varied through changes of the double-needle core and outer diameters. A straightforward model for the production of vessel of different diameters from a variety of double-needle systems was established and vessel-constructs with diameters of up to 3.7 mm could be created. It was successfully demonstrated that an artificial vessel, consisting of an outer layer of 7.5% ADA50-GEL50 and an inner core of 3% gelatin, can support the proliferation and migration of an immobilized co-culture containing fibroblast (NHDF) and endothelial (HUVEC) cells. The openness and tightness of the hollow ADA-GEL structures were further confirmed by a dye injection test. Nanoindentation was performed to determine the Young's modulus of the used materials. Cell vitality was proved after 1, 2 and 3 weeks of incubation. The results showed a nearly twofold increase of viable cells per week. Fluorescent images confirmed cell migration during the whole incubation time.

Biofabrication of vessel-like structures with alginate di-aldehyde—gelatin (ADA-GEL) bioink - Ruther, Florian; Distler, Thomas; Boccaccini, Aldo R.; Detsch, Rainer (Journal of Materials Science: Materials in Medicine, 2019)

Biofabrikation von Hydrogelkonstrukten auf Basis von Alginat und hybriden Gerüststrukturen für die Gewebezüchtung - Zehnder, Tobias (2017)
Biofabrication encompasses the use of additive manufacturing (AM) techniques, biomaterials (hydrogels), cells and bioactive substances for tissue engineering or as 3D tissue models for drug-screening studies or for tumor research. Characteristic for biofabrication approaches is the exploitation of the freedom of design provided by AM techniques enabling the fabrication of defined, complex 3D structures together with the processing of hydrogel/cell mixtures, so called bioinks. This approach enables the defined positioning of different cell types and biomaterials in predefined positions of a construct and thus biofabrication appears as an important novel technology in the general field of tissue engineering and for investigating tumour development in 3D matrices.In the present work, a biofabrication approach has been established using bioplotting and fused deposition modelling for the fabrication of 3D structures from a crosslinked hydrogel, termed ADA-GEL, based on alginate di-aldehyde (ADA) gelatine (GEL) crosslinked hydrogel (ADA-GEL) together with different bone tissue related cell types.It was shown that the ADA-GEL hydrogel is compatible with the bioplotting technique. Different parameters of the bioplotting process, namely speed, pressure and needle diameter were assessed regarding their interactions, their influence on the geometry of the created structure as well as on the viability of the immobilised cells in the bioink. In this way, a process chain was established which enables the fabrication of bioplotted ADA-GEL constructs with defined geometry. Moreover, the degradation behaviour and the mechanical properties of different modifications of the ADA-GEL system were evaluated. The stock solution concentrations of ADA and GEL as well as the molecular weight of the ADA-component were varied. It was revealed that ADA-GEL hydrogel degraded by the release of GEL and that the stiffness of the constructs decreased with ongoing incubation time depending on the used composition. Based on these results different cell types were used together with ADA-GEL as bioink and the cell development in bioplotted ADA-GEL constructs was assessed over incubation times of several weeks. MG-63 osteoblast like cells were used and it was shown that MG-63 cells proliferated in ADA-GEL constructs and covered the whole structure after 28 days of incubation. Furthermore, bone marrow derived stromal cells ST2 were used as a cell model and it was shown that proliferation of ST2 cells could be dictated by the molecular weight of the ADA component and the stock solution concentrations of ADA and GEL. An elevated degradation of the ADA-GEL matrix showed faster cell proliferation. In a further approach, a co-culture of ST2 and osteoclast progenitor cells RAW 264.7 was used in an ADA-GEL modification with similar mechanical properties as the unmineralised osteoid bone phase. In this set-up, the interaction of the cell types in comparison to single cultures was investigated, revealing increased osteopontin expression and release of vascular endothelial growth factor (VEGF) in the co-culture group.A sequential bioplotting process was used to create hybrid structures to overcome the limited mechanical properties of the ADA-GEL regarding application in bone tissue engineering. The hybrid constructs consist of ADA-GEL with immobilised ST2 cells and a phase of polycaprolactone/polyethyleneglycol (PCL/PEG) blend, which showed superior properties regarding ST2 cell adhesion in comparison to pure PCL. The PCL/PEG phase acts as a support structure in the hybrid constructs and so enhances the mechanical properties in comparison to the pure hydrogel phase to a range, which is comparable with natural bone. Altogether, the ADA-GEL hydrogel system is a very promising material for use in biofabrication.; Bei der Biofabrikation kommen Generative Fertigungsverfahren, Biomaterialien (Hydrogele), Zellen und Wachstumsfaktoren zur Züchtung von Geweben, zur Herstellung von 3D Gewebemodellen für die Untersuchung von Wirkstoffen oder für die Tumorforschung zum Einsatz. Kennzeichnend für die Biofabrikation ist die Nutzung der Flexibilität, welche die Generativen Fertigungsverfahren hinsichtlich der Gestaltung bieten. Dadurch wird die Herstellung von komplexen 3-dimensionalen (3D) Strukturen ermöglicht, wobei Mischungen aus Hydrogelen und Zellen, sogenannte Biotinten als Prozessmaterial angewendet werden. Dieser Ansatz ermöglicht die kontrollierte Positionierung von verschiedenen Zellarten und Materialien in vordefinierten Positionen eines Konstrukts und daher erscheint die Biofabrikation als eine bedeutsame, neuartige Technologie für das Forschungsfeld der Gewebezüchtung sowie für die Erforschung der Tumorentwicklung in einer 3D Matrix.In der vorliegenden Arbeit wird ein Biofabrikationsprozess angewendet, welcher auf der Nutzung des Bioplottingverfahrens und der Technik des Fused Deposition Modellings zur Herstellung von 3D Konstrukten aus einem vernetzten Hydrogel, genannt ADA-GEL, zusammen mit verschiedenen für das Knochengewebe relevanten Zelltypen beruht. ADA-GEL Hydrogel basiert auf Alginat Dialdehyd (ADA) und Gelatine (GEL).Es konnte gezeigt werden, dass das ADA-GEL Hydrogel für den Einsatz im Bioplottingverfahren geeignet ist. Verschiedene Parameter des Bioplottingverfahrens, wie Geschwindigkeit, Druck und Nadeldurchmesser wurden hinsichtlich ihrer Wechselwirkungen, ihres Einflusses auf die Geometrie des erzeugten Konstruktes sowie auf die Vitalität der in der Biotinte immobilisierten Zellen untersucht. Auf diese Weise wurde eine Prozesskette etabliert, welche die Fabrikation von ADA-GEL Konstrukten mit definierter Geometrie unter Einsatz des Bioplottingverfahrens ermöglicht. Ferner wurden das Abbauverhalten und die mechanischen Eigenschaften verschiedener Modifikationen des ADA-GEL Hydrogels untersucht. Die Konzentration der ADA und GEL Stammlösungen sowie das Molekulargewicht des ADAs wurden variiert. Es wurde gezeigt, dass ADA-GEL unter Freisetzung von GEL degradiert und die Steifigkeit der Konstrukte mit zunehmender Inkubationszeit abnimmt, wobei dies von der ADA-GEL Modifikation abhängig ist. Basierend auf diesen Untersuchungen wurden verschiedene Zellarten zusammen mit ADA-GEL als Biotinten verwendet und die Zellentwicklung in den geplotteten ADA-GEL Konstrukten über Inkubationszeiten von mehreren Wochen untersucht. Osteoblasten ähnliche MG-63 Zellen wurden eingesetzt und es konnte gezeigt werden, dass MG-63 Zellen in den ADA-GEL Konstrukten proliferierten und nach einer Inkubationszeit von 28 Tagen die gesamte Struktur bedeckten. Des Weiteren wurden Stromazellen des Knochenmarks ST2 als Zellmodell verwendet. Es konnte gezeigt werden, dass die Proliferation der ST2 Zellen in Abhängigkeit des Molekulargewichts des ADAs und den Konzentrationen der Stammlösungen des ADAs und der GEL gesteuert werden konnte. Hierbei zeigten ADA-GEL Modifikationen mit einer höheren Abbaurate eine erhöhte Zellproliferation. Die ST2 Zellen wurden mit Osteoklasten Vorläuferzellen RAW 264.7 in einer Kokultur in ADA-GEL Konstrukten mit einer ähnlichen Steifigkeit wie sie die nicht mineralisierte Knochenmatrix, das so genannte Osteoid aufweist, kultiviert. Mittels dieses Aufbaus wurden Zellinteraktionen im Vergleich zu einzeln kultivierten Gruppen der beiden Zelltypen evaluiert, wobei deutlich wurde, dass in der Kokulturgruppe die Expression von Osteopontin sowie die Freisetzung des angiogenen Signalmoleküls VEGF erhöht war.Um die limitierten mechanischen Eigenschaften des ADA-GELs hinsichtlich dessen Verwendung in der Knochengewebezüchtung auszugleichen, wurde ein sequentielles Bioplottingverfahren eingesetzt um Hybridstrukturen zu erzeugen. Diese Hybridstrukturen bestehen aus ADA-GEL mit immobilisierten ST2 Zellen und einem Polycaprolacton/Polyethylenglycol (PCL/PEG) Blendmaterial, welches vorteilhafte Eigenschaften hinsichtlich der Zelladhäsion im Vergleich zu PCL zeigte. Die PCL/PEG Phase dient in den Hybridkonstrukten als Unterstützungsstruktur und erhöht so deren mechanische Eigenschaften im Vergleich zur reinen Hydrogelphase, sodass diese in einem vergleichbaren Bereich wie natürlicher Knochen liegen. Insgesamt konnte gezeigt werden, dass das ADA-GEL Hydrogelsystem ein sehr vielsprechendes Material für die Anwendung in der Biofabrikation ist.
Keywords: Alginate; Gelatine; 3D Printing; Hydrogel; Tissue Engineering; Biofabrication; Cell printing

Biofunctionalization of ADA-GEL Hydrogels Based on the Degree of Cross-Linking and Polymer Concentration Improves Angiogenesis - Heltmann-Meyer, Stefanie; Detsch, Rainer; Hazur, Jonas; Kling, Lasse; Pechmann, Sabrina; Kolan, Rajkumar Reddy; Osterloh, Justus; Boccaccini, Aldo R.; Christiansen, Silke; Geppert, Carol-Immanuel; Arkudas, Andreas; Horch, Raymund E.; et al. (Advanced Healthcare Materials, 2025)
The creation of bioartificial tissues is a promising option for the reconstruction of large-volume defects. The vascularization of tissue engineering constructs, as well as the material properties of the carrier matrix, are important factors for successful clinical application. In this regard, hydrogels are promising biomaterials, providing an extracellular matrix-like milieu that enables the possibility of cell transplantation and de novo tissue formation. Furthermore, biofunctionalization allows for a certain fine-tuning of angiogenic properties. This study aims to investigate vascularization and tissue formation of highly cross-linked alginate dialdehyde (ADA) and gelatin (GEL). This highly cross-linked network is created using a dural cross-linking mechanism combining ionic (Ca2+ ions) and enzymatic (human transglutaminase (hTG)) cross-linking, resulting in reduced swelling and moderate degradation rates. Vascularization of the ADA-GEL-hTG constructs is induced surgically using arteriovenous (AV) loops. Biocompatibility, tissue formation, and vascularization are analyzed by histology and X-ray microscopy. After only 2 weeks, vascularization of the ADA-GEL-hTG constructs is already present. After 4 weeks, both de novo tissue formation and vascularization of the ADA-GEL-hTG matrix increase. In conclusion, ADA-GEL-hTG-based hydrogels are shown to be promising scaffold materials for tissue engineering applications.
CRIS-Team Scopus Importer:2025-04-01
Keywords: ADA-GEL; angiogenesis; biofunctionalization; hydrogel; tissue engineering

Biofunctionalization of dispense-plotted hydroxyapatite scaffolds with peptides: Quantification and cellular response - Detsch, Rainer; et al. (Journal of Biomedical Materials Research Part A, 2010)
Hydroxyapatite (HA) ceramic is a widely used synthetic bone substitute material for the regeneration of bone defects. We manufactured HA scaffolds with adjustable pore sizes and pore geometry by dispense-plotting. In addition, we attached peptides covalently onto the HA surface and are able to simultaneously quantify the amount of covalently attached and adsorbed peptide down to the picomolar range with a novel fluorescence-based detection method. In cell culture assays with stromal bone marrow cells, we observed a positive effect of biofunctionalization on cell differentiation after 21 days of culture when comparing the scaffold functionalized with the RGD motif containing adhesion peptide to an unmodified scaffold. © 2009 Wiley Periodicals, Inc.
Keywords: Biofunctionalization; Bone marrow cells; Bone substitute; Hydroxyapatite; Osteoblastic differentiation; Rapid prototyping

Bioglass®-based scaffolds incorporating polycaprolactone and chitosan coatings for controlled vancomycin delivery - Yao, Qingqing; Nooeaid, Patcharakamon; Roether, Judith; Dong, Yanining; Zhang, Qiqing; Boccaccini, Aldo R. (Ceramics International, 2013)
Highly porous scaffolds have been fabricated by the replication technique using 45S5 Bioglass® (BG) powder. For the purpose of imparting a local drug release capability, the scaffolds were coated with polycaprolactone and vancomycin-loaded chitosan by a two-step procedure. Bare BG scaffolds loaded with vancomycin via a direct immersion method were used as control. The chemical composition and microstructure of bare and coated scaffolds were characterized through Fourier-transform infrared (FTIR) spectroscopy and scanning electron microscopy (SEM), respectively. The mechanical properties of the coated scaffolds were significantly improved compared with uncoated scaffolds; the compressive strength values of the coated scaffolds were about 3 times and the area under the stress-strain curve was about 7 times higher than those of the uncoated scaffolds. The scaffolds degradation behavior and the drug release profiles were studied in a phosphate buffered saline (PBS) solution. There was a sharp release of the drug in the first few hours (8 h) for both bare and coated scaffolds. For the bare scaffolds the drug was released completely in 24 h. However, the coated scaffolds showed a sustained release in a period of 11 days, suggesting the potential of the present polymer coated BG scaffolds to be used as bone tissue scaffolds with drug carrier and delivery ability. © 2013 Elsevier Ltd and Techna Group S.r.l.
UnivIS-Import:2015-03-09:Pub.2013.tech.IW.LM.biogla
Keywords: Bioactive glass; Drug delivery; Scaffolds; Tissue engineering

Bioglass-based scaffolds with carbon nanotube coating for bone tissue engineering. - Meng, Decheng; Ioannou, John; Boccaccini, Aldo R. (Journal of Materials Science: Materials in Medicine, 2009)
Highly porous 45S5 Bioglass®-based foam scaffolds were coated with multi-walled carbon nanotubes (CNT) by electrophoretic deposition (EPD) technique. By placing the scaffolds in between the two electrodes of the EPD cell, a CNT coating of up to 1 μm thickness was achieved on the surface throughout the whole three dimensional (3D) matrix. A 0.5 wt% CNT aqueous suspension was used and EPD was carried out at 2.8 V for 10 mins. The compression strength of this CNT/Bioglass® composite was measured to be 0.70 MPa. Moreover the increased electrical conductivity of the composite with CNT coating was confirmed. The scaffolds have the potential for applications in bone tissue engineering due to the high bioactivity, nano-roughness in 3D and electrical conductivity provided by the addition of CNT. © 2009 Springer Science+Business Media, LLC.
UnivIS-Import:2015-03-09:Pub.2009.tech.IW.LM.biogla

Bioglass®/chitosan-polycaprolactone bilayered composite scaffolds intended for osteochondral tissue engineering - Yao, Qingqing; Nooeaid, Patcharakamon; Detsch, Rainer; Roether, Judith; Dong, Yanming; Goudouri, Ourania Menti; Schubert, Dirk W.; Boccaccini, Aldo R. (Journal of Biomedical Materials Research Part A, 2014)
Polymer-coated 45S5 Bioglass® (BG)/chitosan-polycaprolactone (BG/CS-PCL) bilayered composite scaffolds were prepared via foam replication and freeze-drying techniques for application in osteochondral tissue engineering. The CSPCL coated and uncoated BG scaffolds were characterized by X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy and scanning electron microscopy (SEM). The mechanical properties of the coated scaffolds were significantly improved in comparison to uncoated scaffolds. The bioactivity and biodegradation behavior of scaffolds were studied in simulated body fluid (SBF) for up to 28 days. The interface between the BG scaffold and the polymer coating layer was observed by SEM and a suitable interpenetration of the polymer into the scaffold struts was found. The effects of coated and uncoated BG scaffolds on MG-63 osteoblastlike cells were evaluated by cell viability, adhesion and proliferation.
Keywords: Bilayered scaffolds; Bioglass®; Chitosan; Osteochondral tissue engineering; Polycaprolactone

Bioglass-derived glass-ceramic scaffolds: study of cell proliferation and scaffold degradation in vitro - Chen, Q. Z.; Efthymiou, A.; Salih, V.; Boccaccini, Aldo R. (Journal of Biomedical Materials Research Part A, 2008)
Cell support function as well as cell proliferation on highly porous Bioglass®-derived glass-ceramic scaffolds (designed for bone tissue engineering) have been assessed in vitro using osteoblast-like cells (MG 63) cultured for up to 6 days. The biodegradation and mechanical stability of the scaffolds in the cell-culture medium have also been investigated. It was found that the scaffolds had excellent cell supporting ability, with cells effectively infiltrating into and surviving at the center of the scaffolds. A quantitative study using the AlamarBlue™ assay revealed that the proliferation of cells on the glass-ceramic materials was comparable to that on the noncrystallized Bioglass®. While the crystalline phase in the glass-ceramic scaffolds transformed into a biodegradable amorphous calcium phosphate phase during cell culture, the mechanical strength of the scaffolds was maintained when compared with that of scaffolds incubated in simulated body fluid or immersed in cell-free culture medium. It is believed that the attached cells and collagen secreted by cells could fill the micropores and microcracks on the surface of the foam struts, thus contributing to the mechanical stability of the degrading scaffolds. In summary, the developed glass-ceramic scaffolds possess the most essential features of a scaffold for bone tissue engineering: they are capable to support and foster relevant cells, able to provide temporary mechanical function, and biodegradable. © 2007 Wiley Periodicals, Inc.
UnivIS-Import:2015-03-09:Pub.2008.tech.IW.LM.biogla
Keywords: Bioactivity; Bioglass®; In vitro; Osteoblasts; Scaffolds; Tissue engineering

Biological effects of a zinc-substituted borosilicate bioactive glass on human bone marrow derived stromal cells in vitro and in a critical-size femoral defect model in rats in vivo - Saur, M.; Kunisch, E.; Fiehn, L. A.; Arango Ospina, Marcela; Merle, C.; Hagmann, S.; Moghaddam, A.; Stiller, A.; Hupa, L.; Renkawitz, T.; Kaňková, H.; Galusková, D.; et al. (Biomaterials Science, 2024)
The borosilicate 0106-B1-bioactive glass (BG) composition (in wt%: 37.5 SiO2, 22.6 CaO, 5.9 Na2O, 4.0P2O5, 12.0 K2O, 5.5 MgO, 12.5 B2O3) has shown favorable processing characteristics and bone regeneration ability. This study investigated the addition of zinc (Zn) to 0106-B1-BG as an approach to improve this BG's biological properties. Different proportions of ZnO were substituted for CaO in 0106-B1-BG, resulting in three new BG-compositions: 1-Zn-BG, 2-Zn-BG, 3-Zn-BG (in wt%: 37.5 SiO2, 21.6/20.1/17.6 CaO, 4.0 P2O5, 5.9 Na2O, 12.0 K2O, 5.5 MgO, 12.5 B2O3 and 1.0/2.5/5.0 ZnO). Effects of the BG compositions on cytocompatibility, osteogenic differentiation, extracellular matrix deposition, and angiogenic response of human bone marrow-derived mesenchymal stromal cells (BMSCs) were evaluated in vitro. Angiogenic effects were assessed using a tube formation assay containing human umbilical vein endothelial cells. The in vivo osteogenic and angiogenic potentials of 3-Zn-BG were investigated in comparison to the Zn-free 0106-B1-BG in a rodent critical-size femoral defect model. The osteogenic differentiation of BMSCs improved in the presence of Zn. 3-Zn-BG showed enhanced angiogenic potential, as confirmed by the tube formation assay. While Zn-doped BGs showed clearly superior biological properties in vitro, 3-Zn-BG and 0106-B1-BG equally promoted the formation of new bone in vivo; however, 3-Zn-BG reduced osteoclastic cells and vascular structures in vivo. The acquired data suggests that the differences regarding the in vivo and in vitro results may be due to modulation of inflammatory responses by Zn, as described in the literature. The inflammatory effect should be investigated further to promote clinical applications of Zn-doped BGs.
CRIS-Team Scopus Importer:2024-08-23

Biological impact of bioactive glasses and their dissolution products - Hoppe, Alexander; Boccaccini, Aldo R. (Biomaterials for Oral and Craniomaxillofacial Applications, 2015)
For many years, bioactive glasses (BGs) have been widely considered for bone tissue engineering applications due to their ability to bond to hard as well as soft tissue (a property termed bioactivity) and for their stimulating ef'fects on bone formation. Ionic dissolution products re'leased during the degradation of the BG matrix induce osteogenic gene expression leading to enhanced bone regeneration. Recently, adding bioactive metallic ions (e.g. boron, copper, cobalt, silver, zinc and strontium) to silicate (or phosphate and borate) glasses has emerged as a promising route for developing novel BG formulations with specific therapeutic functionalities, including anti'bacterial, angiogenic and osteogenic properties. The deg'radation behaviour of BGs can be tailored by adjusting the glass chemistry making these glass matrices potential car'rier systems for controlled therapeutic ion release. This book chapter summarises the fundamental aspects of the effect of ionic dissolution products from BGs on osteo'genesis and angiogenesis, whilst discussing novel BG compositions with controlled therapeutic ion release.

Biological Properties of Calcium Phosphate Bioactive Glass Composite Bone Substitutes: Current Experimental Evidence. - Karadjian, Maria; Essers, Christopher; Tsitlakidis, Stefanos; Reible, Bruno; Moghaddam, Arash; Boccaccini, Aldo R.; Westhauser, Fabian (International Journal of Molecular Sciences, 2019)
Standard treatment for bone defects is the biological reconstruction using autologous bone-a therapeutical approach that suffers from limitations such as the restricted amount of bone available for harvesting and the necessity for an additional intervention that is potentially followed by donor-site complications. Therefore, synthetic bone substitutes have been developed in order to reduce or even replace the usage of autologous bone as grafting material. This structured review focuses on the question whether calcium phosphates (CaPs) and bioactive glasses (BGs), both established bone substitute materials, show improved properties when combined in CaP/BG composites. It therefore summarizes the most recent experimental data in order to provide a better understanding of the biological properties in general and the osteogenic properties in particular of CaP/BG composite bone substitute materials. As a result, BGs seem to be beneficial for the osteogenic differentiation of precursor cell populations in-vitro when added to CaPs. Furthermore, the presence of BG supports integration of CaP/BG composites into bone in-vivo and enhances bone formation under certain circumstances.

Biological properties of chitosan/Eudragit E 100 and chitosan/poly(4-vinylpyridine) coatings electrophoretically deposited on AgNPs-decorated titanium substrate - Pawłowski, Łukasz; Akhtar, Muhammad Asim; Zieliński, Andrzej; Boccaccini, Aldo R. (Materials Letters, 2023)
The objective of the study was the determination of the response, in contact with human osteoblast-like MG-63 cells, of electrophoretically deposited coatings composed of chitosan (CS), Eudragit E 100 (EE100), or poly(4-vinylpyridine) (P4VP) on a silver nanoparticle (AgNPs)-decorated titanium substrate. Before deposition, the substrate was coated with silver by electro-reduction of silver nitrate. The coatings deposition was carried out in suspensions containing 0.1 % (w/w) of one of the biopolymers, EE100 or P4VP, with 0.1 % (w/w) of CS for 10 V and 1 min. Biopolymer coatings were successfully deposited while maintaining high uniformity. The deposited silver did not cause cytotoxicity. The biological study revealed that when compared to CS/P4VP, CS/EE100 coating performed better and showed a decrease in MG-63 cell viability only after three days of testing.
CRIS-Team Scopus Importer:2023-02-03
Keywords: Biological properties; Chitosan; Electrophoretic deposition; Eudragit; Poly(4-vinylpyridine); Silver nanoparticles

Biomaterials 2021: Future of biomaterials - Nanda, Himansu Sekhar; Thomas, Vinoy; Nukavarapu, Syam P.; Boccaccini, Aldo R. (Current Opinion in Biomedical Engineering, 2021)
CRIS-Team Scopus Importer:2021-06-25

Biomaterials at materials science and engineering (MSE) 2012 - Boccaccini, Aldo R.; Jandt, Klaus D. (Bioinspired, Biomimetic and Nanobiomaterials, 2013)

Biomaterials in cardiac tissue engineering: Ten years of research survey - Chen, Qi-Zhi; Harding, Sian E.; Ali, Nadire N.; Lyon, Alexander R.; Boccaccini, Aldo R. (Materials Science & Engineering R-Reports, 2008)
Driven by enormous clinical need, myocardial tissue engineering has become a prime focus of research within the field of tissue engineering. Myocardial tissue engineering combines isolated functional cardiomyocytes and a biodegradable or nondegradable biomaterial to repair diseased heart muscle. The challenges in heart muscle engineering include cell related issues (such as scale up in a short timeframe, efficiency of cell seeding or cell survival rate, and immune rejection), the design and fabrication of myocardial tissue engineering substrates, and the engineering of tissue constructs in vitro and in vivo. Several approaches have been put forward, and a number of models combining various polymeric biomaterials, cell sources and bioreactors have been developed in the last 10 years for myocardial tissue engineering. This review provides a comprehensive update on the biomaterials, as well as cells and biomimetic systems, used in the engineering of the cardiac muscle. The article is organized as follows. A historic perspective of the evolution of cardiac medicine and emergence of cardiac tissue engineering is presented in the first section. Following a review on the cells used in myocardial tissue engineering (second section), the third section presents a review on biomaterials used in myocardial tissue engineering. This section starts with an overview of the development of tissue engineering substrates and goes on to discuss the selection of biomaterials and design of solid and porous substrates. Then the applications of a variety of biomaterials used in different approaches of myocardial tissue engineering are reviewed in great detail, and related issues and topics that remain challenges for the future progress of the field are identified at the end of each subsection. This is followed by a brief review on the development of bioreactors (fourth section), which is an important achievement in the field of myocardial tissue engineering, and which is also related to the biomaterials developed. At the end of this article, the major achievements and remaining challenges are summarized, and the most promising paradigm for the future of heart muscle tissue engineering is proposed (fifth section). © 2007 Elsevier B.V. All rights reserved.
UnivIS-Import:2015-03-09:Pub.2008.tech.IW.LM.biomat
Keywords: Biomaterials; Bioreactors; Cardiac muscle; Cell therapy; Polymers; Tissue engineering

Biomaterial strategies to combat implant infections: new perspectives to old challenges - Braem, Annabel; Kamarudin, Nur Hidayatul Nazirah; Bhaskar, Nitu; Hadzhieva, Zoya; Mele, Andrea; Soulie, Jeremy; Linklater, Denver P.; Bonilla-Gameros, Linda; Boccaccini, Aldo R.; Roy, Ipsita; Drouet, Christophe; Ivanova, Elena P.; et al. (International Materials Reviews, 2023)
Peri-implant infection is rapidly becoming an - if not the most - important clinical challenge for indwelling medical devices. To alleviate the global rise in antibiotic use for the treatment of such infections, a plethora of biomaterials/bioengineering-based antimicrobial strategies are emerging to restrict or ideally to eliminate microbial adhesion and biofilm formation on implant surfaces. Yet, the development of such approaches faces specific challenges, like biocompatibility concerns, reduced antimicrobial effectiveness, long-term stability issues and antibiotic resistance development, which limit translation to the clinic. This review provides insights into the antimicrobial activity of current state-of-the-art biomaterial-based approaches to address the aforementioned issues. Translational research strategies and regulatory framework are also emphasised as key elements facilitating clinical implementation of anti-infective biomaterials. This review closes with the vision that the integration of computational tools and experimental databases using artificial intelligence (AI) would provide new insights for the accelerated development of next-generation biomaterial-based antimicrobial strategies.
CRIS-Team WoS Importer:2023-05-26

Biomedical Applications of Polyhydroxyalkanoates - Lizarraga-Valderrama, L. R.; Panchal, B.; Thomas, C.; Boccaccini, Aldo R.; Roy, I. (Wiley Blackwell, 2016)
Polyhydroxyalkanoates (PHAs) are a family of linear polyesters consisting of 3,4, 5 and 6-hydroxyacids, synthesized by a variety of bacterial species. PHAs are divided into two groups based on the number of carbon atoms in their monomer units; short-chain-length (scl) PHAs and medium-chain-length (mcl) PHAs. Biodegradability is an essential material property required for tissue engineering and drug delivery applications. Various methods of manufacture can be used to alter the biodegradability of PHA devices such as by blending with others polymers, increasing the porosity and increasing the exposed surface area. PHAs have also been demonstrated to be suitable for use as scaffolds in tissue engineering since they are easily degradable and favor proliferation and attachment of cells. In the field of skin tissue engineering research, various skin components, cytokines, growth factors, and transcription factors have been used experimentally. Melanocytes have been seeded on various polymer scaffolds, as well as sweat and sebaceous glands.
CRIS-Team Scopus Importer:2022-08-05
Keywords: Bacterial species; Biodegradability; Biomedical applications; Cytokines; Drug delivery applications; Linear polyesters; Polyhydroxyalkanoates; Sebaceous glands; Skin components; Tissue engineering

Biomedical applications of soy protein: A brief overview - Tansaz, Samira; Boccaccini, Aldo R. (Journal of Biomedical Materials Research Part A, 2016)
Soy protein (SP) based materials are gaining increasing interest for biomedical applications because of their tailorable biodegradability, abundance, being relatively inexpensive, exhibiting low immunogenicity, and for being structurally similar to components of the extracellular matrix (ECM) of tissues. Analysis of the available literature indicates that soy protein can be fabricated into different shapes, being relatively easy to be processed by solvent or melt based techniques. Furthermore soy protein can be blended with other synthetic and natural polymers and with inorganic materials to improve the mechanical properties and the bioactive behavior for several demands. This review discusses succinctly the biomedical applications of SP based materials focusing on processing methods, properties and applications highlighting future avenues for research.
Keywords: drug delivery systems; plant-derived protein; soy protein isolate; tissue engineering; wound dressing

Biomedical coatings on magnesium alloys - a review - Hornberger, Helga; Virtanen, Sannakaisa; Boccaccini, Aldo R. (Acta Biomaterialia, 2012)
This review comprehensively covers research carried out in the field of degradable coatings on Mg and Mg alloys for biomedical applications. Several coating methods are discussed, which can be divided, based on the specific processing techniques used, into conversion and deposition coatings. The literature review revealed that in most cases coatings increase the corrosion resistance of Mg and Mg alloys. The critical factors determining coating performance, such as corrosion rate, surface chemistry, adhesion and coating morphology, are identified and discussed. The analysis of the literature showed that many studies have focused on calcium phosphate coatings produced either using conversion or deposition methods which were developed for orthopaedic applications. However, the control of phases and the formation of cracks still appear unsatisfactory. More research and development is needed in the case of biodegradable organic based coatings to generate reproducible and relevant data. In addition to biocompatibility, the mechanical properties of the coatings are also relevant, and the development of appropriate methods to study the corrosion process in detail and in the long term remains an important area of research. © 2012 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
UnivIS-Import:2015-03-09:Pub.2012.tech.IW.LM.biomed
Keywords: Biodegradable materials; Coatings; Conversion; Deposition; Magnesium alloy

Biomimetic biohybrid nanofibers containing bovine serum albumin as a bioactive moiety for wound dressing - Homaeigohar, Shahin; Monavari, Mahshid; Koenen, Benedict; Boccaccini, Aldo R. (Materials Science and Engineering C, 2021)
For the first time, a biohybrid nanofibrous wound dressing is developed via green electrospinning of a blend solution of bovine serum albumin (BSA) (1 and 3 wt%) and polycaprolactone (PCL). In such a system, the components are miscible and interact through hydrogen bonding between the carbonyl group of PCL and the amine group of BSA, as verified by ATR-FTIR. As a result, the biohybrid nanofibers show a superior elastic modulus and elongation (300% and 58%, respectively) compared with the neat PCL nanofibers. The included protein induces a hydrophilicity effect to the PCL nanofibers, notably at the higher BSA content (3 wt%). In contrast to the neat nanofibers, the biohybrid ones are bioactive and encourage formation of biominerals (made of amorphous calcium carbonate) on the surface, after immersion in simulated body fluid (SBF). Based on the WST-8 cell viability tests, NIH3T3 fibroblast cells were seen to properly interact with the biohybrid mats and to proliferate in their proximity. SEM images show that the cells largely adhere onto such nanofibers even more than they do on the neat ones and adopt a flattened and stretched shape. In addition, the live/dead assay and phalloidin/DAPI staining assay confirm large cell viability and normal cell morphology on the biohybrid nanofiber mats after 4 days incubation. Taken together, BSA/PCL nanofibers are able to offer optimum mechanical properties (elasticity) as well as mineralization which can potentially stimulate the wound healing process, and can be considered a suitable candidate for wound dressing applications.
CRIS-Team Scopus Importer:2021-04-02
Keywords: Biohybrid; Electrospinning; Polycaprolactone; Protein; Wound dressing

Biomimetic calcium phosphate coatings for bioactivation of titanium implant surfaces: Methodological approach and in vitro evaluation of biocompatibility - Kreller, Thomas; Sahm, Franziska; Bader, Rainer; Boccaccini, Aldo R.; Jonitz-Heincke, Anika; Detsch, Rainer (Materials, 2021)
Ti6Al4V as a common implant material features good mechanical properties and corrosion resistance. However, untreated, it lacks bioactivity. In contrast, coatings with calcium phosphates (CaP) were shown to improve cell–material interactions in bone tissue engineering. Therefore, this work aimed to investigate how to tailor biomimetic CaP coatings on Ti6Al4V substrates using modified biomimetic calcium phosphate (BCP) coating solutions. Furthermore, the impact of substrate immersion in a 1 M alkaline CaCl2 solution (pH = 10) on subsequent CaP coating formation was examined. CaP coatings were characterized via scanning electron microscopy, x-ray diffraction, energy-dispersive x-ray spectroscopy, and laser-scanning microscope. Biocompatibility of coatings was carried out with primary human osteoblasts analyzing cell morphology, proliferation, collagen type 1, and interleukin 6 and 8 release. Results indicate a successful formation of low crystalline hydroxyapatite (HA) on top of every sample after immersion in each BCP coating solution after 14 days. Furthermore, HA coating promoted cell proliferation and reduced the concentration of interleukins compared to the uncoated surface, assuming increased biocompatibility.
CRIS-Team Scopus Importer:2021-07-16
Keywords: Hydroxyapatite; Interleukins; Primary human osteoblasts; Ti6Al4V

Biomimetic mineralized amorphous carbonated calcium phosphate-polycaprolactone bioadhesive composites as potential coatings on implant materials - Furko, Monika; Detsch, Rainer; Tolnai, István; Balázsi, Katalin; Boccaccini, Aldo R.; Balázsi, Csaba (Ceramics International, 2023)
Biomimetic mineralized (Mg, Zn, Sr) carbonated amorphous calcium phosphate (cACP) containing biodegradable polycaprolactone (PCL) coating was prepared via spin coating technology. The main role of PCL was to provide a controlled release of cACP for a prolonged period of time and to act as a bioadhesive, providing better adherence than that of pure cACP powder. The cACP and the cACP-PCL composite layers were optimized as very thin, non-continuous films on the surface of a commercial titanium alloy, maintaining its surface roughness. The powder layer and the composite film were morphologically, chemically, and biologically tested. In vitro biocompatibility measurements were performed using MC3T3-E1 cells. The cell viability significantly increased when cACP coatings and cACP-PCL composite were applied to the pure Ti6Al4V substrate. The pure PCL coating and the titanium substrate indicated similar biocompatibility, however, adding cACP powders into the polymer solution resulted in increased cell viability. LDH and ALP measurements showed a large number of living cells on the surface of all samples. The cell morphology study by Calcein/DAPI staining as well as SEM measurements demonstrated a well-adhered and spread, confluent cell monolayer. The long-term release of bioactive ions in SBF solution indicated that the biodegradability of composite coating is slightly faster than the cACP powder layer. All in vitro measurements confirmed the suitability of the developed composite layer as a potential bone substitute and bioactive coating on middle- and long-term implants.
CRIS-Team Scopus Importer:2023-03-24
Keywords: Amorphous calcium phosphate; Bioceramics; Biodegradability; Biopolymers; Composites

Biomimetic PGS based scaffolds for cardiac tissue engineering - Tallawi, Marwa (Friedrich-Alexander-Universität Erlangen-Nürnberg, 2015)

Biomimetic poly(glycerol sebacate) (PGS) membranes for cardiac patch application - Rai, Ranjana; Tallawi, Marwa; Barbani, Niccoletta; Frati, Caterina; Madeddu, Denise; Cavali, Stefano; Graiani, Gallia; Quaini, Frederico; Schubert, Dirk W.; Roether, Judith; Rosellini, Elisabetta; Boccaccini, Aldo R. (Materials Science and Engineering C, 2013)
In this study biomimetic poly(glycerol sebacate) PGS matrix was developed for cardiac patch application. The rationale was that such matrices would provide conducive environment for the seeded cells at the interphase with PGS. From the microstructural standpoint, PGS was fabricated into dense films and porous PGS scaffolds. From the biological aspect, biomimetic PGS membranes were developed via covalently binding peptides Tyr-Ile-Gly-Ser-Arg (YIGSR) and Gly-Arg-Gly-Asp-Ser-Pro (GRGDSP), corresponding to the epitope sequences of laminin and fibronectin, respectively onto the surface. To improve and enhance homogenous binding of peptides onto the PGS surface, chemical modification of its surface was carried out. A sequential regime of alkaline hydrolysis with 0.01 M NaOH for 5 min and acidification with 0.01 M HCl for 25 s was optimal. More COOH chemical group was exposed without causing deleterious effect on the bulk properties of the polymer as revealed by the physicochemical analysis carried out. HPLC analysis, chemical imaging and ToF-SIMS were able to establish the successful homogenous functionalization of PGS membranes with the peptides. Finally, the developed biomimetic membranes supported the adhesion and growth of rat and human cardiac progenitor cells.
UnivIS-Import:2015-03-09:Pub.2013.tech.IW.LM.biomim
Keywords: Poly(glycerol sebacate); Cardiac patch; Biomimetic; Surface modification; Laminin; Fibronectin

Biomineralization inspired 3D printed bioactive glass nanocomposite scaffolds orchestrate diabetic bone regeneration by remodeling micromilieu - Xu, Zeqian; Qi, Xuanyu; Bao, Minyue; Zhou, Tian; Shi, Junfeng; Xu, Zhiyan; Zhou, Mingliang; Boccaccini, Aldo R.; Zheng, Kai; Jiang, Xinquan (Bioactive Materials, 2023)
Type II diabetes mellitus (TIIDM) remains a challenging clinical issue for both dentists and orthopedists. By virtue of persistent hyperglycemia and altered host metabolism, the pathologic diabetic micromilieu with chronic inflammation, advanced glycation end products accumulation, and attenuated biomineralization severely impairs bone regeneration efficiency. Aiming to “remodel” the pathologic diabetic micromilieu, we 3D-printed bioscaffolds composed of Sr-containing mesoporous bioactive glass nanoparticles (Sr-MBGNs) and gelatin methacrylate (GelMA). Sr-MBGNs act as a biomineralization precursor embedded in the GelMA-simulated extracellular matrix and release Sr, Ca, and Si ions enhancing osteogenic, angiogenic, and immunomodulatory properties. In addition to angiogenic and anti-inflammatory outcomes, this innovative design reveals that the nanocomposites can modulate extracellular matrix reconstruction and simulate biomineralization by activating lysyl oxidase to form healthy enzymatic crosslinked collagen, promoting cell focal adhesion, modulating osteoblast differentiation, and boosting the release of OCN, the noncollagenous proteins (intrafibrillar mineralization dependent), and thus orchestrating osteogenesis through the Kindlin-2/PTH1R/OCN axis. This 3D-printed bioscaffold provides a multifunctional biomineralization-inspired system that remodels the “barren” diabetic microenvironment and sheds light on the new bone regeneration approaches for TIIDM.
CRIS-Team Scopus Importer:2023-02-24
Keywords: 3D printing; Biomineralization; Enzymatic cross-links; Sr-containing mesoporous bioactive glass nanoparticles; Type II Diabetes mellitus

Biomolecule and Ion Releasing Mesoporous Nanoparticles: Nonconvergent Osteogenic and Osteo-immunogenic Performance - Khodaei, Azin; Nawaz, Qaisar; Zhu, Zhengqing; Amin Yavari, Saber; Weinans, Harrie; Boccaccini, Aldo R. (ACS Applied Materials and Interfaces, 2024)
Immune-involved cell communications have recently been introduced as key role players in the fate of mesenchymal stem cells in making bone tissue. In this study, a drug delivery system for bone (re)generation based on copper-doped mesoporous bioactive glass nanoparticles (BGNPs) was developed to codeliver copper as a biologically active ion and icariin as an anti-inflammatory agent. This design was based on temporal inflammation fluctuations from proinflammatory to anti-inflammatory during bone generation. Three in vitro models were performed with human mesenchymal stem cells (hMSCs) to verify the osteo-immunomodulatory effects of released copper ions and icariin: nonstimulated, co-conditioned with macrophage medium and co-cultured with macrophages. Both icariin and copper showed increased levels of alkaline phosphatase activation, indicating a direct osteogenic effect. Copper-doped BGNPs showed the highest increase of osteo-immunogenic properties in a mineralization assay and also induced short-term inflammation. However, the mineralization dropped in copper doped BGNPs after loading with icariin due to copper-icariin chelate formation and inhibition of the early inflammatory phase in the immune-stimulated in vitro models. In the absence of copper, the direct osteogenic properties of icariin overtook its osteo-immunogenic inhibition and increased calcification. Overall, BGNPs doped with 5 mol % copper and no icariin showed the highest bone-forming capacity.
CRIS-Team Scopus Importer:2024-12-06
Keywords: Bone regeneration; Flavonoid; Immunomodulatory; Inflammation; Tissue engineering

Bioplotting of a bioactive alginate dialdehyde-gelatin composite hydrogel containing bioactive glass nanoparticles - Leite, Alvaro J.; Sarker, Bapi; Zehnder, Tobias; Silva, Raquel; Mano, Joao F.; Boccaccini, Aldo R. (Biofabrication, 2016)
Keywords: alginate; bioactive glass nanoparticles; bioactivity; biofabrication; bioplotting; composite; gelatin

Bioprinted 3D calcium phosphate scaffolds with gentamicin releasing capability - Meissner, Ruth; Bertol, Liciane; Ur Rehman, Muhammad Atiq; Loureiro Dos Santos, Luis Alberto; Boccaccini, Aldo R. (Ceramics International, 2019)
We investigated the suitability of 3D printed calcium phosphate scaffolds as drug carriers. The 3D powder printing process utilized a-tricalcium phosphate (alpha-TCP) as a solid phase and deionized water with 2.5% disodium hydrogen phosphate as a setting accelerator. The antibiotic gentamicin sulfate was incorporated by mixing it into alpha-TCP powder before printing. Two different concentrations of gentamicin (3 wt%, 7 wt%) were used to study the correlation between drug release kinetics and gentamicin content in the scaffolds. The scaffolds were hardened at 100% humidity. The synthesized scaffolds were characterized in terms of morphology, composition, mechanical strength, in vitro bioactivity and drug release kinetics. X-ray diffraction (XRD) analysis revealed that the alpha-TCP converted into calcium deficient hydroxyapatite (CDHA) during the printing process. Scanning electron microscopy (SEM) showed the typical needle-like structure of CDHA. Gentamicin release was investigated for a period of two weeks with an initial burst release. The produced scaffolds formed calcium enriched apatite crystals on their surface after three days of incubation in simulated body fluid.
CRIS-Team WoS Importer:2019-03-22

Bioprinting with bioactive alginate dialdehyde-gelatin (ADA-GEL) composite bioinks: Time-dependent in-situ crosslinking via addition of calcium-silicate particles tunes in vitro stability of 3D bioprinted constructs - Heid, Susanne; Becker, Kevin; Byun, Jiwon; Biermann, Isabell; Neščáková, Zuzana; Zhu, Hui; Groll, Jürgen; Boccaccini, Aldo R. (Bioprinting, 2022)
The development of hydrogels suitable for biofabrication is essential to enable advanced approaches for tissue engineering and regenerative medicine. Applications in both hard and soft tissues require tailor-made bioinks to guide cellular behavior in a 3D matrix. In this study we aimed to enhance the stability and adjust the degradation behavior of alginate dialdehyde-gelatine (ADA-GEL) hydrogels using an in-situ crosslinking mechanism additionally to external crosslinking. To test this approach, we added 0.1 and 0.5% (w/v) bioactive inorganic fillers (BIF) based on sub-micrometric calcium-silicate particles to ADA-GEL hydrogels. Such BIF release bivalent Ca2+ ions which can internally crosslink alginate chains and tune the degradation of the hydrogel over 28 days of incubation. It was found that pure ADA-GEL dissolved quickly after the first day while the composite hydrogels remained stable exhibiting reduced degradation (20–50% of the initial weight). 3D (bio)printing of composite bioinks revealed improved printing accuracy, 3D shape fidelity as well as cell spreading throughout the entire matrix during 14 days of evaluation. Chemically, BIF did not seem to have an influence on ADA-GEL Schiff's base bonds and also the mechanical properties of the composite hydrogels were comparable to those of pure ADA-GEL with Young's moduli of about 4 kPa. Comprehensive rheology measurements were carried out to determine printing parameters and the influence of BIF on the bioprinting process. We conclude that the novel hydrogel composition based on ADA-GEL system incorporating calcium-silicate BIF exhibits tunable behavior in vitro up to at least 28 days of incubation leading to improved stability and time-dependent cell behavior in 3D bioprinted constructs.
CRIS-Team Scopus Importer:2022-06-10
Keywords: Alginate dialdehyde; Bioactive glass; Bioprinting; Composite bioink; Fibroblasts; Gelatin; Soft tissue engineering

Bioreactors in Regenerative Medicine - From a Technical Device to a Reconstructive Alternative? - Polykandriotis, E.; Schmidt, V. J.; Kneser, U.; Jianming, S.; Boccaccini, Aldo R.; Horch, Raymund E. (Handchirurgie, Mikrochirurgie, Plastische Chirurgie, 2012)
With the advent of the era of tissue engineering (TE), experimental settings have been developed that allow for a defined environment with optimised cell growth conditions and/or the production of specific substitutes. These isolated systems have been termed "bioreactors". By translating the principles of bioreactors into an in vivo context, advances in biomaterial sciences and cell biology have been merged into an integrative research concept. Even today, in the age of regenerative Medicine (RegMed) the transfer of experimental in vitro findings into a clinical in vivo approach still remains a vast challenge. In order to fulfil these specific requirements bioreactors had to be defined anew. Latest advances in areas like reconstructive medicine (the arteriovenous loop as a means of organogenesis) or modern wound management (topical negative pressure therapy as a perfusion bioreactor) give new impulses towards the translation of RegMed concepts into the clinical routine.
Keywords: angiogenesis; tissue engineering; growth factors; experimental transplantation; bioreactors; negative pressure therapy

Bio-response of copper-magnesium co-substituted mesoporous bioactive glass for bone tissue regeneration - Anand, Akrity; Kaňková, Hana; Hájovská, Zuzana; Galusek, Dušan; Boccaccini, Aldo R.; Galusková, Dagmar (Journal of Materials Chemistry B, 2024)
Mesoporous bioactive glass (MBG) is widely acknowledged in bone tissue engineering due to its mesoporous structure, large surface area, and bioactivity. Recent research indicates that introduction of metallic ions has beneficial impacts on bone metabolism and angiogenesis. Thus, the features of MBG can be modified by incorporating combinations of ions, such as magnesium (Mg) and copper (Cu), which can play a considerable role in bone formation, influencing angiogenesis, osteogenesis, as well as antibacterial properties. In this study, Mg and Cu were co-doped for the first time (in a ratio of 1 : 1) in 80SiO2-5P2O5-(15 − 2x)CaO-xMgO-xCuO glass composition with x = 0, 0.5, 1, and 2 mol%, synthesized using the sol-gel and evaporation-induced self-assembly method. X-ray diffraction analysis confirmed the amorphous nature of the powders, while inductively coupled plasma-optical emission spectrometry verified the existence of dopant ions in the respective amounts. The nitrogen sorption method indicated the formation of uniform cylindrical mesopores which are open at both ends and a high surface area of the powders. TEM images show fringes, indicating an ordered mesoporous structure in all MgCu co-doped systems. In vitro bioactivity was observed in all MBG powders, confirmed by the formation of an apatite phase when placed in simulated body fluid (SBF). Flake-like microstructure characteristics of HAp crystals found on the surface of MBG powders were visualized using FESEM. Cytotoxicity tests at lower concentrations (0.1 and 1 wt/vol%) of co-doped 2MC MBG (co-doping up to 2 mol%) showed cell proliferation and viability of osteoblast-like MG-63 cells and normal human dermal fibroblast (NHDF) cells similar to the basic glass 80S. Antibacterial study of MBG pellets showed an increment in the zone of inhibition with the sequential addition of doping ions. The turbidity measurement of bacterial cultures revealed that the optimal concentration for effectively inhibiting bacterial growth was 1 wt/vol% (i.e., 10 mg mL−1) concentration of MBG extracts. The result suggested that the incorporation of Mg and Cu ions in MBG in lower concentrations of up to 2 mol% can be useful in bone regeneration owing to bioactivity, cell proliferation, and antibacterial characteristics.
CRIS-Team Scopus Importer:2024-02-16

Biosilicate®–gelatine bone scaffolds by the foam replica technique: development and characterization - Desimone, Deborah; Li, Wei; Roether, Judith; Schubert, Dirk W.; Crovace, Murilo; Rodrigues, Ana; Zanotto, Edgar; Boccaccini, Aldo R. (Science and Technology of Advanced Materials, 2013)
The development of bioactive glass-ceramic materials has been a topic of great interest aiming at enhancing the mechanical strength of traditional bioactive scaffolds. In the present study, we test and demonstrate the use of Biosilicate® glass-ceramic powder to fabricate bone scaffolds by the foam replica method. Scaffolds possessing the main requirements for use in bone tissue engineering (95% porosity, 200–500 μm pore size) were successfully produced. Gelatine coating was investigated as a simple approach to increase the mechanical competence of the scaffolds. The gelatine coating did not affect the interconnectivity of the pores and did not significantly affect the bioactivity of the Biosilicate® scaffold. The gelatine coating significantly improved the compressive strength (i.e. 0.80 ± 0.05 MPa of coated versus 0.06 ± 0.01 MPa of uncoated scaffolds) of the Biosilicate® scaffold. The combination of Biosilicate® glass-ceramic and gelatine is attractive for producing novel scaffolds for bone tissue engineering.
UnivIS-Import:2015-03-09:Pub.2013.tech.IW.LM.biosil
Keywords: bioactivity; bone tissue engineering; glass-ceramics; scaffolds

Biosilicate®-gelatine bone scaffolds by the foam replica technique: Development and characterization - Desimone e Silva, Deborah; Li, Wei; Roether, Judith; Schubert, Dirk W.; Crovace, Murilo; Rodrigues, Ana; Zanotto, Edgar; Boccaccini, Aldo R. (Science and Technology of Advanced Materials, 2013)
The development of bioactive glass-ceramic materials has been a topic of great interest aiming at enhancing the mechanical strength of traditional bioactive scaffolds. In the present study, we test and demonstrate the use of Biosilicate® glass-ceramic powder to fabricate bone scaffolds by the foam replica method. Scaffolds possessing the main requirements for use in bone tissue engineering (95% porosity, 200–500 μm pore size) were successfully produced. Gelatine coating was investigated as a simple approach to increase the mechanical competence of the scaffolds. The gelatine coating did not affect the interconnectivity of the pores and did not significantly affect the bioactivity of the Biosilicate® scaffold. The gelatine coating significantly improved the compressive strength (i.e. 0.80 ± 0.05 MPa of coated versus 0.06 ± 0.01 MPa of uncoated scaffolds) of the Biosilicate® scaffold. The combination of Biosilicate® glass-ceramic and gelatine is attractive for producing novel scaffolds for bone tissue engineerin
Keywords: bioactivity; glass-ceramics; bone tissue engineering; scaffolds

Biosynthesis of Zinc Oxide Nanoparticles on l-Carnosine Biofunctionalized Polyacrylonitrile Nanofibers; a Biomimetic Wound Healing Material - Homaeigohar, Shahin; Assad, Mhd Adel; Azari, Amir Hossein; Ghorbani, Farnaz; Rodgers, Chloe; Dalby, Matthew J.; Zheng, Kai; Xu, Rongyao; Elbahri, Mady; Boccaccini, Aldo R. (ACS Applied Bio Materials, 2023)
Multifunctional biohybrid nanofibers (NFs) that can simultaneously drive various cellular activities and confer antibacterial properties are considered desirable in producing advanced wound healing materials. In this study, a bionanohybrid formulation was processed as a NF wound dressing to stimulate the adhesion and proliferation of fibroblast and endothelial cells that play a major role in wound healing. Polyacrylonitrile (PAN) electrospun NFs were hydrolyzed using NaOH and biofunctionalized with l-carnosine (CAR), a dipeptide which could later biosynthesize zinc oxide (ZnO) nanoparticles (NPs) on the NFs surface. The morphological study verified that ZnO NPs are uniformly distributed on the surface of CAR/PAN NFs. Through EDX and XRD analysis, it was validated that the NPs are composed of ZnO and/or ZnO/Zn(OH)2. The presence of CAR and ZnO NPs brought about a superhydrophilicity effect and notably raised the elastic modulus and tensile strength of Zn-CAR/PAN NFs. While CAR ligands were shown to improve the viability of fibroblast (L929) and endothelial (HUVEC) cells, ZnO NPs lowered the positive impact of CAR, most likely due to their repulsive negative surface charge. A scratch assay verified that CAR/PAN NFs and Zn-CAR/PAN NFs aided HUVEC migration more than PAN NFs. Also, an antibacterial assay implied that CAR/PAN NFs and Zn-CAR/PAN NFs are significantly more effective in inhibiting Staphylococcus aureus (S. aureus) than neat PAN NFs are (1000 and 500%, respectively). Taken together, compared to the neat PAN NFs, CAR/PAN NFs with and without the biosynthesized ZnO NPs can support the cellular activities of relevance for wound healing and inactivate bacteria.
CRIS-Team Scopus Importer:2023-11-03
Keywords: biofunctionalization; nanofiber; polyacrylonitrile; wound healing; zinc oxide

Bio-templated bioactive glass particles with hierarchical macro-nano porous structure and drug delivery capability - Zheng, Kai; Bortuzzo, Judith Agnes; Liu, Yufang; Li, Wei; Pischetsrieder, Monika; Roether, Judith; Lu, Miao; Boccaccini, Aldo R. (Colloids and Surfaces B: Biointerfaces, 2014)
Hierarchically porous bioactive glass particles (BGPs) were synthesized by a facile sol-gel process using pollen grains as the templates. The synthesized pollen-templated bioactive glass particles (PBGPs) exhibited dual macro-nano porous structure. The macro pores ( 1μm) were inherited from the template of pollen grains while the nano pores ( 9.5nm) were induced by the intrinsic mechanism of the sol-gel process. PBGPs possessed a high specific surface area (111.4m/g) and pore volume (0.35cm/g). Hydroxyapatite (HA) formation on PBGPs was detected within 3 days after immersion in simulated body fluid (SBF). Due to their larger specific surface area and pore volume, PBGPs could be loaded with more tetracycline hydrochloride (TCH) than non-templated BGPs and conventional melt-derived 45S5 BGPs. In addition, PBGPs exhibited a low initial burst release (within 10% of the loaded amount) within 18h and a sustained release with a two-stage release pattern for up to 6 days in phosphate buffered saline (PBS). The antibacterial assay confirmed that the TCH-loaded PBGPs could release TCH within 5 days, and the released TCH could reach the minimum inhibitory concentration (MIC) against Escherichia coli. MTT assay indicated that PBGPs showed non-cytotoxic effects toward human hepatocellular carcinoma (Hep G2) cells after co-culture for up to 72h in vitro. These results showed that the biocompatible hierarchically macro-nano porous PBGPs are potential for bone regeneration and local drug delivery applications.
Keywords: Bio-template; Bioactive glass; Drug delivery; Hierarchical pores

Bisphosphonate-based strategies for bone tissue engineering and orthopedic implants - Pablo Cattalini, Juan; Boccaccini, Aldo R.; Lucangioli, Silvia; Mourino, Viviana (Tissue Engineering - Part B: Reviews, 2013)
UnivIS-Import:2015-03-09:Pub.2013.tech.IW.LM.bispho

Bone formation and degradation of a highly porous biphasic calcium phosphate ceramic in presence of BMP-7, VEGF and mesenchymal stem cells in an ectopic mouse model - Detsch, Rainer; et al. (Journal of Cranio-Maxillofacial Surgery, 2010)
Introduction: Angiogenesis and mesenchymal stem cells (MSCs) promote osteogenesis. The aim of the present study was to evaluate whether bone morphogenetic protein (BMP-7) promoted osteoinduction could be enhanced by combining it with vascular endothelial growth factor (VEGF) or MSCs in highly porous biphasic calcium phosphate (BCP) ceramics. Materials and methods: BCP ceramic blocks were implanted in an ectopic site in 24 mice (BMP-7 vs. BMP-7/VEGF; BMP-7 vs. BMP-7/MSCs and BMP-7 vs. Control; each group n = 8). Specimens were analysed 12 weeks after surgery by environmental scanning electron microscopy (ESEM) and Giemsa staining. Results: In all implanted scaffolds, newly formed bone was observed, even in the control site. No statistical differences in the amount of new bone were found in the presence of BMP-7 compared to BMP-7/VEGF (p = 1.0) or BMP-7/MSCs (p = 0.786). ESEM revealed a degradation of the scaffolds. A higher degradation was observed in areas where no bone-implant contact was present compared to areas where the ceramic was integrated in newly formed bone. Conclusions: Neither VEGF nor MSCs enhanced BMP-7 induced bone formation under the selected conditions. The present ceramic seemed to be osteoinductive and degradable, making this material suitable for bone tissue engineering. © 2010 European Association for Cranio-Maxillo-Facial Surgery.
Keywords: BMP-7; calcium phosphate ceramic; ectopic bone formation; growth factors; mesenchymal stem cells; VEGF

Bone tissue engineering by using a combination of polymer/Bioglass composites with human adipose-derived stem cells - Lu, Wei; Ji, Kun; Kirkham, Jennifer; Yan, Yu; Boccaccini, Aldo R.; Kellett, Margaret; Jin, Yan; Yang, Xuebin B. (Cell and Tissue Research, 2014)
Translational research in bone tissue engineering is essential for "bench to bedside" patient benefit. However, the ideal combination of stem cells and biomaterial scaffolds for bone repair/regeneration is still unclear. The aim of this study is to investigate the osteogenic capacity of a combination of poly(DL-lactic acid) (PDLLA) porous foams containing 5 wt% and 40 wt% of Bioglass particles with human adipose-derived stem cells (ADSCs) in vitro and in vivo. Live/dead fluorescent markers, confocal microscopy and scanning electron microscopy showed that PDLLA/Bioglass porous scaffolds supported ADSC attachment, growth and osteogenic differentiation, as confirmed by enhanced alkaline phosphatase (ALP) activity. Higher Bioglass content of the PDLLA foams increased ALP activity compared with the PDLLA only group. Extracellular matrix deposition after 8 weeks in the in vitro cultures was evident by Alcian blue/Sirius red staining. In vivo bone formation was assessed by using scaffold/ADSC constructs in diffusion chambers transplanted intraperitoneally into nude mice and recovered after 8 weeks. Histological and immunohistochemical assays indicated significant new bone formation in the 40 wt% and 5 wt% Bioglass constructs compared with the PDLLA only group. Thus, the combination of a well-developed biodegradable bioactive porous PDLLA/Bioglass composite scaffold with a high-potential stem cell source (human ADSCs) could be a promising approach for bone regeneration in a clinical setting. © 2014 Springer-Verlag Berlin Heidelberg.
Keywords: Adipose-derived stem cells; Biodegradable polymers; Bone tissue engineering; In vivo; PDLLA/Bioglass® composite

Bone tissue engineering therapeutics: controlled drug delivery in three-dimensional scaffolds - Mourino, Viviana; Boccaccini, Aldo R. (Journal of the Royal Society Interface, 2010)
This paper provides an extensive overview of published studies on the development and applications of three-dimensional bone tissue engineering (TE) scaffolds with potential capability for the controlled delivery of therapeutic drugs. Typical drugs considered include gentamicin and other antibiotics generally used to combat osteomyelitis, as well as anti-inflammatory drugs and bisphosphonates, but delivery of growth factors is not covered in this review. In each case reviewed, special attention has been given to the technology used for controlling the release of the loaded drugs. The possibility of designing multifunctional three-dimensional bone TE scaffolds for the emerging field of bone TE therapeutics is discussed. A detailed summary of drugs included in three-dimensional scaffolds and the several approaches developed to combine bioceramics with various polymeric biomaterials in composites for drug-delivery systems is included. The main results presented in the literature are discussed and the remaining challenges in the field are summarized with suggestions for future research directions. © 2009 The Royal Society.
UnivIS-Import:2015-03-09:Pub.2010.tech.IW.LM.boneti
Keywords: Bioactive glass; Biodegradable materials; Bone tissue engineering; Drug release; Drug-delivery system; Scaffolds

Bone tissue scaffolds based on antimicrobial SiO2-Na2O-Al2O3-CaO-B2O3 glass - Esteban-Tejeda, Leticia; Zheng, Kai; Prado, Catuxa; Cabal, Belen; Torrecillas, Ramon; Boccaccini, Aldo R.; Moya, Jose S. (Journal of Non-Crystalline Solids, 2016)
This paper reports the fabrication, microstructural characterization, mechanical properties and antimicrobial activity of scaffolds obtained from a soda-lime glass powder constituted by micro-spheres belonging to the SiO-NaO-AlO-CaO - BO system. Scaffolds with a porosity > 90% were fabricated using the foam replication method in the temperature range of 750-850 °C. The highest compressive strength value (0.2 MPa) was obtained for the scaffolds sintered at 850 °C. The observed mechanical properties were rationalized considering the scaffold singular microstructure of the struts constituted by a dense packing of microspheres ranging from 4 to 30 μm interlocked by nepheline needle-like crystals. The antimicrobial test was performed against three different microorganisms: Escherichia coli, Staphylococcus aureus and Candida krusei (yeast). A 45S5 Bioglass® scaffold was also tested for comparison. A window glass scaffold was used as control. In all cases a safe disinfection was obtained (reduction > 99.9% = log of reduction > 3). The antimicrobial activity was found to be similar to that of 45S5 Bioglass® based scaffolds. However, the soda-lime scaffold sintered at 850 °C exhibited a higher antimicrobial activity (log of reduction > 5 = reduction > 99.999%) against C. krusei, which is a microorganism resistant to multiples biocides, than the Bioglass® scaffold (log of reduction < 2 = reduction > 99.0%).
Keywords: Antimicrobial; Scaffold; Soda-lime glass-ceramics

Borate and silicate bioactive glass coatings prepared by nanosecond pulsed laser deposition - Rau, Julietta V.; De Bonis, Angela; Curcio, Mariangela; Schuhladen, Katharina; Barbaro, Katia; De Bellis, Giovanni; Teghil, Roberto; Boccaccini, Aldo R. (Coatings, 2020)
Silicate (13-93) and borate (13-93-B3) bioactive glass coatings were successfully deposited on titanium using the nanosecond Pulsed Laser Deposition technique. The coatings’ microstructural characteristics, compositions and morphologies were examined by a number of physico-chemical techniques. The deposited coatings retain the same functional groups of the targets, are a few microns thick, amorphous, compact and crack free. Their surface is characterized by the presence of micrometric and nanometric particles. The surface topography, investigated by Atomic Force Microscopy, is characterized by spherical or ellipsoidal particles of the 0.2–3 µm size range for the 13-93 silicate bioactive glass film and of the 0.1–1 µm range for the 13-93-B3 borate bioactive glass coating. Equine adipose tissue-derived mesenchymal stem cells (ADMSCs) were applied for biological tests and the osteogenic differentiation activity of cells on the deposited coatings was studied after ADMSCs growth in osteogenic medium and staining with Alizarin Red. Cytocompatibility and osteogenic differentiation tests have shown that thin films retain the biocompatibility properties of the target silicate and borate glass, respectively. On the other hand, no antibacterial activity of the borate glass films was observed, suggesting that ion doping is advisable to inhibit bacterial growth on the surface of borate glass thin films.
CRIS-Team Scopus Importer:2020-11-27
Keywords: Antibacterial activity; Borate bioactive glass coatings; Cytocompatibility; Equine adipose tissue-derived stem cells; Nanosecond pulsed laser deposition; Silicate bioactive glass coatings

Borate Bioactive Glasses (BBG): Bone Regeneration, Wound Healing Applications, and Future Directions - Ege, Duygu; Zheng, Kai; Boccaccini, Aldo R. (ACS Applied Bio Materials, 2022)
Since the early 2000s, borate bioactive glasses (BBGs) have been extensively investigated for biomedical applications. The research so far indicates that BBGs frequently exhibit superior bioactivity and bone healing capacity compared to silicate glasses. They are also suitable candidates as drug delivery devices for infection or disease treatment such as osteoporosis. Additionally, BBGs are also an excellent option for wound healing applications, which includes the availability of commercial (FDA approved) microfibrous BBG dressings to treat chronic wounds. By addition of modifying ions, the bone or wound healing capacity of BBGs can be enhanced. For instance, addition of copper ions into BBGs was shown to drastically increase blood vessel formation for wound healing applications. Moreover, addition of ions such as magnesium, strontium, and cobalt improves bone healing. Other recent research interest related to BBGs is focused on nerve and muscle regeneration applications, while cartilage regeneration is also suggested as a potential application field for BBGs. BBGs are commonly produced by melt-quenching; however, sol-gel processing of BBGs is emerging and appears to be a promising alternative. In this review paper, the physical and biological characteristics of BBGs are analyzed based on the available literature, the applications of BBGs are discussed, and future research directions are suggested.
CRIS-Team WoS Importer:2022-08-05

Boric acid and Molybdenum trioxide synergistically stimulate osteogenic differentiation of human bone marrow-derived mesenchymal stromal cells - Scheurle, A.; Kunisch, E.; Boccaccini, Aldo R.; Walker, T.; Renkawitz, T.; Westhauser, F. (Journal of Trace Elements in Medicine and Biology, 2024)
Introduction: Metals and their metal ions have been shown to exhibit certain biological functions that make them attractive for use in biomaterials, for example in bone tissue engineering (BTE) applications. Recent data shows that Molybdenum (Mo) is a potent inducer of osteogenic differentiation in human bone marrow-derived mesenchymal stromal cells (BMSCs). On the other hand, while boron (B) has been shown to enhance vascularization in BTE applications, its impact on osteogenic differentiation is volatile: while improved osteogenic differentiation has been described, other data show that B might slow down osteogenic differentiation or reduce the calcification of the extracellular matrix (ECM) when applied in higher doses. Still, the combination of pro-osteogenic Mo and pro-angiogenic B is certainly attractive in the context of biomaterials intended for the use in BTE. Methods: Therefore, the combined effect of molybdenum trioxide and boric acid at different ratios was investigated in this study to evaluate the effects on the viability, proliferation, osteogenic differentiation, ECM production and maturation of BMSCs. Results: Mo ions proved to be stronger osteoinductive compared to B, in fact, while some osteogenic differentiation markers were downregulated in the presence of B, the presence of Mo provided compensation. The combined application of B and Mo indicated a combination of individual effects, partially even enhancing the expected combined performance of the single stimulations. Conclusions: The combination of B and Mo might be beneficial for BTE applications since the limited osteogenic properties of B can be compensated by Mo. Furthermore, since B is known to be pro-angiogenic, the combination of both substances may synergistically lead to improved vascularization and bone regeneration. Future studies should assess the angiogenic performance of this combination in greater detail.
CRIS-Team Scopus Importer:2024-02-16
Keywords: Boron; Cell viability; Extracellular matrix formation; Human bone marrow-derived mesenchymal stromal cells; Molybdenum; Osteogenic differentiation; Trace elements

Boron-containing bioactive glasses in bone and soft tissue engineering - Balasubramanian, Preethi; Büttner, Teresa; Miguez Pacheco, Valentina; Boccaccini, Aldo R. (Journal of the European Ceramic Society, 2018)
Keywords: Angiogenesis; Bioactive glasses; Bioactivity; Borate; Borosilicate; In vivo; Osteogenesis

Borosilicate glass foams from glass packaging residues - Chinnam, Rama Krishna Satish; Molinaro, Silvia; Bernardo, Enrico; Boccaccini, Aldo R. (Ceramics for Environmental and Energy Applications II, 2014)
In the present study, pharmaceutical waste derived borosilicate glass (BSG) was investigated to fabricate foams without the addition of external foaming agents. Foaming was shown to occur when glass powder compacts were sintered at 950°C and above. It was found that foaming ability depended on the initial powder particle size and it was higher when the glass particle size was <38µm, while samples with a particle size of <100µm and <250µm exhibited bulk nature (no foaming). The exact reasons for the self-foaming behavior of BSG waste were not determined; however a hypothesis was proposed to explain the foaming mechanism. The novel borosilicate glass foams developed here are of interest for acoustic and thermal insulation structures exhibiting high thermal shock resistance.
CRIS-Team Scopus Importer:2022-08-05
Keywords: Borosilicate glass; Foaming agents; Freeze tolerance; Thermal insulation; Thermal shock resistance

Boswellia sacra Extract-Loaded Mesoporous Bioactive Glass Nano Particles: Synthesis and Biological Effects - Ilyas, Kanwal; Singer, Lamia; Akhtar, Muhammad Asim; Bourauel, Christoph P.; Boccaccini, Aldo R. (Pharmaceutics, 2022)
Bioactive glasses (BGs) are being increasingly considered for numerous biomedical applications. The loading of natural compounds onto BGs to increase the BG biological activity is receiving increasing attention. However, achieving efficient loading of phytotherapeutic compounds onto the surface of bioactive glass is challenging. The present work aimed to prepare novel amino-functionalized mesoporous bioactive glass nanoparticles (MBGNs) loaded with the phytotherapeutic agent Boswellia sacra extract. The prepared amino-functionalized MBGNs showed suitable loading capacity and releasing time. MBGNs (nominal composition: 58 wt% SiO2, 37 wt% CaO, 5 wt% P2O5) were prepared by sol-gel-modified co-precipitation method and were successfully surface-modified by using 3-aminopropyltriethoxysilane (APTES). In order to evaluate MBGNs loaded with Boswellia sacra, morphological analysis, biological studies, physico-chemical and release studies were performed. The successful functionalization and loading of the natural compound were confirmed with FTIR, zeta-potential measurements and UV-Vis spectroscopy, respectively. Structural and morphological evaluation of MBGNs was done by XRD, SEM and BET analyses, whereas the chemical analysis of the plant extract was done using GC/MS technique. The functionalized MBGNs showed high loading capacity as compared to non-functionalized MBGNs. The release studies revealed that Boswellia sacra molecules were released via controlled diffusion and led to antibacterial effects against S. aureus (Gram-positive) bacteria. Results of cell culture studies using human osteoblastic-like cells (MG-63) indicated better cell viability of the Boswellia sacra-loaded MBGNs as compared to the unloaded MBGNs. Therefore, the strategy of combining the properties of MBGNs with the therapeutic effects of Boswellia sacra represents a novel, convenient step towards the development of phytotherapeutic-loaded antibacterial, inorganic materials to improve tissue healing and regeneration.
CRIS-Team Scopus Importer:2022-01-28
Keywords: Antibacterial; Bioactive glass; Boswellia sacra; Functionalization; Phytotherapeutics

Bottom-Up Assembly of Silica and Bioactive Glass Supraparticles with Tunable Hierarchical Porosity - Egly, Steffen; Fröhlich, Christina; Vogel, Stefanie; Grünewald, Alina; Wang, Junwei; Detsch, Rainer; Boccaccini, Aldo R.; Vogel, Nicolas (Langmuir, 2018)
We investigate the formation of spherical supraparticles with controlled and tunable porosity on the nanometer and micrometer scales using the self-organization of a binary mixture of small (nanometer scale) oxidic particles with large (micrometer scale) polystyrene particles in the confinement of an emulsion droplet. The external confinement determines the final, spherical structure of the hybrid assembly, while the small particles form the matrix material. The large particles act as templating porogens to create micropores after combustion at elevated temperatures. We control the pore sizes on the micrometer scale by varying the size of the coassembled polystyrene microspheres and produce supraparticles from both silica- and calcium-containing CaO/SiO2 particles. Although porous supraparticles are obtained in both cases, we found that the presence of calcium ions substantially complicated the fabrication process since the increased ionic strength of the dispersion compromises the colloidal stability during the assembly process. We minimized these stability issues via the addition of a steric stabilizing agent and by mixing bioactive and silica colloidal particles. We investigated the interaction of the porous particles with bone marrow stromal cells and found an increase in cell attachment with increasing pore size of the self-assembled supraparticles.

Bovine Serum Albumin (BSA)/polyacrylonitrile (PAN) biohybrid nanofibers coated with a biomineralized calcium deficient hydroxyapatite (HA) shell for wound dressing - Homaeigohar, Shahin; Tsai, Ting Yu; Zarie, Eman S.; Elbahri, Mady; Young, Tai Horng; Boccaccini, Aldo R. (Materials Science and Engineering C, 2020)
Here, for the first time, a nanofibrous (NF) wound dressing comprising biomineralized polyacrylonitrile (PAN) nanofibers is developed. In contrast to the majority of the currently available nanofibrous wound dressings that are based on natural polymers, PAN is a synthetic, industrial polymer, which has been rarely considered for this purpose. PAN NFs are first hydrolyzed to allow for tethering of biofunctional agents (here Bovine Serum Albumin (BSA)). Later, the biofunctionlized PAN NFs are biomineralized by immersion in simulated body fluid (SBF). As a result, core-shell, calcium deficient hydroxyapatite (HA)/BSA/PAN nanofibers form, that are mechanically stronger (elastic modulus; 8.5 vs. 6 MPa) compared to the untreated PAN NFs. The biomineralized PAN NFs showed promising bioactivity as reflected in the cell biology tests with fibroblast and keratinocyte cells. Hs68 fibroblasts and HaCat keratinocytes were found to be more viable in the presence of the biomineralized NFs than when they were co-cultured with the neat PAN NFs. Such mechanical and biological characteristics of the biomineralized PAN NFs are favorable for wound dressing applications.
CRIS-Team Scopus Importer:2020-07-24
Keywords: Biofunctionalization; Biomineralization; Nanofiber; Polyacrylonitrile (PAN); Wound dressing

Bovine serum albumin-modified 3D printed alginate dialdehyde-gelatin scaffolds incorporating polydopamine/SiO2-CaO nanoparticles for bone regeneration - Kim, Myong-Ho; Schöbel, Lisa; Geske, Michael; Boccaccini, Aldo R.; Ghorbani, Farnaz (International Journal of Biological Macromolecules, 2024)
Three-dimensional (3D) printing allows precise manufacturing of bone scaffolds for patient-specific applications and is one of the most recently developed and implemented technologies. In this study, bilayer and multimaterial alginate dialdehyde-gelatin (ADA-GEL) scaffolds incorporating polydopamine (PDA)/SiO2-CaO nanoparticle complexes were 3D printed using a pneumatic extrusion-based 3D printing technology and further modified on the surface with bovine serum albumin (BSA) for application in bone regeneration. The morphology, chemistry, and in vitro bioactivity of PDA/SiO2-CaO nanoparticle complexes were characterized (n = 3) and compared with those of mesoporous SiO2-CaO nanoparticles. Successful deposition of the PDA layer on the surface of the SiO2-CaO nanoparticles allowed better dispersion in a liquid medium and showed enhanced bioactivity. Rheological studies (n = 3) of ADA-GEL inks consisting of PDA/SiO2-CaO nanoparticle complexes showed results that may indicate better injectability and printability behavior compared to ADA-GEL inks incorporating unmodified nanoparticles. Microscopic observations of 3D printed scaffolds revealed that PDA/SiO2-CaO nanoparticle complexes introduced additional topography onto the surface of 3D printed scaffolds. Additionally, the modified scaffolds were mechanically stable and elastic, closely mimicking the properties of natural bone. Furthermore, protein-coated bilayer scaffolds displayed controllable absorption and biodegradation, enhanced bioactivity, MC3T3-E1 cell adhesion, proliferation, and higher alkaline phosphatase (ALP) activity (n = 3) compared to unmodified scaffolds. Consequently, the present results confirm that ADA-GEL scaffolds incorporating PDA/SiO2-CaO nanoparticle complexes modified with BSA offer a promising approach for bone regeneration applications.
CRIS-Team Scopus Importer:2024-03-22
Keywords: 3D printing; Alginate dialdehyde-gelatin; Bovine serum albumin; Polydopamine; Silica-calcia; Tissue engineering

Calcium phosphate-based composites as injectable bone substitute materials - Low, Kah Ling; Tan, Soon Huat; Zein, Sharif Hussein Sharif; Roether, Judith A.; Mourino, Viviana; Boccaccini, Aldo R. (Journal of Biomedical Materials Research Part B-Applied Biomaterials, 2010)
A major weakness of current orthopedic implant materials, for instance sintered hydroxyapatite (HA), is that they exist as a hardened form, requiring the surgeon to fit the surgical site around an implant to the desired shape. This can cause an increase in bone loss, trauma to the surrounding tissue, and longer surgical time. A convenient alternative to harden bone filling materials are injectable bone substitutes (IBS). In this article, recent progress in the development and application of calcium phosphate (CP)-based composites use as IBS is reviewed. CP materials have been used widely for bone replacement because of their similarity to the mineral component of bone. The main limitation of bulk CP materials is their brittle nature and poor mechanical properties. There is significant effort to reinforce or improve the mechanical properties and injectability of calcium phosphate cement (CPC) and this review resumes different alternatives presented in this specialized literature. © 2010 Wiley Periodicals, Inc.
UnivIS-Import:2015-03-09:Pub.2010.tech.IW.LM.calciu
Keywords: Additives; Bone; Calcium phosphate cement; Injectability; Injectable bone substitutes; Mechanical properties

Calcium supplementation of bioinks reduces shear stress-induced cell damage during bioprinting - Fischer, Lena; Nosratlo, Mojtaba; Hast, Katharina; Karakaya, Emine; Ströhlein, Nadi; Esser, Tilman; Gerum, Richard; Richter, Sebastian; Engel, Felix; Detsch, Rainer; Fabry, Ben; Thievessen, Ingo (Biofabrication, 2022)
During bioprinting, cells are suspended in a viscous bioink and extruded under pressure through small diameter printing needles. The combination of high pressure and small needle diameter exposes cells to considerable shear stress, which can lead to cell damage and death. Approaches to monitor and control shear stress-induced cell damage are currently not well established. To visualize the effects of printing-induced shear stress on plasma membrane integrity, we add FM 1-43 to the bioink, a styryl dye that becomes fluorescent when bound to lipid membranes, such as the cellular plasma membrane. Upon plasma membrane disruption, the dye enters the cell and also stains intracellular membranes. Extrusion of alginate-suspended NIH/3T3 cells through a 200 mu m printing needle led to an increased FM 1-43 incorporation at high pressure, demonstrating that typical shear stresses during bioprinting can transiently damage the plasma membrane. Cell imaging in a microfluidic channel confirmed that FM 1-43 incorporation is caused by cell strain. Notably, high printing pressure also impaired cell survival in bioprinting experiments. Using cell types of different stiffnesses, we find that shear stress-induced cell strain, FM 1-43 incorporation and cell death were reduced in stiffer compared to softer cell types and demonstrate that cell damage and death correlate with shear stress-induced cell deformation. Importantly, supplementation of the suspension medium with physiological concentrations of CaCl2 greatly reduced shear stress-induced cell damage and death but not cell deformation. As the sudden influx of calcium ions is known to induce rapid cellular vesicle exocytosis and subsequent actin polymerization in the cell cortex, we hypothesize that calcium supplementation facilitates the rapid resealing of plasma membrane damage sites. We recommend that bioinks should be routinely supplemented with physiological concentrations of calcium ions to reduce shear stress-induced cell damage and death during extrusion bioprinting.
CRIS-Team WoS Importer:2022-08-26

Calorimetric approach to assess the apatite-forming capacity of bioactive glasses - Zine Elabidine, Mohamed; Cherbib, Mohamed Atef; Khattech, Ismail; Bechrifa, Ali; Schuhladen, Katharina; Brauer, Delia S.; Boccaccini, Aldo R. (Journal of Non-Crystalline Solids, 2020)
This paper investigates a new microcalorimetric approach to assess the capacity of bioactive glasses, to form hydroxyapatite during immersion in physiological fluids. Three silicate glasses were selected namely 45S5 (46.1SiO2-2.6P2O5-26.9CaO-24.4Na2O; mol%), F0 (46.1SiO2-2.6P2O5-37.6CaO-6.8Na2O-6.8K2O; mol%), and F3 (44.8SiO2-2.5P2O5-36.5CaO-6.6Na2O-6.6K2O-3.0CaF2; mol%), synthesized by a melt-quench route and studied initially using electron microscopy. The hydroxyapatite formation of samples immersed in simulated body fluid (SBF) was monitored using X-ray diffraction and Infrared spectroscopy. The microcalorimetric investigations were conducted by observing, over seven days, the thermochemical behavior of glasses in SBF at 37°C and by measuring the heat of acidic dissolution of treated and untreated samples in SBF. The results showed that the samples with the higher capacity to form apatites also present the higher heat variation from day-to-day, with 45S5 presenting the highest heat difference recorded in both experiments. These analyses led to the quantification of the calcium phosphate formed for each bioactive glass composition.
CRIS-Team Scopus Importer:2020-10-16
Keywords: Apatite; Bioactive glass; Bioactivity; Microcalorimetry; Thermochemistry

Cancer research by means of tissue engineering - is there a rationale? - Horch, Raymund E.; Boos, Anja; Yuan, Quan; Bleiziffer, Oliver; Detsch, Rainer; Boccaccini, Aldo R.; Alexiou, Christoph; Sun, Jiaming; Beier, Justus; Arkudas, Andreas (Journal of Cellular and Molecular Medicine, 2013)
Tissue engineering (TE) has evoked new hopes for the cure of organ failure and tissue loss by creating functional substitutes in the laboratory. Besides various innovations in the context of Regenerative Medicine (RM), TE also provided new technology platforms to study mechanisms of angiogenesis and tumour cell growth as well as potentially tumour cell spreading in cancer research. Recent advances in stem cell technology - including embryonic and adult stem cells and induced pluripotent stem cells - clearly show the need to better understand all relevant mechanisms to control cell growth when such techniques will be administered to patients. Such TE-Cancer research models allow us to investigate the interactions that occur when replicating physiological and pathological conditions during the initial phases of replication, morphogenesis, differentiation and growth under variable given conditions. Tissue microenvironment has been extensively studied in many areas of TE and it plays a crucial role in cell signalling and regulation of normal and malignant cell functions. This article is intended to give an overview on some of the most recent developments and possible applications of TE and RM methods with regard to the improvement of cancer research with TE platforms. The synthesis of TE with innovative methods of molecular biology and stem-cell technology may help investigate and potentially modulate principal phenomena of tumour growth and spreading, as well as tumour-related angiogenesis. In the future, these models have the potential to investigate the optimal materials, culture conditions and material structure to propagate tumour growth. © 2013 The Authors.
UnivIS-Import:2015-03-09:Pub.2013.tech.IW.LM.cancer
Keywords: Angiogenesis; AV loop; Cancer research; Cell transplantation; in vitro tumour models; Metastasis; Telocytes; Tissue engineering; Tumour cells; Tumour growth; Tumourgenesis

Carbon nanotube coatings on Bioglass-Based tissue engnineering scaffolds - Boccaccini, Aldo R.; et al. (Advanced Functional Materials, 2007)
UnivIS-Import:2015-03-09:Pub.2007.tech.IW.LM.carbon

Carbon nanotube composite scaffolds and coatings for tissue engineering applications - Boccaccini, Aldo R.; Gerhardt, Lutz-Christian (Key Engineering Materials, 2010)
This review aimed at summarising the current knowledge on materials science aspects of carbon nanotube composites for tissue engineering applications. On the basis of literature data presented in this review, the following main conclusions can be drawn: 1. Carbon nanotubes can be successfully incorporated into inorganic ceramics, as well as in natural and synthetic polymer matrices by means of a broad range of techniques including solvent casting, electrospinning, thermally-induced phase separation and gelation processes. 2. CNT coatings can be obtained on 3D scaffolds (made of polymers or bioceramics) by electrophoretic deposition technique, leading to homogeneous covering of the pore structure by CNTs. 3. Due to the physical nature of CNTs, both structural and surface compatibility of tissue engineering scaffolds can be improved. Surface chemical functionalisation of CNTs is an attractive approach to homogenise the dispersion of CNTs throughout the matrix, thereby positively influencing the interfacial bonding strength, mechanical and electrical properties of the scaffolds. 4. The electrical conductivity of CNT containing composites can be further increased by mechanically induced alignment of the composite so that an anisotropically directed stimulation of electrically excitable recipient tissues is possible. 5. The incorporation of CNTs into polymer matrices imparts not only nano-roughness to the surface of the composites, resulting in favourable physico-chemical (e.g. antithrombotic) properties and positive effects on protein and cell adsorption, but also affects the polymer stability allowing the control and fine-tuning of degradations kinetics and characteristics of biodegradable polymer/CNT composites. 6. In the case of bioactive glass scaffolds, the in vitro bioactivity of bioactive glasses is maintained in the presence of CNTs and in vivo bone growth (mineralisation) and neovascularisation can even be improved by the addition of CNTs in tissue engineering scaffolds. 7. The results of the studies reviewed in this paper demonstrate that tailored CNTs-filled composites have a high potential for applications in tissue engineering and regenerative medicine for regeneration of diseased or damaged soft and hard tissues. The safe use of CNTs as part of TE strategies should thus be of great benefit to develop new generation scaffolds with enhanced in-vitro and in-vivo performance. The analysis of the available literature has revealed that in addition to improving the dispersion of CNTs in matrices and positively influencing composite interphases, functionalisation of CNTs also influences the degree of possible toxicity of CNTs [18]. Functionalisation may therefore be a key parameter for controlling the impact of CNTs on human health and the environment, requiring further interdisciplinary-driven studies and interplay of various disciplines ranging from materials science to biology. Integrating nanotoxicology with a life-cycle perspective will therefore be a prerequisite for the development of nanotechnology-based applications of CNTs in a safe and responsible manner [32]. © (2010) Trans Tech Publications.
UnivIS-Import:2015-03-09:Pub.2010.tech.IW.LM.carbon
Keywords: Bone; Carbon nanotubes; Cardiac muscle; Cartilage; Coatings; Composites; Connective tissue; Endothelial tissue; Neural tissue; Scaffolds; Tissue engineering

Carbon nanotube deposits and CNT/SiO2 composite coatings by electrophoretic deposition - Boccaccini, Aldo R.; et al. (Advances in Applied Ceramics, 2007)
Multiwalled carbon nanotube (CNT) films have been successfully fabricated by electrophoretic deposition (EPD) on stainless steel substrates. Electrophoretic deposition was performed using optimised aqueous suspensions under constant voltage conditions. Triton X-100 was used as a surfactant to disperse CNT bundles, and iodine was added as a particle charger. CNT/SiO2 composite coatings were prepared by electrophoretic co-deposition. Experimental results show that the CNTs were efficiently mixed with SiO2 nanoparticles to form a network structure. Layered CNT/SiO2 porous composites were obtained by sequential EPD experiments alternating the deposition of CNT and SiO2 nanoparticles. The structure of all films deposited was studied in detail by scanning electron microscopy. Possible applications of CNT and CNT/SiO2 films are as porous coatings in the biomedical field, thermal management devices, biomedical sensors and other functional applications where the properties of CNTs are required. © 2007 Institute of Materials, Minerals and Mining.
UnivIS-Import:2015-03-09:Pub.2007.tech.IW.LM.carbon_7
Keywords: Carbon nanotubes; Ceramic matrix composites; Coatings; Electrophoretic deposition; Silica nanoparticles

Carbon nanotube-nanocrystal heterostructures fabricated by electrophoretic deposition - Mahajan, S. V.; Hasan, S. A.; Cho, J.; Shaffer, M. S. P.; Boccaccini, Aldo R.; Dickerson, J. H. (Nanotechnology, 2008)
Alternating layer, carbon nanotubes-nanocrystal composite films, comprising multi-walled carbon nanotubes (MWCNTs) and iron oxide (Fe3O 4) nanocrystals, have been fabricated via electrophoretic deposition (EPD) on stainless steel and gold substrates. Low field-high current and high field-low current EPD schemes were integrated to produce the composite films. The low field-high current EPD approach produced porous mats from an aqueous suspension of the MWCNTs, while the high field-low current EPD approach produced tightly packed nanocrystal films from a dispersion of the nanocrystals in hexane. Large electric fields applied during the nanocrystal EPD and strong van der Waals interactions among the nanocrystals facilitated the formation of tightly packed nanocrystal films atop the MWCNT mats to create CNT mat-nanocrystal film composites. The surface coverage and homogeneity of the nanocrystal films improved with repeated deposition of the nanocrystals on the same mat. The assembly of nanotube mats on top of the CNT mat-nanocrystal film composite confirmed the feasibility of multilayered CNT mat-nanocrystal film heterostructures suitable for a range of devices. Scanning electron microscopy (SEM) and atomic force microscopy (AFM) techniques were employed to characterize the surface coverage, homogeneity, and topology of these composite films. © IOP Publishing Ltd.
UnivIS-Import:2015-03-09:Pub.2008.tech.IW.LM.carbon_5

Carbon nanotubes: do they toughen brittle matrices? - Cho, Johann; Inam, Fawad; Reece, Mike J.; Chlup, Zdenek; Dlouhy, Ivo; Shaffer, Milo S. P.; Boccaccini, Aldo R. (Journal of Materials Science, 2011)
The development of a model CNT-brittle matrix composite system, based on SiO2 glass containing well-dispersed CNTs at up to 15 wt%, allows a direct assessment of the effect of the nanoscale filler on fracture toughness (KIC). Samples were prepared by colloidal heterocoagulation followed by spark plasma sintering. Detailed KIC measurements, using both indentation and notched beam techniques, show a linear improvement with CNT content, with up to a twofold increase of fracture toughness at maximum loading. The results from the two methods used in this study show equivalent trends but differing absolute values; the relative merits of these two approaches to measuring nanocomposite toughness are compared. Possible toughening mechanisms associated with CNT pull-out, crack bridging, and crack deflection are identified, and discussed quantitatively, drawing on conventional short-fibre composite theory and the potential effects of scaling fibre diameter. © Springer Science+Business Media, LLC 2011.
UnivIS-Import:2015-03-09:Pub.2011.tech.IW.LM.carbon

Carbon nanotube-SiO2 composites by colloidal processing - Arvanitelis, C.; Jayaseelan, D. D.; Cho, J.; Boccaccini, Aldo R. (Advances in Applied Ceramics, 2008)
The surfactants assisted colloidal processing of 1.0 wt-% carbon nanotube (CNT)-SiO2 composites using acid treated CNTs and colloidal silica has been investigated. By using different combinations of anionic and cationic surfactants five systems were developed with the aim of coating the CNTs with silica particles and creating a homogenously dispersed composite. Sintering of CNT-SiO2 composites was performed for 3 h at 1300°C in argon atmosphere. Pressureless sintering yielded composites with a density >95% of the theoretical. X-ray diffraction analysis showed the presence of cristobalite, but no other crystalline phases were detected in the sintered composites. Microstructural observation revealed isolated CNTs in the SiO2 matrix both in the as dried powder and in the sintered samples. It is concluded that the simple colloidal process developed here can be a convenient alternative to the sol-gel based methods used for fabrication of inorganic matrix composites containing CNTs. © 2008 Institute of Materials, Minerals and Mining.
UnivIS-Import:2015-03-09:Pub.2008.tech.IW.LM.carbon
Keywords: Carbon nanotubes; Colloidal processing; Silica matrix composites; Surfactants

Cell adhesion evaluation of laser-sintered HAp and 45S5 bioactive glass coatings on micro-textured zirconia surfaces using MC3T3-E1 osteoblast-like cells - Mesquita-Guimarães, J.; Detsch, Rainer; Souza, A. C.; Henriques, B.; Silva, F. S.; Boccaccini, Aldo R.; Carvalho, O. (Materials Science and Engineering C, 2020)
Laser texturing is a technique that has been increasingly explored for the surface modification of several materials on different applications. Laser texturing can be combined with conventional coating techniques to functionalize surfaces with bioactive properties, stimulating cell differentiation and adhesion. This study focuses on the cell adhesion of laser-sintered coatings of hydroxyapatite (HAp) and 45S5 bioactive glass (45S5 BG) on zirconia textured surfaces using MC3T3-E1 cells. For this purpose, zirconia surfaces were micro-textured via laser and then coated with HAp and 45S5 BG glass via dip coating. Afterwards, the bioactive coatings were laser sintered, and a reference group of samples was conventionally sintering. The cell adhesion characterisation was achieved by cell viability performing live/dead analysis using fluorescence stains and by SEM observations for a qualitative analysis of cell adhesion. The in vitro results showed that a squared textured pattern with 100 μm width grooves functionalized with a bioactive coating presented an increase of 90% of cell viability compared to flat surfaces after 48 h of incubation. The functionalized laser sintered coatings do not present significant differences in cell viability when compared to conventionally sintered coatings. Therefore, the results reveal that laser sintering of HAp and 45S5 BG coatings is a fast and attractive coating technique.
CRIS-Team Scopus Importer:2020-01-21
Keywords: 45S5 bioactive glass; Cell-cell contacts; Hydroxyapatite; Laser sintering; Laser surface texturing; MC3T3-E1

Cell Interactions with Size-Controlled Colloidal Monolayers: Toward Improved Coatings in Bone Tissue Engineering - Walter, Teresa; Grünewald, Alina; Detsch, Rainer; Boccaccini, Aldo R.; Vogel, Nicolas (Langmuir, 2020)
The surface structure of biomaterials is of key importance to control its interactions with biological environments. Industrial fabrication and coating processes often introduce particulate nanostructures at implant surfaces. Understanding the cellular interaction with particle-based surface topologies and feature sizes in the colloidal length scale therefore offers the possibility to improve the biological response of synthetic biomaterials. Here, surfaces with controlled topography and regular feature sizes covering the relevant length scale of particulate coatings (100-1000 nm) are fabricated by colloidal templating. Using fluorescent microscopy, WST assay, and morphology analysis, results show that adhesion and attachment of bone-marrow derived murine stromal cells (ST2) are strongly influenced by the surface feature size while geometric details play an insignificant role. Quantitative analysis shows enhanced cell adhesion, spreading, viability, and activity when surface feature size decreases below 200 nm compared to flat surfaces, while larger feature sizes are detrimental to cell adhesion. Kinetic studies reveal that most cells on surfaces with larger features lose contact with the substrate over time. This study identifies colloidal templating as a simple method for creating highly defined model systems to investigate complex cell functions and provides design criteria for the choice of particulate coatings on commercial implant materials.
CRIS-Team Scopus Importer:2020-03-17

Cell-laden alginate dialdehyde–gelatin hydrogels formed in 3D printed sacrificial gel - Dranseikiene, Dalia; Schrüfer, Stefan; Schubert, Dirk W.; Reakasame, Supachai; Boccaccini, Aldo R. (Journal of Materials Science: Materials in Medicine, 2020)
Alginate dialdehyde–gelatin (ADA–GEL) hydrogels have been reported to be suitable matrices for cell encapsulation. In general, application of ADA–GEL as bioink has been limited to planar structures due to its low viscosity. In this work, ring shaped constructs of ADA–GEL hydrogel were fabricated by casting the hydrogel into sacrificial molds which were 3D printed from 9% methylcellulose and 5% gelatin. Dissolution of the supporting structure was observed during the 1st week of sample incubation. In addition, the effect of different crosslinkers (Ba2+ and Ca2+) on the physicochemical properties of ADA–GEL and on the behavior of encapsulated MG-63 cells was investigated. It was found that Ba2+ crosslinked network had more than twice higher storage modulus, and mass decrease to 70% during incubation compared to 42% in case of hydrogels crosslinked with Ca2+. In addition, faster increase in cell viability during incubation and earlier cell network formation were observed after Ba2+ crosslinking. No negative effects on cell activity due to the use of sacrificial materials were observed. The approach presented here could be further developed for cell-laden ADA–GEL bioink printing into complex 3D structures. [Figure not available: see fulltext.].
CRIS-Team Scopus Importer:2020-03-27

Cell laden alginate-keratin based composite microcapsules containing bioactive glass for tissue engineering applications. - Reakasame, Supachai; Trapani, Daniela; Detsch, Rainer; Boccaccini, Aldo R. (Journal of Materials Science: Materials in Medicine, 2018)
Microcapsules based on alginate-keratin, alginate dialdehyde (ADA)-keratin and ADA-keratin-45S5 bioactive glass (BG) were successfully prepared. The samples were characterized by light microscopy, scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR). The results showed that ADA-based materials possess higher degradation rate compared to alginate-based materials. The incorporation of BG particles (mean particle size: 2.0 µm) improved the bioactivity of the materials. Moreover, the biological properties of the samples were evaluated by encapsulating MG-63 osteosarcoma cells into the microcapsules. The cell viability in all samples increased during 21 days of cultivation. However, the presence of 0.5% BG particle seemed to have initial negative effect on cell growth compared to other samples without BG. On the other hand, the positive effect of CaP formation was visible after 3 weeks in the BG containing samples. The results are relevant to consider the development of cell laden bioinks incorporating inorganic bioactive particles for biofabrication approaches.

Cell specificity of magnetic cell seeding approach to hydrogel colonization - Singh, Raminder; Wieser, Anna; Reakasame, Supachai; Detsch, Rainer; Dietel, Barbara; Alexiou, Christoph; Boccaccini, Aldo R.; Cicha, Iwona (Journal of Biomedical Materials Research Part A, 2017)
Keywords: alginate-based hydrogels; endothelial cells; fibroblasts; magnetic cell seeding; superparamagnetic iron oxide nanoparticles

Cellular behaviour of bone marrow stromal cells on modified Ti-Nb surfaces - Urena, Julia Maria; Tsipas, Sophia Alexandra; Jimenez-Morales, A.; Gordo, E.; Detsch, Rainer; Boccaccini, Aldo R. (Materials & Design, 2018)
Keywords: Bone mineralization; Osteogenic differentiation; Powder technology; Surface modification; β-gradient titanium

Cellular Response to Sol-Gel Hybrid Materials Releasing Boron and Calcium Ions - Coelho, Soraia Alexandra Ramos; Almeida, Jose Carlos; Ünalan, Irem; Detsch, Rainer; Miranda Salvado, Isabel Margarida; Boccaccini, Aldo R.; Fernandes, Maria Helena Vaz (ACS Biomaterials Science and Engineering, 2021)
Poly(dimethylsiloxane) (PDMS)-SiO2-CaO-based hybrid materials prepared by sol-gel have proved to be very promising materials for tissue engineering applications and drug-delivery systems. These hybrids are biocompatible and present osteogenic and bioactive properties supporting osteoblast attachment and bone growth. The incorporation of therapeutic elements in these materials, such as boron (B) and calcium (Ca), was considered in this study as an approach to develop biomaterials capable of stimulating bone regeneration. The main purpose of this work was thus to produce, by sol-gel, bioactive and biocompatible hybrid materials of the PDMS-SiO2-B2O3-CaO system, capable of a controlled Ca and B release. Different compositions with different boron amounts were prepared using the same precursors resulting in different monolithic materials, with distinct structures and microstructures. Structural features were assessed by Fourier transform infrared (FT-IR) spectrometry and solid-state nuclear magnetic resonance (NMR) techniques, which confirmed the presence of hybrid bonds (Si-O-Si) between organic (PDMS) and inorganic phase (tetraethyl orthosilicate (TEOS)), as well as borosiloxane bonds (B-O-Si). From the 11B NMR results, it was found that Ca changes the boron coordination, from trigonal (BO3) to tetrahedral (BO4). Scanning electron microscopy (SEM) micrographs and N2 isotherms showed that the incorporation of boron modifies the material's microstructure by increasing the macroporosity and decreasing the specific surface area (SSA). In vitro tests in simulated body fluid (SBF) showed the precipitation of a calcium phosphate layer on the material surface and the controlled release of therapeutic ions. The cytocompatibility of the prepared hybrids was studied with bone marrow stromal cells (ST-2 cell line) by analyzing the cell viability and cell density. The results demonstrated that increasing the dilution rate of extraction medium from the hybrids leads to improved cell behavior. The relationship between the in vitro response and the structural and microstructural features of the materials was explored. It was shown that the release of calcium and boron ions, determined by the hybrid structure was crucial for the observed cells behavior. Although not completely understood, the encouraging results obtained constitute an incentive for further studies on this topic.
CRIS-Team Scopus Importer:2021-02-26
Keywords: bioactivity; boron; calcium; cytocompatibility; hybrids; sol-gel; structure

Cellulose-based bilayer films with asymmetric properties for the sealing of tissue lesions - Gürer, Ufuk; Mansi, Salma; Reuter, Malin; Arcuti, Dario; Hadzhieva, Zoya; Günsel, Umut; Hagn, Franz; Boccaccini, Aldo R.; Mela, Petra; Lieleg, Oliver (Cellulose, 2025)
To be able to support the complex process of wound closure, a biocompatible material is required that combines suitable adhesiveness and stability with the ability to withstand certain biological challenges such as biofouling while avoiding undesired side effects i.e., hemolysis. Here, we present an asymmetrically designed, cellulose-based bilayer film that satisfies all those requirements and can be produced in a simple and environmentally friendly manner. The wound-facing side of this film features excellent adhesive properties brought about by a biocompatible catechol functionalization of carboxymethyl cellulose and promotes blood coagulation while avoiding hemolysis. In contrast, the outer side of the film has bacteria-repellent properties, which are established by the anti-bacterial glycoprotein mucin, integrated into a fibrous cellulose matrix, that can be covalently crosslinked. In addition, the construct can act as a drug reservoir and decomposes in a wet environment. These properties render the bilayer film a promising candidate for applications in wound closure, particularly for lesions encountered in intestinal or ocular tissues.
CRIS-Team Scopus Importer:2025-04-01
Keywords: Antibacterial; Coagulation; Electrospinning; Mucin; Ocular damage; Wound closure

Cellulose Nanocrystals-Bioactive Glass Hybrid Coating as Bone Substitutes by Electrophoretic Co-deposition: In Situ Control of Mineralization of Bioactive Glass and Enhancement of Osteoblastic Performance - Chen, Qiang; Perez Garcia, Rosalina; Munoz, Josemari; Perez De Larraya, Uxua; Garmendia, Nere; Yao, Qingqing; Boccaccini, Aldo R. (ACS Applied Materials and Interfaces, 2015)
Surface functionalization of orthopedic implants is being intensively investigated to strengthen bone-to-implant contact and accelerate bone healing process. A hybrid coating, consisting of 45S5 bioactive glass (BG) individually wrapped and interconnected with fibrous cellulose nanocrystals (CNCs), is deposited on 316L stainless steel from aqueous suspension by a one-step electrophoretic deposition (EPD) process. Apart from the codeposition mechanism elucidated by means of zeta-potential and scanning electron microscopy measurements, in vitro characterization of the deposited CNCs-BG coating in simulated body fluid reveals an extremely rapid mineralization of BG particles on the coating (e.g., the formation of hydroxyapatite crystals layer after 0.5 day). A series of comparative trials and characterization methods were carried out to comprehensively understand the mineralization process of BG interacting with CNCs. Furthermore, key factors for satisfying the applicability of an implant coating such as coating composition, surface topography, and adhesion strength were quantitatively investigated as a function of mineralization time. Cell culture studies (using MC3T3-E1) indicate that the presence of CNCs-BG coating substantially accelerated cell attachment, spreading, proliferation, differentiation, and mineralization of extracellular matrix. This study has confirmed the capability of CNCs to enhance and regulate the bioactivity of BG particles, leading to mineralized CNCs-BG hybrids for improved bone implant coatings.
Keywords: bioactive glass; electrophoresis; guided mineralization; hybrid materials; nanocellulose

Centrifugal spinning of polyvinyl alcohol/sodium alginate-di -aldehyde-gelatin based antibacterial nanofibers intended for skin tissue engineering - Akhtar, Memoona; Ahmed, Sheraz; Hussain, Rabia; Wadood, Abdul; Roy, Ipsita; Atiq Ur Rehman, Muhammad; Boccaccini, Aldo R. (Materials Letters, 2022)
In this study, three types of nanofibers, i.e. polyvinyl alcohol (PVA), alginate di-aldehyde (ADA)/PVA, and ADA-gelatin (GEL)/PVA, were fabricated via centrifugal spinning. The spinability of ADA was improved by mixing with PVA. Furthermore, GEL and sesame oil were added in the ADA solution to control the degradation kinetics and to improve the viscosity of the solution, respectively. Later, the solution was fed to a rotating spinneret (3000 rpm at 250 °C) which led to the fabrication of nanofibers. The developed nanofibers were loaded with copper-silver (Cu-Ag) doped mesoporous bioactive glass nanoparticles (MBGNs) to provide therapeutic effects (antibacterial effect). Scanning electron microscopy images showed that the nanofiber diameters were 139 ± 62 nm, 258 ± 42 nm, and 281 ± 34 nm, for PVA, ADA/PVA, and ADA-GEL/PVA respectively, with web-like morphology. Fourier transform infrared spectroscopy confirmed the presence of chemical bonds attributed to the ADA, GEL, and PVA components. The results of the inhibition halo test confirmed that the nanofibers (ADA-GEL/PVA & ADA/PVA) exhibit potent antibacterial effect against Staphylococcus aureus and Escherichia coli.
CRIS-Team Scopus Importer:2022-06-17
Keywords: Bioceramics; Biomaterials; Fibre technology

Ceramic matrix composites containing carbon nanotubes - Cho, Johann; Boccaccini, Aldo R.; Shaffer, Milo S. P. (Journal of Materials Science, 2009)
Due to the remarkable physical and mechanical properties of individual, perfect carbon nanotubes (CNTs), they are considered to be one of the most promising new reinforcements for structural composites. Their impressive electrical and thermal properties also suggest opportunities for multifunctional applications. In the context of inorganic matrix composites, researchers have particularly focussed on CNTs as toughening elements to overcome the intrinsic brittleness of the ceramic or glass material. Although there are now a number of studies published in the literature, these inorganic systems have received much less attention than CNT/polymer matrix composites. This paper reviews the current status of the research and development of CNT-loaded ceramic matrix composite (CMC) materials. It includes a summary of the key issues related to the optimisation of CNT-based composites, with particular reference to brittle matrices and provides an overview of the processing techniques developed to optimise dispersion quality, interfaces, and density. The properties of the various composite systems are discussed, with an emphasis on toughness; a comprehensive comparative summary is provided, together with a discussion of the possible toughening mechanism that may operate. Last, a range of potential applications are discussed, concluding with a discussion of the scope for future developments in the field. © 2009 Springer Science+Business Media, LLC.
UnivIS-Import:2015-03-09:Pub.2009.tech.IW.LM.cerami

Ceramics and Composites Processing Methods - Bansal, Narottam; Boccaccini, Aldo R. (John Wiley and Sons, 2012)
Examines the latest processing and fabrication methods. There is increasing interest in the application of advanced ceramic materials in diverse areas such as transportation, energy, environmental protection and remediation, communications, health, and aerospace. This book guides readers through a broad selection of key processing techniques for ceramics and their composites, enabling them to manufacture ceramic products and components with the properties needed for various industrial applications. With chapters contributed by internationally recognized experts in the field of ceramics, the book includes traditional fabrication routes as well as new and emerging approaches in order to meet the increasing demand for more reliable ceramic materials. Ceramics and Composites Processing Methods is divided into three sections: Densification, covering the fundamentals and practice of sintering, pulsed electric current sintering, and viscous phase silicate processing. Chemical Methods, examining colloidal methods, sol-gel, gel casting, polymer processing, chemical vapor deposition, chemical vapor infiltration, reactive melt infiltration, and combustion synthesis. Physical Methods, including directional solidification, solid free-form fabrication, microwave processing, electrophoretic deposition, and plasma spraying. Each chapter focuses on a particular processing method or approach. Collectively, these chapters offer readers comprehensive, state-of-the-science information on the many approaches, techniques, and methods for the processing and fabrication of advanced ceramics and ceramic composites. With its coverage of the latest processing methods, Ceramics and Composites Processing Methods is recommended for researchers and students in ceramics, materials science, structural materials, biomedical engineering, and nanotechnology. © 2012 The American Ceramic Society.

Ceramics for environmental and energy applications II - Dogan, Fatih; Tritt, Terry M.; Sekino, Tohru; Katoh, Yutai; Pyzik, Aleksander J.; Belharouak, Ilias; Boccaccini, Aldo R.; Marra, James; Lin, Hua Tay (wiley, 2014)
A collection of papers from the below symposia held during the 10th Pacific Rim Conference on Ceramic and Glass Technology (PacRim10), June 2-7, 2013, in Coronado, California 2012: Solid Oxide Fuel Cells and Hydrogen Technology Direct Thermal to Electrical Energy Conversion Materials and Applications Photovoltaic Materials and Technologies Ceramics for Next Generation Nuclear Energy Advances in Photocatalytic Materials for Energy and Environmental Applications Ceramics Enabling Environmental Protection: Clean Air and Water Advanced Materials and Technologies for Electrochemical Energy Storage Systems Glasses and Ceramics for Nuclear and Hazardous Waste Treatment.
CRIS-Team Scopus Importer:2022-08-05

Ceramic Transactions: Preface - Dogan, Fatih; Tritt, Terry M.; Sekino, Tohru; Katoh, Yutai; Pyzik, Aleksander J.; Belharouak, Ilias; Boccaccini, Aldo R.; Marra, James (Ceramics for Environmental and Energy Applications II - A Collection of Papers Presented at the 10th Pacific Rim Conference on Ceramic and Glass Technology, PacRim 2013, 2014)
CRIS-Team Scopus Importer:2022-08-05

Cerium and gallium containing mesoporous bioactive glass nanoparticles for bone regeneration: Bioactivity, biocompatibility and antibacterial activity - Kurtuldu, Fatih; Mutlu, Nurshen; Michálek, Martin; Zheng, Kai; Masar, Milan; Liverani, Liliana; Chen, Si; Galusek, Dušan; Boccaccini, Aldo R. (Materials Science and Engineering C, 2021)
In recent years, mesoporous bioactive glass nanoparticles (MBGNPs) have generated great attention in biomedical applications. In this study, cerium and gallium doped MBGNPs were prepared by microemulsion assisted sol-gel method in the binary SiO2-CaO system. MBGNPs with spheroidal and pineal shaped morphology were obtained. Nitrogen sorption analysis elucidated the mesoporous structure of synthesized nanoparticles with high specific surface area. X-ray diffraction analysis confirmed the amorphous nature of the nanoparticles. The chemical compositions of all samples were determined by inductively coupled plasma-optical emission spectrometry (ICP-OES), which revealed that the contents of cerium and gallium could be tailored by adjusting the concentrations of the precursors used for the synthesis. All MBGNPs exhibited in vitro bioactivity when immersed in simulated body fluid, except the particles doped with higher amounts than 1 mol% of cerium. MBGNPs showed antibacterial activity against S. aureus and E. coli without exhibiting cytotoxicity towards MG-63 osteoblast-like cells. Mentioned features of the obtained Ce and Ga-doped MBGNPs make them useful for multifunctional applications such as drug delivery carriers or bioactive fillers for bone tissue engineering applications.
CRIS-Team Scopus Importer:2021-04-16
Keywords: Antibacterial activity; Cerium; Gallium; Mesoporous bioactive glass nanoparticles; Sol-gel method

Cerium-Containing Bioactive Glasses Promote In Vitro Lymphangiogenesis - Xie, Hanyu; Sha, Sha; Lu, Lingbo; Wu, Geng; Jiang, Hongbing; Boccaccini, Aldo R.; Zheng, Kai; Xu, Rongyao (Pharmaceutics, 2022)
The lymphatic system is crucial for the regeneration of many tissues due to its fundamental role in immune cell trafficking, protein transport, and tissue homeostasis maintenance. Strategies stimulating lymphangiogenesis can provide new therapeutic approaches for tissue repair and regeneration (e.g., chronic wound healing). Here, we explored the effects of cerium-containing mesoporous bioactive glass nanoparticles (Ce-MBGNs) on lymphangiogenesis. The results showed that the extracts of Ce-MBGNs (1, 5, or 10 wt/v%) were non-cytotoxic toward lymphatic endothelial cells (LECs), while they enhanced the proliferation of LECs. Moreover, as evidenced by the scratch wound healing and Transwell migration assays, conditioned media containing the extract of Ce-MBGNs (1 wt/v%) could enhance the migration of LECs in comparison to the blank control and the media containing vascular endothelial growth factor-C (VEGF-C, 50 ng/mL). Additionally, a tube-formation assay using LECs showed that the extract of Ce-MBGNs (1 wt/v%) promoted lymphatic vascular network formation. Western blot results suggested that Ce-MBGNs could induce lymphangiogenesis probably through the HIF-1α/VEGFR-3 pathway. Our study for the first time showed the effects of Ce-MBGNs on stimulating lymphangiogenesis in vitro, highlighting the potential of Ce-MBGNs for wound healing.
CRIS-Team Scopus Importer:2022-01-28
Keywords: Bioactive glasses; Cerium; Lymphangiogenesis; Nanoparticles; Wound healing

Cerium doped dendritic mesoporous bioactive glass nanoparticles with bioactivity and drug delivery capability - Xu, Zhiyan; Keller, Emily; Beltrán, Ana M.; Zheng, Kai; Boccaccini, Aldo R. (Journal of Non-Crystalline Solids, 2023)
Dendritic mesoporous bioactive glass nanoparticles (DMBGNs) with unique three-dimensional structures are attracting increasing attention for biomedical applications. However, it is still challenging to tune the chemical composition of DMBGNs. In this work, we provide for the first time a feasible post-impregnation approach to incorporate metallic ions (Ca and Ce) into dendritic mesoporous silica nanoparticles, resulting in SiO2-CaO and SiO2-CaO-CeO2 (Ce-DMBGNs) without destroying the dendritic mesoporous topography. Both DMBGNs and Ce-DMBGNs were amorphous, negatively charged, with a hydrodynamic size of ∼200 nm. The synthesized DMBGNs and Ce-DMBGNs exhibited high bioactivity as evidenced by the rapid formation of hydroxyapatite (HA) after immersion in simulated body fluid (SBF) for 7 days. In addition, DMBGNs and Ce-DMBGNs showed high propolis loading efficiency and sustained release behavior. The results suggest that the developed Ce-DMBGNs have the potential to be used as a delivery vehicle of therapeutic ions and drugs in bone regeneration applications.
CRIS-Team Scopus Importer:2023-09-08
Keywords: Bioactive glass; Bioactivity; Cerium; Dendritic mesoporous nanoparticle; Drug delivery

Cerium-doped mesoporous bioactive glass nanoparticles reduce oxidative stress and adipogenic differentiation in human bone marrow-derived mesenchymal stromal cells - Jacobsen, V.; Kunisch, E.; Merle, C.; Xue, B.; Zheng, K.; Renkawitz, T.; Boccaccini, Aldo R.; Westhauser, F. (Journal of Trace Elements in Medicine and Biology, 2025)
Increased levels of reactive oxygen species (ROS) favor adipogenic over osteogenic differentiation in human bone-marrow derived mesenchymal stromal cells (BMSCs). Therefore, biomaterials containing ROS-suppressing elements such as Cerium (Ce) have been introduced to cell-based bone-tissue-engineering (BTE) approaches. This study was conducted to assess the efficacy of Ce-doped mesoporous bioactive glass nanoparticles (MBGNs) in reducing ROS levels and subsequently inhibiting the adipogenic differentiation of BMSCs. To this end, BMSCs were cultivated in adipogenesis inducing medium (AIM) and exposed to ions released from Ce-free MBGNs (composition in mol%: 86SiO2-14CaO), Low-Ce-MBGNs (composition in mol%: 86.6SiO2-12.1CaO-1.3CeO2) and High-Ce-MBGNs (composition in mol%: 86.0SiO2-11.8CaO-2.2CeO2). The influence of the different MBGNs on the expression of adipogenic and ROS-scavenging genes was assessed as well as their influence on lipid formation and the physical presence of ROS. Ce-MBGNs significantly reduced lipid production and the expression of adipogenic marker genes when compared to BMSCs cultivated in the presence of MBGNs or AIM alone. Furthermore, ROS levels were decreased by Ce-MBGNs alongside an upregulation of the expression of genes encoding for ROS-scavenging enzymes. Ce-MBGNs have proven their antioxidative potential. Mediated by the reduction of ROS, the undesired differentiation of BMSCs towards adipogenic lineage within BTE applications has been effectively suppressed. Ce-MBGNs target differentiation pathways in BMSCs precisely and therefore constitute an attractive biomaterial in the field of ion-based BTE.
CRIS-Team Scopus Importer:2025-02-17
Keywords: Adipogenesis; Bioactive glasses; Cerium; Human bone marrow derived mesenchymal stromal cells; Mesoporous bioactive glass nanoparticles; Reactive oxygen species

Cerium oxide nanoparticles loaded nanofibrous membranes promote bone regeneration for periodontal tissue engineering - Ren, Shuangshuang; Zhou, Yi; Zheng, Kai; Xu, Xuanwen; Yang, Jie; Wang, Xiaoyu; Miao, Leiying; Wei, Hui; Xu, Yan (Bioactive Materials, 2021)
Bone regeneration is a crucial part in the treatment of periodontal tissue regeneration, in which new attempts come out along with the development of nanomaterials. Herein, the effect of cerium oxide nanoparticles (CeO2 NPs) on the cell behavior and function of human periodontal ligament stem cells (hPDLSCs) was investigated. Results of CCK-8 and cell cycle tests demonstrated that CeO2 NPs not only had good biocompatibility, but also promoted cell proliferation. Furthermore, the levels of alkaline phosphatase activity, mineralized nodule formation and expressions of osteogenic genes and proteins demonstrated CeO2 NPs could promote osteogenesis differentiation of hPDLSCs. Then we chose electrospinning to fabricate fibrous membranes containing CeO2 NPs. We showed that the composite membranes improved mechanical properties as well as realized release of CeO2 NPs. We then applied the composite membranes to in vivo study in rat cranial defect models. Micro-CT and histopathological evaluations revealed that nanofibrous membranes with CeO2 NPs further accelerated new bone formation. Those exciting results demonstrated that CeO2 NPs and porous membrane contributed to osteogenic ability, and CeO2 NPs contained electrospun membrane may be a promising candidate material for periodontal bone regeneration.
CRIS-Team Scopus Importer:2021-06-18
Keywords: Bone regeneration; CeO; Electrospinning; Fibrous membrane; Periodontal ligament stem cells

Chapter 10: Bioactive Glass Particulate-incorporated Polymer Composites - Naseri, Shiva; Boccaccini, Aldo R.; Nazhat, Showan N. (Royal Society of Chemistry, 2017)
Bioactive glasses can potentially be used in combination with polymers in order to create a new complex of enhanced bioactivity, biocompatibility, and mechanical and degradation properties for biomedical applications. There are various processing routes to fabricate particulate bioactive glass fillers composites (dense or porous). Each fabrication route has its own advantages and disadvantages, and the best fabrication route is determined depending on the materials used and the desired final application. In this chapter, the main particulate bioactive glass-incorporated polymer composite fabrication techniques are presented, along with their associated pros and cons. Additionally, the properties of the various composites for tissue engineering and biomedical applications are discussed.
CRIS-Team Scopus Importer:2022-08-05

Chapter 16: Bioactive Glasses as Carriers of Therapeutic Ions and the Biological Implications - Hoppe, Alexander; Boccaccini, Aldo R. (Royal Society of Chemistry, 2017)
In the last few decades bioactive glasses (BGs) have been widely considered for bone tissue engineering applications due to their bioactivity and their osteogenic effects. The available scientific evidence suggests that ionic dissolution products (at a critical concentration) released during the degradation of the BG matrix induce osteogenic gene expression hence stimulating the bone regeneration process. Moreover, adding bioactive metallic ions (e.g. boron, copper, cobalt, lithium silver, zinc and strontium) to silicate as well as to phosphate and borate glasses has emerged as a promising route to develop novel BG formulations with specific therapeutic functionalities, including antibacterial, angiogenic, osteogenic and wound healing. The degradation behaviour of BGs can be tailored by adjusting the glass chemistry, making these biomaterials suitable carrier systems for controlled therapeutic ion release. This book chapter summarizes the fundamental aspects of the effect of ionic dissolution products released from BGs on osteogenesis and angiogenesis, also discussing novel BG compositions containing inorganic therapeutic agents. In vitro cellular as well as in vivo responses to specific therapeutic ions are discussed.
CRIS-Team Scopus Importer:2022-08-05

Chapter 5 - Mesoporous Bioactive Glass-Based Controlled Release Systems - Hum, Jasmin; Philippart, Anahi; Boccardi, Elena; Boccaccini, Aldo R. (Inorganic Controlled Release Technology Materials and Concepts for Advanced Drug Formulation, 2016)

Characterisation of a soft elastomer poly(glycerol sebacate) designed to match the mechanical properties of myocardial tissue - Boccaccini, Aldo R.; et al. (Biomaterials, 2008)
The myocardial tissue lacks significant intrinsic regenerative capability to replace the lost cells. Therefore, the heart is a major target of research within the field of tissue engineering, which aims to replace infarcted myocardium and enhance cardiac function. The primary objective of this work was to develop a biocompatible, degradable and superelastic heart patch from poly(glycerol sebacate) (PGS). PGS was synthesised at 110, 120 and 130 °C by polycondensation of glycerol and sebacic acid with a mole ratio of 1:1. The investigation was focused on the mechanical and biodegrading behaviours of the developed PGS. PGS materials synthesised at 110, 120 and 130 °C have Young's moduli of 0.056, 0.22 and 1.2 MPa, respectively, which satisfy the mechanical requirements on the materials applied for the heart patch and 3D myocardial tissue engineering construction. Degradation assessment in phosphate buffered saline and Knockout™ DMEM culture medium has demonstrated that the PGS has a wide range of degradability, from being degradable in a couple of weeks to being nearly inert. The matching of physical characteristics to those of the heart, the ability to fine tune degradation rates in biologically relevant media and initial data showing biocompatibility indicate that this material has promise for cardiac tissue engineering applications. © 2007 Elsevier Ltd. All rights reserved.
UnivIS-Import:2015-03-09:Pub.2008.tech.IW.LM.charac_7
Keywords: Biocompatibility; Degradation; Heart patch; Mechanical property; Myocardial tissue engineering; Poly(glycerol sebacate)

Characterisation of Bioglass based foams developed via replication of natural marine sponges - Boccardi, Elena; Philippart, Anahi; Juhasz-Bortuzzo, Judith Agnes; Novajra, G.; Vitale-Brovarone, C.; Boccaccini, Aldo R. (Advances in Applied Ceramics, 2015)
A comparative characterisation of Bioglass based scaffolds for bone tissue engineering applications developed via a replication technique of natural marine sponges as sacrificial template is presented, focusing on their architecture and mechanical properties. The use of these sponges presents several advantages, including the possibility of attaining higher mechanical properties than those scaffolds made by foam replica method (up to 4 MPa) due to a decrease in porosity (68-76%) without affecting the pore interconnectivity (higher than 99%). The obtained pore structure possesses not only pores with a diameter in the range 150-500 mu m, necessary to induce bone ingrowth, but also pores in the range of 0-200 mu m, which are requested for complete integration of the scaffold and for neovascularisation. In this way, it is possible to combine the main properties that a three-dimensional scaffold should have for bone regeneration: interconnected and high porosity, adequate mechanical properties and bioactivity.
Keywords: Natural marine sponges; Bioglass; Replication technique

Characterisation of carbon nanotube films deposited by electrophoretic deposition - Boccaccini, Aldo R.; et al. (Carbon, 2009)
UnivIS-Import:2015-03-09:Pub.2009.tech.IW.LM.charac_1

Characterisation of carbon nanotubes in the context of toxicity studies - Berhanu, Deborah; Dybowska, Agnieszka; Misra, Superb K.; Stanley, Chris J.; Ruenraroengsak, Pakatip; Boccaccini, Aldo R.; Tetley, Teresa D.; Luoma, Samuel N.; Plant, Jane A.; Valsami-Jones, Eugenia (Environmental Health, 2009)
Nanotechnology has the potential to revolutionise our futures, but has also prompted concerns about the possibility that nanomaterials may harm humans or the biosphere. The unique properties of nanoparticles, that give them novel size dependent functionalities, may also have the potential to cause harm. Discrepancies in existing human health and environmental studies have shown the importance of good quality, well-characterized reference nanomaterials for toxicological studies. Here we make a case for the importance of the detailed characterization of nanoparticles, using several methods, particularly to allow the recognition of impurities and the presence of chemically identical but structurally distinct phases. Methods to characterise fully, commercially available multi-wall carbon nanotubes at different scales, are presented. © 2009 Berhanu et al; licensee BioMed Central Ltd.
UnivIS-Import:2015-03-09:Pub.2009.tech.IW.LM.charac

Characterisation of porcine dermis scaffolds decellularised using a novel non-enzymatic method for biomedical applications - Greco, K. V.; Francis, L.; Somasundaram, M.; Greco, G.; English, Nicholas R.; Roether, Judith; Boccaccini, Aldo R.; Sibbons, P.; Ansari, T. (Journal of Biomaterials Applications, 2015)
Off-the-shelf availability of tissue-engineered skin constructs, tailored by different combinations of reagents to produce a highly preserved biological matrix is often the only means to help patients suffering skin damage. This study assessed the effect of five different decellularisation methods on porcine dermal scaffolds with regard to matrix composition, biomechanical strength, and cytotoxicity using an in vitro biocompatibility assay. Results demonstrated that four out of the five tested decellularisation protocols were efficient in producing acellular scaffolds. Nevertheless, decellularisation method using osmotic shock without enzymatic digestion showed to be efficient not only in removing cellular material and debris from dermal scaffolds but was also beneficial in the preservation of extracellular matrix components (glycosaminoglycans and collagen). Histological assessment revealed that the dermal architecture of coarse collagen bundles was preserved. Examinations by scanning electron microscopy and transmission electron microscopy showed that the arrangement and ultrastructure of collagen fibrils in the scaffolds were retained following non-enzymatic method of decellularisation and also after collagen crosslinking using genipin. Moreover, this decellularised scaffold was not only shown to be biologically compatible when co-cultured with bone marrow-derived mesenchymal stem cells and fibroblasts, but also stimulated the cells to release trophic factors essential for tissue regeneration.
Keywords: dermis; fibroblast; genipin; in vitro biocompatibility; mesenchymal stem cell; Scaffold

Characterisation of the bioactive behaviour of sol-gel hydroxyapatite-CaO and hydroxyapatite-CaO-bioactive glass composites - Hatzistavrou, E.; Chatzistavrou, X.; Papadopoulou, L.; Kantiranis, Nikolaos; Kontonasaki, E.; Boccaccini, Aldo R.; Paraskevopoulos, K. M. (Materials Science and Engineering C, 2010)
The fabrication and characterization of sol-gel derived hydroxyapatite-calcium oxide (HAp-CaO) material is investigated focusing on the effect of the addition of a bioactive glass on the material bioactive behaviour through the fabrication of a novel HAp-CaO (70 wt.%)-bioactive glass (30 wt.%) composite material. The bioactive behaviour of the materials was assessed by immersion studies in Simulated Body Fluid (SBF) and the alterations of the materials surfaces after soaking periods in SBF were characterized by Scanning Electron Microscopy (SEM) and Fourier Transform Infrared Spectroscopy (FTIR). A brittle and weakly crystalline carbonate hydroxyapatite (HCAp) layer was found to develop on the surface of all samples, few hours after immersion in SBF, confirming the high bioactivity of the material. Alterations of the morphology of the developed HCAp layer, which led to a more compact structure, were observed on the surface of composite samples after 7 days of immersion in SBF. The presence of the CaO phase seems to accelerate the formation of HCAp, while the bioactive glass affects both the morphology and cohesion of the developed layer. © 2010 Elsevier B.V. All rights reserved.
UnivIS-Import:2015-03-09:Pub.2010.tech.IW.LM.charac_3
Keywords: Bioactive glass; Bone regeneration; HAp-CaO; Simulated body fluid; Sol-gel method

Characterisation of vascularisation of scaffolds for tissue engineering - Arkudas, Andreas; Beier, Justus; Boccaccini, Aldo R.; Horch, Raymund E. (Materials Science and Technology, 2015)
Vascularisation of scaffolds is now recognised as a crucial requirement for the success of tissue engineering strategies. This review summarises the state-of-the-art in the techniques available for the in vivo assessment of vascularisation of scaffolds with focus on growth factor delivering scaffolds, microfabrication technologies and in vivo characterisation methods based on the arteriovenous loop model to create three dimensionally vascularised tissue replacements.
Keywords: Tissue engineering; AV loop; Cancer research; Regenerative medicine; Reviews

Characterising the sintering behaviour of pulverised fuel ash using heating stage microscopy - Boccaccini, Aldo R.; et al. (Materials Characterization, 2007)
Heating stage microscopy was used to investigate the sintering behaviour of pulverised fuel ash (PFA). The effect of chemical composition, heating rate, maximum temperature and metal inclusions on densification was studied. It was confirmed that dimensional changes of PFA powder compacts can be controlled by selecting appropriate conditions of sintering temperature and heating rate. It was also found that the sintering behaviour of PFA can be modified with the addition of metal inclusions. The results suggest that development of pores and microstructure of lightweight aggregates (LWA) manufactured from PFA can be controlled by changing the key sintering parameters such as temperature, time and heating rate. © 2006 Elsevier Inc. All rights reserved.
UnivIS-Import:2015-03-09:Pub.2007.tech.IW.LM.charac
Keywords: Coal ash; Densification; Heating microscopy; Metal inclusions; Sintering

Characterization of carbon nanotube (MWCNT) containing P(3HB)/bioactive glass composites for tissue engineering applications - Misra, Superb K.; Ohashi, F.; Valappil, Sabeel P.; Knowles, Jonathan C.; Roy, I.; Silva, S. Ravi P.; Salih, Vehid; Boccaccini, Aldo R. (Acta Biomaterialia, 2010)
Poly(3-hydroxybutyrate) (P(3HB)) composites with bioactive glass particles and multiwall carbon nanotubes (MWCNTs) were prepared and used to identify whether the electrical properties of MWCNTs can be used to detect the bioactivity of P(3HB)/bioactive glass composites. The presence of MWCNTs (2-7 wt.%) increased the surface roughness of the composites. The presence of MWCNTs in low quantity enhanced MG-63 osteoblast-like cell attachment and proliferation compared to composites with higher concentration of MWCNTs. Current-voltage measurements demonstrated that the electrical resistance of the composites containing bioactive glass particles decreased over a 45-day immersion period in SBF, whereas composites without bioactive glass showed no significant change over the same period. © 2009 Acta Materialia Inc.
UnivIS-Import:2015-03-09:Pub.2010.tech.IW.LM.charac
Keywords: Bioglass; Composites; Cytocompatibility; MWCNTs; Poly(3-hydroxybutyrate)

Characterization of electrophoretic chitosan coatings on stainless steel - Gebhardt, Franz; Seuß, Sigrid; Turhan, Can Metehan; Hornberger, Helga; Virtanen, Sannakaisa; Boccaccini, Aldo R. (Materials Letters, 2012)

Characterization of False Banana Fiber as a Potential Reinforcement Material for Geopolymer Composites - Addis, Lulseged Belay; Sendekie, Zenamarkos Bantie; Habtu, Nigus Gabbiye; Schubert, Dirk W.; Roether, Judith; Boccaccini, Aldo R. (Green Energy and Technology, 2023)
There is renewed interest in the use of plant-derived fibers as reinforcement material in the manufacture of composites. Replacing synthetic fiber with natural fiber has several benefits. Availability, biodegradability, lightweight, reduction of carbon footprint, and less abrasiveness in tool wear during processing are among the common benefits over synthetic fiber counterparts. The objective of this study is to investigate the physical, mechanical, thermal, and chemical properties of false banana fiber, obtained from false banana plants. The results show that the fiber has a relatively low moisture content, demonstrating that the false banana fiber has good physical properties as the moisture content of the fiber determines the dimensional stability of the produced composites. The mean diameter and true density of the fiber were found to be 173 μm and 1.483 g/cm3, respectively. A single fiber tensile test was carried out to determine the mechanical strength of the fiber. Its strength varied between 125 and 784 MPa. Based on the thermal stability test, the initial degradation of the fiber starts at 263 °C while its maximum degradation is observed at 364 °C. From the results of the chemical analysis, the fiber contains about 58.16% cellulose, 23.64% hemicellulose, and 11.12% lignin as the main components, and a small amount of extractives and ash, 4.04%, and 3.03%, respectively. Based on the overall analysis of the test results, the false banana fiber can be confirmed as one of the potential reinforcement source materials that can be used for the production of polymer composites for various applications.
CRIS-Team Scopus Importer:2023-09-08
Keywords: Chemical analysis; False banana fiber; Mechanical properties; Physical properties; Thermal properties

Characterization of Nanostructured Ceramic and Cermet Coatings Deposited by Plasma Spraying - Sanchez, Enrique; Bannier, Emilie; Vicent, Monica; Moreno, Arnaldo; Salvador, Maria Dolores; Bonache, Victoria; Klyatskina, Elizabeta; Boccaccini, Aldo R. (International Journal of Applied Ceramic Technology, 2010)
UnivIS-Import:2015-03-09:Pub.2010.tech.IW.LM.charac_2

Characterization of polyetheretherketone particle suspensions for electrophoretic deposition - Clavijo, Silvia; Membrives, Francisco; Boccaccini, Aldo R.; Santillan, Maria J. (Journal of Applied Polymer Science, 2014)
Suspensions of polyetheretherketone (PEEK) using mixture of ethanol and isopropanol as solvent were prepared to carry out PEEK electrophoretic deposition (EPD). The rheological behavior and suspension structure of PEEK particles dispersed in co-solvents were investigated over a range of pH values (1-10) and shear rates (γ = 10-3 × 10 s ). These PEEK suspensions generally exhibited a pseudoplastic flow behavior, indicating the occurrence of particle aggregation in the liquid medium. The maximum solids fraction (φ) showed an estimated value of φ = 2.9 wt %. Using a suspension with 3 wt % PEEK concentration, PEEK coatings on stainless steel substrates were obtained by EPD at constant voltage condition. The influence of the electrolyte conductivity on PEEK EPD from ethanol-isopropanol suspensions was studied. Experimental results showed that high-conductivity ethanol-based suspensions yield non-uniform deposits, while low-conductivity suspensions resulted in uniform coatings. The difference in the deposition behavior is due to the different pH of the suspensions and the relationship of pH with suspension conductivity. pH = 8 was the optimal value for this system in terms of deposition results. The surfaces of EPD PEEK coatings were homogenous and a qualitatively good adhesion between the PEEK deposits and the substrate was confirmed. © 2014 Wiley Periodicals, Inc.
Keywords: biomaterials; biomedical applications; coatings

Characterization of TiO2 nanoparticle suspensions for electrophoretic deposition - Santillan, Maria Jose; Membrives, Francisco; Quaranta, Nancy; Boccaccini, Aldo R. (Journal of Nanoparticle Research, 2008)
The rheology of suspensions is critically important for the successful achievement of defect-free TiO2 deposits by electrophoretic deposition (EPD). The rheological behaviour of TiO2 nanoparticle suspensions in acetylacetone with and without iodine was investigated over a broad solid-concentration range (0.3-2.5 wt.%) and at different shear rates (γ = 10-250 s-1). The influence of these parameters on the quality of TiO2 films obtained by EPD on stainless steel substrates was assessed. The pure solvent and the 1 wt.% TiO2 nanoparticles suspension without iodine exhibited shear-thickening flow behaviour. For other concentrations, the suspensions showed shear-thinning behaviour followed by an apparent shear-thickening effect at a critical shear rate (100 s-1). For the suspension with 1 wt.% TiO2 containing iodine, a shear-thickening flow behaviour was observed over the whole shear rate range investigated. The maximum solids fraction (φm) was experimentally determined from a linear relationship between solid concentration and viscosity. The estimated value was φm = 7.94 wt.% for this system. Using a suspension with 1 wt.% concentration, good-quality TiO 2 deposits on stainless steel planar substrates were obtained by EPD at constant voltage condition. The influence of pH on suspension stability was determined in the range pH = 1-9, being pH ≈ 5 the optimal value for this system in terms of EPD results. © 2007 Springer Science+Business Media B.V.
UnivIS-Import:2015-03-09:Pub.2008.tech.IW.LM.charac
Keywords: Colloids; Electrophoretic deposition; Rheology; Suspensions; Titanium dioxide

Characterization of two different alginate-based bioinks and the influence of melanoma growth within - Schipka, Raphael; Heltmann-Meyer, Stefanie; Schneidereit, Dominik; Friedrich, Oliver; Röder, Jonas; Boccaccini, Aldo R.; Schrüfer, Stefan; Schubert, Dirk W.; Horch, Raymund E.; Boßerhoff, Anja Katrin; Arkudas, Andreas; Kengelbach-Weigand, Annika; et al. (Scientific Reports, 2024)
Extrusion-based bioprinting is an established method in biofabrication. Suitable bioinks have fundamentally different compositions and characteristics, which should be examined, in order to find a perfect model system. Here, we investigate the effect of two alginate-based, yet unalike 3D-printed bioinks, pre-crosslinked alginate-dialdehyde gelatin (ADA-GEL) and a mixture of alginate, hyaluronic acid, and gelatin (Alg/HA/Gel), on the melanoma cell line Mel Im and vice versa in terms of stiffness, shrinkage, cellular behavior and colony formation over 15 days. Rheological stiffness measurements revealed two soft gels with similar storage moduli. The cells did not have a significant impact on the overall stiffness, whereas ADA-GEL (2.5/2.5%) was significantly stiffer than Alg/HA/Gel (0.5/0.1/3%). Regarding the shrinkage of printed constructs, cells had a significant influence, especially in ADA-GEL, which has covalent bonds between the oxidized alginate and gelatin. Multi-photon microscopy exhibited proliferation, cell spreading and migration in ADA-GEL with cell–cell and cell–matrix interaction, dissimilarly to Alg/HA/Gel, in which cells formed spherical, encapsulated colonies. Scanning electron microscopy and histology showed degradation and multi-layered growth on ADA-GEL and fewer examples of escaped cells on Alg/HA/Gel. Both gels serve as proliferation bioink for melanoma with more necrosis in deeper Alg/HA/Gel colonies and differences in spreading and matrix interaction. These findings show the importance of proper characterization of the bioinks for different applications.
CRIS-Team Scopus Importer:2024-06-14
Keywords: 3D-printing; Alginate; Hydrogel; Melanoma; Stiffness

Characterizing the degradation behavior of bioceramic scaffolds - Goudouri, Ourania Menti; Balasubramanian, Preethi; Boccaccini, Aldo R. (Elsevier Inc., 2016)
The use of bioceramic scaffolds for hard tissue repair, augmentation, and substitution is continuously increasing in many dental and medical applications. It is well established that the in vivo biodegradation and bioresorption of ceramic scaffolds at rates appropriate to tissue regeneration play a vital role in enabling new tissue formation. Furthermore, the various ionic by-products of biodegradation of scaffolding materials result in the enrichment of the microenvironment, which can affect, positively or negatively, the proliferation and activity of cells. Therefore, the factors affecting degradation or the extent of dissolution of the scaffolding materials are important. The aim of this chapter is to discuss the processes of biodegradation or bioresorption of bioceramic scaffolds in terms of the physical, chemical, and biocompatibility that occur when in contact with simulated body fluids, cells, or living tissue, focusing on the applied characterization techniques.
CRIS-Team Scopus Importer:2022-08-05
Keywords: Bioactive Glasses; Bioceramics; In vitro/In vivo dissolution; Ion release; PH Changes; Weight Loss

Chitosan/bioactive glass coatings as a protective layer against corrosion of nanocrystalline titanium under simulated inflammation - Sotniczuk, Agata; Heise, Svenja; Topolski, Krzysztof; Garbacz, Halina; Boccaccini, Aldo R. (Materials Letters, 2020)
Hydrogen peroxide (H2O2), which is produced during inflammation directly after the insertion of an implant, accelerates the corrosion process of Ti-based materials such as nanocrystalline bulk titanium. For this reason, there is a need to provide additional corrosion protection in the initial period following implantation. Coatings based on chitosan/bioactive glass were obtained by electrophoretic deposition (EPD) on nanocrystalline Ti. Results indicated that homogeneous, crack-free composite chitosan/bioactive glass EPD coatings effectively increased the resistance of nanocrystalline titanium to dissolution induced by H2O2.
CRIS-Team Scopus Importer:2020-01-21
Keywords: Biomaterials; Corrosion; Electrodeposition; Metals and alloys

Chitosan/hydroxyapatite composite bone tissue engineering scaffolds with dual and decoupled therapeutic ion delivery: copper and strontium - Gritsch, Lukas; Maqbool, Muhammad; Mouriño, Viviana; Ciraldo, Francesca; Cresswell, Mark; Jackson, Philip R.; Lovell, Christopher; Boccaccini, Aldo R. (Journal of Materials Chemistry B, 2019)
Therapeutic metal ions are a family of metal ions characterized by specific biological properties that could be exploited in bone tissue engineering, avoiding the use of expensive and potentially problematic growth factors and other sensitive biomolecules. In this work, we report the successful preparation and characterization of two material platforms containing therapeutic ions: a copper(ii)-chitosan derivative and a strontium-substituted hydroxyapatite. These biomaterials showed ideal ion release profiles, offering burst release of an antibacterial agent together with a more sustained release of strontium in order to achieve long-term osteogenesis. We combined copper(ii)-chitosan and strontium-hydroxyapatite into freeze-dried composite scaffolds. These scaffolds were characterized in terms of morphology, mechanical properties and bioactivity, defined here as the ability to trigger the deposition of novel calcium phosphate in contact with biological fluids. In addition, a preliminary biological characterization using cell line osteoblasts was performed. Our results highlighted that the combination of chitosan and hydroxyapatite in conjunction with copper and strontium has great potential in the design of novel scaffolds. Chitosan/HA composites can be an ideal technology for the development of tissue engineering scaffolds that deliver a complex arrays of therapeutic ions in both components of the composite, leading to tailored biological effects, from antibacterial activity, to osteogenesis and angiogenesis.
CRIS-Team Scopus Importer:2019-10-22

Chitosan membranes containing micro or nano-size bioactive glass particles: evolution of biomineralization followed by in situ dynamic mechanical analysis - Caridade, Sofia G.; Merino, Esther G.; Alves, Natalia M.; Bermudez, Veronica De Zea; Boccaccini, Aldo R.; Mano, Joao F. (Journal of the Mechanical Behavior of Biomedical Materials, 2013)
A new family of biodegradable polymer/bioactive glass (BG) composite materials has emerged based on the availability of nano-sized bioactive particles. Such novel biocomposites can have enhanced performance, in terms of mechanical properties and bioactivity, and they can be designed to be used in bone regeneration approaches.In this work, membranes of chitosan (CTS) and chitosan with bioactive glass (BG) both micron and nano sized particles (CTS/μBG, CTS/nBG, respectively) were prepared by solvent casting. Microstructural and mechanical properties were evaluated in order to compare the effects of the incorporation of micro (μBG) and nano (nBG) particles in the chitosan matrix. In vitro bioactivity tests were performed to characterize the apatite layer that is formed on the surface of the material after being immersed in simulated body fluid (SBF). The biomineralization process on the biomaterials was also followed using non-conventional dynamic mechanical analysis (DMA), both online and offline. In such DMA experiments, the change in the storage modulus, E', and the loss factor, tan δ, were measured as a function of the immersion time in SBF. The results demonstrated that CTS/nBG membranes possess enhanced mechanical properties and higher bioactivity in comparison with the CTS/μBG membranes. Such results suggest the potential of nBG for the development of bioactive composites for bone regeneration applications. © 2012 Elsevier Ltd.
UnivIS-Import:2015-03-09:Pub.2013.tech.IW.LM.chitos
Keywords: Bioactive glass; Bioactivity; Bone regeneration; Dynamic mechanical analysis; Nanocomposites

Chondrogenesis of human bone marrow mesenchymal stromal cells in highly porous alginate-foams supplemented with chondroitin sulfate - Huang, Zhao; Nooeaid, Patcharakamon; Kohl, Benjamin; Roether, Judith; Schubert, Dirk W.; Meier, Carola; Boccaccini, Aldo R.; Godkin, Owen; Ertel, Wolfgang; Arens, Stephan; Schulze-Tanzil, Gundula (Materials Science and Engineering C, 2015)
To overcome the limited intrinsic cartilage repair, autologous chondrocyte or bone-marrow-derived mesenchymal stromal cell (BM-MSC) was implanted into cartilage defects. For this purpose suitable biocompatible scaffolds are needed to provide cell retention, chondrogenesis and initial mechanical stability. The present study should indicate whether a recently developed highly porous alginate (Alg) foam scaffold supplemented with chondroitin sulfate (CS) allows the attachment, survival and chondrogenesis of BM-MSCs and articular chondrocytes. The foams were prepared using a freeze-drying method; some of them were supplemented with CS and subsequently characterized for porosity, biodegradation and mechanical profile. BM-MSCs were cultured for 1-2 weeks on the scaffold either under chondrogenic or maintenance conditions. Cell vitality assays, histology, glycosaminoglycan (sGAG) assay, and type II and I collagen immunolabelings were performed to monitor cell growth and extracellular matrix (ECM) synthesis in the scaffolds. Scaffolds had a high porosity similar to 93-95% with a mean pore sizes of 237 +/- 48 mu m (Alg) and 197 +/- 61 mu m (Alg/CS). Incorporation of CS increased mechanical strength of the foams providing gradually CS release over 7 days. Most of the cells survived in the scaffolds. BM-MSCs and articular chondrocytes formed rounded clusters within the scaffold pores. The BM-MSCs, irrespective of whether cultured under non/chondrogenic conditions and chondrocytes produced an ECM containing sGAGs, and types II and I collagen. Total collagen and sGAG contents were higher in differentiated BM-MSC cultures supplemented with CS than in CS-free foams after 14 days. The cell cluster formation induced by the scaffolds might stimulate chondrogenesis via initial intense cell-cell contacts. (C) 2015 Elsevier B.V. All rights reserved.
Keywords: Chondrogenesis; Alginate-foam scaffolds; Chondrocytes; Mesenchymal stromal cells; Chondroitin sulfate

Cobalt-Releasing 1393 Bioactive Glass-Derived Scaffolds for Bone Tissue Engineering Applications - Hoppe, Alexander; Jokic, Bojan; Janackovic, Djordje; Fey, Tobias; Greil, Peter; Romeis, Stefan; Schmidt, Jochen; Peukert, Wolfgang; Lao, Jonathan; Jallot, Edouard; Boccaccini, Aldo R. (ACS Applied Materials and Interfaces, 2014)
Loading biomaterials with angiogenic therapeutics has emerged as a promising approach for developing superior biomaterials for engineering bone constructs. In this context, cobalt-releasing materials are of interest as Co is a known angiogenic agent. In this study, we report on cobalt-releasing three-dimensional (3D) scaffolds based on a silicate bioactive glass. Novel melt-derived "1393" glass (53 wt % SiO2, 6 wt % Na2O, 12 wt % K2O, wt % MgO, 20 wt % CaO, and 4 wt % P2O5) with CoO substituted for CaO was fabricated and was used to produce a 3D porous scaffold by the foam replica technique. Glass structural and thermal properties as well as scaffold macrostructure, compressive strength, acellular bioactivity, and Co release in simulated body fluid (SBF) were investigated. In particular, detailed insights into the physicochemical reactions occurring at the scaffold-fluid interface were derived from advanced micro-particle-induced X-ray emission/Rutherford backscattering spectrometry analysis. CoO is shown to act in a concentration-dependent manner as both a network former and a network modifier. At a concentration of 5 wt % CoO, the glass transition point (T-g) of the glass was reduced because of the replacement of stronger Si-O bonds with Co-O bonds in the glass network. Compressive strengths of >2 MPa were measured for Co-containing 1393-derived scaffolds, which are comparable to values of human spongy bone. SBF studies showed that all glass scaffolds form a calcium phosphate (CaP) layer, and for 1393-1Co and 1393-5Co, CaP layers with incorporated traces of Co were observed. The highest Co concentrations of similar to 12 ppm were released in SBF after reaction for 21 days, which are known to be within therapeutic ranges reported for Co2+ ions.
Keywords: cobalt; hypoxia; bioglass; bioactive; scaffold; bone tissue engineering; angiogenesis

Co-culture of BMSCs and HUVECs with simvastatin-loaded gelatin nanosphere/chitosan coating on Mg alloy for osteogenic differentiation and vasculogenesis - Qi, Hongfei; Wang, Kun; Li, Meng; Zhang, Yanni; Dong, Kai; Heise, Svenja; Boccaccini, Aldo R.; Lu, Tingli (International Journal of Biological Macromolecules, 2021)
Mg alloys are increasingly being investigated as a versatile and economical alternative for developing bone repair implants because of their high mechanical strength, wide availability, adjustable structure and properties. In this study, magnesium alloy WE43 is coated on both sides with gelatin nanosphere/chitosan (GNs/CTS), a coating enhanced by incorporating simvastatin (SIM). SIM-loaded GNs/CTS coated magnesium alloy can promote the osteogenic differentiation of bone mesenchymal stem cells (BMSCs). BMSCs and human umbilical vein endothelial cells (HUVECs) are co-cultured through transwell systems. The release of SIM from the coating is found to increase the secretion of chemokine and angiogenic factors from BMSCs, which promote the migration and tube formation of HUVECs, respectively. Bone morphogenetic protein secreted by HUVECs is seen to increase by the release of SIM from the coating, promoting the osteogenic differentiation of BMSCs. The secretion of chemokines from HUVECs promote the migration of BMSCs. The coated magnesium alloy substrate loaded with SIM is found to regulate the osteogenic differentiation of BMSCs. The study of the paracrine interaction between BMSCs and HUVECs proves that the applied coating promotes both osteogenic differentiation and vascularization, thus demonstrating a new approach for the design of bone repair materials based on magnesium alloys.
CRIS-Team WoS Importer:2022-01-14

Co-delivery of 5-fluorouracil and oxali-palladium via β-lactoglobulin nano-capsules coated with Low Methoxyl Pectin for colon cancer therapy - Leilabadi-Asl, Amineh; Ghalandari, Behafarid; Divsalar, Adeleh; Karizak, Ashkan Zare; Haertlé, Thomas; Ding, Xianting; Saboury, Ali Akbar; Ghorbani, Farnaz (Journal of Drug Delivery Science and Technology, 2023)
Chemotherapy is associated with serious side effects in terms of its high toxicity. Optimizing nanoscale drug delivery systems offers a way to overcome these side effects in cancer treatment. This research studies the synthesis and optimization of β-lactoglobulin (β-LG) nanocapsules coated with Low Methoxyl Pectin (LMP) for the simultaneous delivery of two major drugs, 5-fluorouracil (5-FU) and Oxali-palladium, used for colon cancer chemotherapy. The current research investigates the co-delivery system's physical characteristics, drug loading, and in vitro drug release, as well as its toxicity against the colon cancer cell line. Our findings show that the present co-delivery system uniformly forms, especially at pH 4.5, and has a size <120 nm, this being well optimized for colon cancer cell pores. Moreover, this co-delivery system demonstrates drug encapsulation efficiency of more than 60% for both drugs. Furthermore, it has shown stability and resistance to low-pH acidic conditions. In contrast, it shows the sensitivity to alkaline conditions, which determines that the co-delivery system is optimized for the colon cancer environment. The in vitro drug release results confirm these findings as the highest release rate is associated with the simulated colon cancer conditions. Hence, the present co-delivery system shows higher cytotoxicity toward colon cancer cell lines when compared to free drugs. An in-depth optimization of the co-delivery system of 5-FU and Oxali-palladium using β-LG and LMP is provided, which promotes the development of a protein-based co-delivery system at the nanoscale. Finally, it can be concluded that the presented co-delivery system is very promising to be used in oral drug delivery for colon cancer treatment.
CRIS-Team Scopus Importer:2023-10-13
Keywords: 5-Fluorouracil; Colorectal cancer; Nano-capsule; Oxali-palladium; β-Lactoglobulin

Co-deposition of CuO and Mn1.5Co1.5O4 powders on Crofer22APU by electrophoretic method: Structural, compositional modifications and corrosion properties - Molin, Sebastian; Sabato, A. G.; Javed, Hassan; Cempura, Grzegorz; Boccaccini, Aldo R.; Smeacetto, F. (Materials Letters, 2018)
Co-deposition of CuO and Mn1.5Co1.5O4 by single step electrophoretic deposition is used to produce ∼15 µm coatings on Crofer22APU steel, which finds use as interconnect for high temperature solid oxide cells. Sintering of the green coatings in reducing and then oxidizing conditions led to formation of a mixed (Cu,Mn,Co)3O4 spinel. By the incorporation of Cu, the density of the coatings improved. Scanning and transmission electron microscopy observations, supplemented with energy dispersive spectroscopy, confirmed dissolution of Cu in the spinel phase. For the un-doped Mn1.5Co1.5O4 both the tetragonal and cubic phases are detected at room temperature by X-ray diffractometry, whereas the addition of Cu seems to stabilize the cubic phase. Initial (∼1000 h) high temperature corrosion evaluation at 800 °C in air showed promising properties of the mixed spinel coating.
CRIS-Team Scopus Importer:2022-08-05
Keywords: Ceramics; Corrosion; Deposition; Sintering

Co-doping of iron and copper ions in nanosized bioactive glass by reactive laser fragmentation in liquids - Li, Yaya; Ramesh, Vaijayanthi; Bider, Faina; Bradshaw, Nathan; Rehbock, Christoph; Boccaccini, Aldo R.; Barcikowski, Stephan (Journal of Biomedical Materials Research Part A, 2022)
Bioactive glass (BG) is a frequently used biomaterial applicable in bone tissue engineering and known to be particularly effective when applied in nanoscopic dimensions. In this work, we employed the scalable reactive laser fragmentation in liquids method to produce nanosized 45S5 BG in the presence of light-absorbing Fe and Cu ions. Here, the function of the ions was twofold: (i) increasing the light absorption and thus causing a significant increase in laser fragmentation efficiency by a factor of 100 and (ii) doping the BG with bioactive metal ions up to 4 wt%. Our findings reveal an effective downsizing of the BG from micrometer-sized educts into nanoparticles having average diameters of <50 nm. This goes along with successful element-specific incorporation of the metal ions into the BG, inducing co-doping of Fe and Cu ions as verified by energy-dispersive X-ray spectroscopy (EDX). In this context, the overall amorphous structure is retained, as evidenced by X-ray powder diffraction (XRD). We further demonstrate that the level of doping for both elements can be adjusted by changing the BG/ion concentration ratio during laser fragmentation. Consecutive ion release experiments using inductively-coupled plasma mass spectrometry (ICP-MS) were conducted to assess the potential bioactivity of the doped nanoscopic BG samples, and cell culture experiments using MG-63 osteoblast-like cells demonstrated their cytocompatibility. The elegant method of in situ co-doping of Fe and Cu ions during BG nanosizing may provide functionality-advanced biomaterials for future studies on angiogenesis or bone regeneration, particularly as the level of doping may be adjusted by ion concentrations and ion type in solution.
CRIS-Team Scopus Importer:2022-04-29
Keywords: bioactive ion doped bioglass; biocompatibility; biomaterials; bone tissue; engineering; laser doping

Cold hydrostatic sintering of 45S5 bioactive glass - Nawaz, Qaisar; Pantulap, Usanee; Hurle, Katrin; Luo, Nan; Grasso, Salvatore; Boccaccini, Aldo R. (European Journal of Materials, 2023)
Fully amorphous 45S5 bioactive glass pellets were successfully consolidated at room temperature using cold hydrostatic sintering (CHS) and their acellular bioactivity was determined by immersion test in simulated body fluid (SBF). Crystalline 45S5 BG samples prepared using conventional sintering (TS) at 1050 °C were also tested. Preliminary results indicated the formation of hydroxyapatite (HAP) on the surfaces of both samples after immersion in SBF, which was confirmed using SEM, FTIR, and XRD analyses. The amount of hydroxyapatite increases by increasing the SBF immersion time. Results revealed that the amount of HAP crystalline phase was similar in both samples after 14 days of incubation in SBF (i.e., 23% in TS and 25% in CHS samples). The pellets prepared by TS resulted in a relative density of 95.6% and a hardness of about 3.5 GPa. On the other hand, CHS samples had a hardness of 1.2 GPa and a relative density of 75.1%, indicating the presence of a porous structure that can be beneficial for the interaction of the material with proteins and cells (both in vitro and in vivo).
CRIS-Team Scopus Importer:2024-12-16
Keywords: Bioactive glasses; bioactivity; cold hydrostatic sintering; densification

Collagen as coating material for 45S5 bioactive glass-based scaffolds for bone tissue engineering - Hum, Jasmin; Boccaccini, Aldo R. (International Journal of Molecular Sciences, 2018)
Keywords: Bone tissue engineering; Collagen; Bioactive glass; Scaffolds; Surface functionalization

Collagen release kinetics of surface functionalized 4555 Bioglass (R)-based porous scaffolds - Boccaccini, Aldo R.; et al. (Journal of Biomedical Materials Research Part A, 2008)
UnivIS-Import:2015-03-09:Pub.2008.tech.IW.LM.collag

Collagen scaffolds functionalised with copper-eluting bioactive glass reduce infection and enhance osteogenesis and angiogenesis both in vitro and in vivo - Ryan, Emily J.; Ryan, Alan J.; Gonzalez-Vazquez, Arlyng; Philippart, Anahi; Ciraldo, Francesca; Hobbs, Christopher; Nicolosi, Valeria; Boccaccini, Aldo R.; Kearney, Cathal J.; O'Brien, Fergal J. (Biomaterials, 2019)
The bone infection osteomyelitis (typically by Staphylococcus aureus) usually requires a multistep procedure of surgical debridement, long-term systemic high-dose antibiotics, and for larger defects bone grafting. This, combined with the alarming rise in antibiotic resistance, necessitates development of alternative approaches. Herein, we describe a one-step treatment for osteomyelitis that combines local, controlled release of non-antibiotic antibacterials with a regenerative collagen-based scaffold. To maximise efficacy, we utilised bioactive glass, an established osteoconductive material with immense capacity for bone repair, as a delivery platform for copper ions (proven antibacterial, angiogenic, and osteogenic properties). Multifunctional collagen-copper doped bioactive glass scaffolds (CuBG-CS) were fabricated with favourable microarchitectural and mechanical properties (up to 1.9-fold increase in compressive modulus over CS) within the ideal range for bone tissue engineering. Scaffolds demonstrated antibacterial activity against Staphylococcus aureus (up to 66% inhibition) whilst also enhancing osteogenesis (up to 3.6-fold increase in calcium deposition) and angiogenesis in vitro. Most significantly, when assessed in a chick embryo in vivo model, CuBG-CS not only demonstrated bio-compatibility, but also a significant angiogenic and osteogenic response, consistent with in vitro studies. Collectively, these results indicate that the CuBG-CS developed here show potential as a one-step osteomyelitis treatment: reducing infection, whilst enhancing bone healing.
CRIS-Team WoS Importer:2019-03-06

Collagen/silica nanocomposites and hybrids for bone tissue engineering - Sarker, Bapi; Lyer, Stefan; Arkudas, Andreas; Boccaccini, Aldo R. (Nanotechnology Reviews, 2013)
UnivIS-Import:2015-04-14:Pub.2013.tech.IW.LM.collag

Combination of electrophoretic deposition and microwave-ignited combustion synthesis for the preparation of ceramic coated intermetallic-based materials - Rosa, Roberto; Veronesi, Paolo; Michelazzi, Marco; Leonelli, Cristina; Boccaccini, Aldo R. (Surface & Coatings Technology, 2012)
Electrophoretic deposition (EPD) was used to deposit sub-micrometric ZrO 2 particles on metallic powder compacts belonging to the systems Ni+Al and Ti+Al, which were used as deposition electrodes in the EPD cell. After EPD, combustion synthesis (CS) of such reactive electrodes was ignited in a microwave single-mode applicator, operating at a frequency of 2.45GHz, in order to obtain in a single step the synthesis of the desired intermetallic phase (substrate) and the sintering of the previously deposited ceramic particles (or coating). Experimental results demonstrate that the excess heat released during the formation of nickel and titanium aluminides by CS can be exploited not only to self-sustain and self-propagate the reaction front along the substrate, but also to rapidly sinter the coating obtained by EPD. The innovative procedure here proposed is a promising strategy in order to obtain, in a single step, high temperature intermetallic-based materials, protected by well adhered ceramic coatings. © 2012 Elsevier B.V.
UnivIS-Import:2015-03-09:Pub.2012.tech.IW.LM.combin
Keywords: Coatings; Combustion synthesis; Electrophoretic deposition; Intermetallics; Microwave processing

Combination of selective etching and impregnation toward hollow mesoporous bioactive glass nanoparticles - Mutlu, Nurshen; Beltran, Ana Maria; Nawaz, Qaisar; Michalek, Martin; Boccaccini, Aldo R.; Zheng, Kai (Nanomaterials, 2021)
In this study, binary SiO2-CaO hollow mesoporous bioactive glass nanoparticles (HMBGNs) are prepared by combing selective etching and impregnation strategies. Spherical silica particles (SiO2 NPs) are used as hard cores to assemble cetyltrimethylammonium bromide (CTAB)/silica shells, which are later removed by selective etching to generate a hollow structure. After the removal of CTAB by calcination, the mesoporous shell of particles is formed. Calcium (Ca) is incorporated into the particles using impregnation by soaking the etched SiO2 NPs in calcium nitrate aqueous solution. The amount of incorporated Ca is tailorable by controlling the ratio of SiO2 NPs:calcium nitrate in the soaking solution. The produced HMBGNs are bioactive, as indicated by the rapid formation of hydroxyapatite on their surfaces after immersion in simulated body fluid. In a direct culture with MC3T3-E1 cells, HMBGNs were shown to exhibit concentration-dependent cytotoxicity and can stimulate osteogenic differentiation of MC3T3-E1 cells at concentrations of 1, 0.5, and 0.25 mg/mL. Our results indicate that the combination of selective etching and impregnation is a feasible approach to produce hierarchical HMBGNs. The produced hollow particles have potential in drug delivery and bone tissue regeneration applications, and should be further investigated in detailed in vitro and in vivo studies.
CRIS-Team Scopus Importer:2021-07-30
Keywords: Alkaline etching; Bioactive glasses; Bone regeneration; Hollow mesoporous structure; Impregnation

Combining bioresorbable polyesters and bioactive glasses: Orthopedic applications of composite implants and bone tissue engineering scaffolds - Gritsch, Lukas; Perrin, Eloïse; Chenal, Jean Marc; Fredholm, Yann; Maçon, Anthony LB; Chevalier, Jérôme; Boccaccini, Aldo R. (Applied Materials Today, 2021)
This overview showcases the current state of the art in the fabrication, properties and applications of bioactive glass-polyester composites for dentistry, craniomaxillofacial surgery, orthopedics and bone tissue engineering. The combination of these materials is a successful strategy to simultaneously modulate and optimize the degradation rate, mechanical properties, cell response and osteostimulation of bone substitutes. Two major approaches can be identified: bone regeneration or bone repair. The first is performed using porous scaffolding materials, the second one by dense molded implants. For both strategies, the synthesis, processing and characterization of materials are presented based on a comprehensive review of the available literature. Relevant recent in vitro and in vivo studies are also covered. Current and potential future applications of this interesting family of biocomposites are discussed. The literature search revealed a considerable body of work investigating the biological performance of these composites, evidencing the interest on the topic. In particular, the use of polyester/BG composites is well-studied in terms of material fabrication, as well as characterization of physicochemical and in vitro biological properties. On the other hand, there is much less evidence of translational research efforts. It is apparent that future research will have to focus on the collection of more in vivo and clinical data to broaden the knowledge of the time dependent performance of these materials in realistic conditions.
CRIS-Team Scopus Importer:2021-01-15
Keywords: Bioactive glasses; Bioresorbable polyesters; Composites; Orthopedics; Scaffolds

Combining Collagen and Bioactive Glasses for Bone Tissue Engineering: A Review - Sarker, Bapi; Hum, Jasmin; Nazhat, Showan N.; Boccaccini, Aldo R. (Advanced Healthcare Materials, 2014)
Collagen (COL), the most abundant protein in mammals, offers a wide range of attractive properties for biomedical applications which are the result of its biocompatibility and high affinity to water. However, due to the relative low mechanical properties of COL its applications are still limited. To tackle this disadvantage of COL, especially in the field of bone tissue engineering, COL can be combined with bioactive inorganic materials in a variety of composite systems. One of such systems is the collagen-bioactive glass (COL-BG) composite family, which is the theme of this Review. BG fillers can increase compressive strength and stiffness of COL-based structures. This article reviews the relevant literature published in the last 15 years discussing the fabrication of a variety of COL-BG composites. In vitro cell studies have demonstrated the osteogenic, odontogenic, and angiogenic potential of these composite systems, which has been confirmed by stimulating specific biochemical indicators of relevant cells. Bony integration and connective tissue vessel formation have also been studied by implantation of the composites in vivo. Areas of future research in the field of COL-BG systems, based on current challenges, and gaps in knowledge are highlighted.

Combining Mesoporous Bioactive Glass Nanoparticles (MBGNs) with Essential Oils to Tackle Bacterial Infection and Oxidative Stress for Bone Regeneration Applications - Damian-Buda, Andrada-Ioana; Ünalan, Irem; Boccaccini, Aldo R. (ACS Biomaterials Science and Engineering, 2024)
Bacterial infectious diseases remain one of the significant challenges in the field of bone regeneration applications. Despite the development of new antibiotics, their improper administration has led to the development of multiresistant bacterial strains. In this study, we proposed a novel approach to tackle this problem by loading clove oil (CLV), a natural antibacterial compound, into amino-functionalized mesoporous bioactive glass nanoparticles (MBGNs). The scanning electron microscopy images (SEM) revealed that amino-functionalization and CLV loading did not affect the shape and size of the MBGNs. The successful grafting of the amino groups on the MBGNs’ surface and the presence of CLV in the material were confirmed by attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy and zeta potential measurements. The increased CLV concentration led to a higher loading capacity, encapsulation efficiency, and antioxidant activity. The in vitro CLV release profile exhibited an initial burst release, followed by a controlled release over 14 days. The loading of CLV into MBGNs led to a stronger antibacterial effect against E. coli and S. aureus, while MG-63 osteoblast-like cell viability was enhanced with no morphological changes compared to the control group. In conclusion, the CLV-MBGNs nanocarriers showed promising properties in vitro as novel drug delivery systems, exploiting essential oils for treating bone infections and oxidative stress.
CRIS-Team Scopus Importer:2024-11-01
Keywords: antibacterial activity; antioxidant activity; clove oil; controlled drug delivery system; mesoporous bioactive glass nanoparticles

Comparative Study of the Antimicrobial Activity of Selenium Nanoparticles With Different Surface Chemistry and Structure - Filipović, Nenad; Ušjak, Dušan; Milenković, Marina T.; Zheng, Kai; Liverani, Liliana; Boccaccini, Aldo R.; Stevanović, Magdalena M. (Frontiers in Bioengineering and Biotechnology, 2021)
Although selenium nanoparticles (SeNPs) have gained attention in the scientific community mostly through investigation of their anticancer activity, a great potential of this nanomaterial was recognized recently regarding its antimicrobial activity. The particle form, size, and surface chemistry have been recognized as crucial parameters determining the interaction of nanomaterials with biological entities. Furthermore, considering a narrow boundary between beneficial and toxic effects for selenium per se, it is clear that investigations of biomedical applications of SeNPs are very demanding and must be done with great precautions. The goal of this work is to evaluate the effects of SeNPs surface chemistry and structure on antimicrobial activity against several common bacterial strains, including Staphylococcus aureus (ATCC 6538), Enterococcus faecalis (ATCC 29212), Bacillus subtilis (ATCC 6633), and Kocuria rhizophila (ATCC 9341), as well as Escherichia coli (ATCC 8739), Salmonella Abony (NCTC 6017), Klebsiella pneumoniae (NCIMB 9111) and Pseudomonas aeruginosa (ATCC 9027), and the standard yeast strain Candida albicans (ATCC 10231). Three types of SeNPs were synthesized by chemical reduction approach using different stabilizers and reducing agents: (i) bovine serum albumin (BSA) + ascorbic acid, (ii) chitosan + ascorbic acid, and (iii) with glucose. A thorough physicochemical characterization of the obtained SeNPs was performed to determine the effects of varying synthesis parameters on their morphology, size, structure, and surface chemistry. All SeNPs were amorphous, with spherical morphology and size in the range 70–300 nm. However, the SeNPs obtained under different synthesis conditions, i.e. by using different stabilizers as well as reducing agents, exhibited different antimicrobial activity as well as cytotoxicity which are crucial for their applications. In this paper, the antimicrobial screening of the selected systems is presented, which was determined by the broth microdilution method, and inhibitory influence on the production of monomicrobial and dual-species biofilm was evaluated. The potential mechanism of action of different systems is proposed. Additionally, the cytotoxicity of SeNPs was examined on the MRC-5 cell line, in the same concentration interval as for antimicrobial testing. It was shown that formulation SeNPs-BSA expressed a significantly lower cytotoxic effect than the other two formulations.
CRIS-Team Scopus Importer:2021-02-26
Keywords: antimicrobial activity; dual-species biofilm; inhibition of biofilms; nanocomposites; selenium nanoparticles (SeNPs)

Comparison between the Astaxanthin Release Profile of Mesoporous Bioactive Glass Nanoparticles (MBGNs) and Poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV)/MBGN Composite Microspheres - Aguilar Rabiela, Arturo Elias; Homaeigohar, Shahin; González-Castillo, Eduin I.; Sanchez, Mirna; Boccaccini, Aldo R. (Polymers, 2023)
In recent years, composite biomaterials have attracted attention for drug delivery applications due to the possibility of combining desired properties of their components. However, some functional characteristics, such as their drug release efficiency and likely side effects, are still unexplored. In this regard, controlled tuning of the drug release kinetic via the precise design of a composite particle system is still of high importance for many biomedical applications. This objective can be properly fulfilled through the combination of different biomaterials with unequal release rates, such as mesoporous bioactive glass nanoparticles (MBGN) and poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) microspheres. In this work, MBGNs and PHBV-MBGN microspheres, both loaded with Astaxanthin (ASX), were synthesised and compared in terms of ASX release kinetic, ASX entrapment efficiency, and cell viability. Moreover, the correlation of the release kinetic to phytotherapeutic efficiency and side effects was established. Interestingly, there were significant differences between the ASX release kinetic of the developed systems, and cell viability differed accordingly after 72 h. Both particle carriers effectively delivered ASX, though the composite microspheres exhibited a more prolonged release profile with sustained cytocompatibility. The release behaviour could be fine-tuned by adjusting the MBGN content in the composite particles. Comparatively, the composite particles induced a different release effect, implying their potential for sustained drug delivery applications.
CRIS-Team Scopus Importer:2023-06-23
Keywords: Astaxanthin; composite microspheres; controlled release; sustained release

Comparison of hydrogels for the development of well-defined 3d cancer models of breast cancer and melanoma - Schmid, Rafael; Schmidt, Sonja; Hazur, Jonas; Detsch, Rainer; Maurer, Evelyn; Boccaccini, Aldo R.; Hauptstein, Julia; Teßmar, Jörg; Blunk, Torsten; Schrüfer, Stefan; Schubert, Dirk W.; Horch, Raymund E.; et al. (Cancers, 2020)
Bioprinting offers the opportunity to fabricate precise 3D tumor models to study tumor pathophysiology and progression. However, the choice of the bioink used is important. In this study, cell behavior was studied in three mechanically and biologically different hydrogels (alginate, alginate dialdehyde crosslinked with gelatin (ADA–GEL), and thiol-modified hyaluronan (HA-SH crosslinked with PEGDA)) with cells from breast cancer (MDA-MB-231 and MCF-7) and melanoma (Mel Im and MV3), by analyzing survival, growth, and the amount of metabolically active, living cells via WST-8 labeling. Material characteristics were analyzed by dynamic mechanical analysis. Cell lines revealed significantly increased cell numbers in low-percentage alginate and HA-SH from day 1 to 14, while only Mel Im also revealed an increase in ADA–GEL. MCF-7 showed a preference for 1% alginate. Melanoma cells tended to proliferate better in ADA– GEL and HA-SH than mammary carcinoma cells. In 1% alginate, breast cancer cells showed equally good proliferation compared to melanoma cell lines. A smaller area was colonized in high-percentage alginate-based hydrogels. Moreover, 3% alginate was the stiffest material, and 2.5% ADA–GEL was the softest material. The other hydrogels were in the same range in between. Therefore, cellular responses were not only stiffness-dependent. With 1% alginate and HA-SH, we identified matrices that enable proliferation of all tested tumor cell lines while maintaining expected tumor heterogeneity. By adapting hydrogels, differences could be accentuated. This opens up the possibility of understanding and analyzing tumor heterogeneity by biofabrication.
CRIS-Team Scopus Importer:2020-08-28
Keywords: Biofabrication; Breast cancer; Hydrogel; Melanoma; Tumor heterogeneity

Comparison of microstructure, sintering behavior, and biological response of sol-gel and melt-derived 13–93 bioactive glass scaffolds - Nawaz, Qaisar; de Pablos-Martín, A.; Contreras Jaimes, A. T.; Scheffler, F.; Wagner, T.; Brauer, D. S.; Boccaccini, Aldo R. (Open Ceramics, 2023)
In this study, 13–93 bioactive glass (BG) powders were obtained through the traditional melt-quenching and sol-gel approaches and were used to fabricate scaffolds using the well-known foam replica technique. A comparative analysis of scaffolds prepared using sol-gel and melt-derived powders was carried out. The microstructure of scaffolds was examined by scanning electron microscopy (SEM) and X-ray computed tomography. The shrinkage behavior of the scaffold structure during sintering was investigated using heating microscopy (HM). The bioactivity results indicated the formation of a hydroxyapatite layer on the surface of both scaffolds after immersion in simulated body fluid (SBF) for 7 days. In vitro cell viability results revealed that both scaffolds are cytocompatible with MG-63 cells (osteoblast-like cell line). The findings indicate that sol-gel glass-derived 13–93 scaffolds exhibited similar characteristics to the well-known melt-derived 13–93 scaffolds. Moreover, the low-temperature processing and high purity associated with the sol-gel approach suggest that sol-gel derived 13–93 BG powder is attractive for fabricating high-quality scaffolds.
CRIS-Team Scopus Importer:2023-08-04
Keywords: 13-93 bioactive glass; Bioactivity; Heating microscopy; Micro-CT; Sol-gel glass-based scaffolds

Comparison of nanoscale and microscale bioactive glass on the properties of P(3HB)/Bioglass (R) composites - Misra, Superb K.; Mohn, Dirk; Brunner, Tobias J.; Stark, Wendelin J.; Philip, Sheryl E.; Roy, Ipsita; Salih, Vehid; Knowles, Jonathan C.; Boccaccini, Aldo R. (Biomaterials, 2008)
This study compares the effects of introducing micro (m-BG) and nanoscale (n-BG) bioactive glass particles on the various properties (thermal, mechanical and microstructural) of poly(3hydroxybutyrate) (P(3HB))/bioactive glass composite systems. P(3HB)/bioactive glass composite films with three different concentrations of m-BG and n-BG (10, 20 and 30 wt%, respectively) were prepared by a solvent casting technique. The addition of n-BG particles had a significant stiffening effect on the composites, modulus when compared with m-BG. However, there were no significant differences in the thermal properties of the composites due to the addition of n-BG and m-BG particles. The systematic addition of n-BG particles induced a nanostructured topography on the surface of the composites, which was not visible by SEM in m-BG composites. This surface effect induced by n-BG particles considerably improved the total protein adsorption on the n-BG composites compared to the unfilled polymer and the m-BG composites. A short term in vitro degradation (30 days) study in simulated body fluid (SBF) showed a high level of bioactivity as well as higher water absorption for the P(3HB)/n-BG composites. Furthermore, a cell proliferation study using MG-63 cells demonstrated the good biocompatibility of both types of P(3HB)/bioactive glass composite systems. The results of this investigation confirm that the addition of nanosized bioactive glass particles had a more significant effect on the mechanical and structural properties of a composite system in comparison with microparticles, as well as enhancing protein adsorption, two desirable effects for the application of the composites in tissue engineering. © 2008 Elsevier Ltd. All rights reserved.
UnivIS-Import:2015-03-09:Pub.2008.tech.IW.LM.compar
Keywords: Bioactive composites; Bioactive glass; MG-63 osteoblasts; Nanoparticles; Osteoblast; Poly(3hydroxybutyrate)

Comparison of rapid and slow sintered pulverised fuel ash - Adell, V.; Cheeseman, C. R.; Doel, A.; Beattie, A.; Boccaccini, Aldo R. (Fuel, 2008)
This study has investigated the properties of sintered PFA using conventional (20 °C/min) and rapid heating rates. Rapid heating was achieved by directly placing pressed PFA samples into a furnace preset at the sintering temperature. Slow sintered PFA samples show an increase in shrinkage and fired density and a reduction in water absorption as the sintering temperature increases, with maximum density obtained at around 1250 °C. At higher temperatures samples show a bloating effect associated with the enlargement of closed porosity. This peak in density is not observed in rapidly sintered PFA. Rapid sintering at temperatures between 1150 °C and 1300 °C resulted in constant values of shrinkage (6.5%), fired density (1.4 g/cm3) and water absorption (15%). During rapid sintering the residual carbon in the PFA is present in the sample at the sintering temperature whereas conventional sintering removes the carbon at lower temperatures before sintering occurs. Rapid sintering also retains significant carbon in the core of the sintered sample. This carbon is believed to act as rigid inclusions that inhibit PFA sintering, limiting shrinkage and densification. Rapid sintering is associated with black coring which is also characteristic in lightweight aggregate manufactured from PFA sintered on a sinter strand. The rapid heating rate experienced by PFA pellets on a sinter strand and the associated inhibition of sintering by carbon is essential for producing sintered PFA products with properties appropriate for use as lightweight aggregate. © 2007 Elsevier Ltd. All rights reserved.
UnivIS-Import:2015-03-09:Pub.2008.tech.IW.LM.compar_0
Keywords: Ceramics; Lightweight aggregate; Pulverised fuel ash; Sinter strand; Unburned carbon

Comparison of the Behavior of 3D-Printed Endothelial Cells in Different Bioinks - Schulik, Jana; Salehi, Sahar; Boccaccini, Aldo R.; Schrüfer, Stefan; Schubert, Dirk W.; Arkudas, Andreas; Kengelbach-Weigand, Annika; Horch, Raymund E.; Schmid, Rafael (Bioengineering, 2023)
Biomaterials with characteristics similar to extracellular matrix and with suitable bioprinting properties are essential for vascular tissue engineering. In search for suitable biomaterials, this study investigated the three hydrogels alginate/hyaluronic acid/gelatin (Alg/HA/Gel), pre-crosslinked alginate di-aldehyde with gelatin (ADA-GEL), and gelatin methacryloyl (GelMA) with respect to their mechanical properties and to the survival, migration, and proliferation of human umbilical vein endothelial cells (HUVECs). In addition, the behavior of HUVECs was compared with their behavior in Matrigel. For this purpose, HUVECs were mixed with the inks both as single cells and as cell spheroids and printed using extrusion-based bioprinting. Good printability with shape fidelity was determined for all inks. The rheological measurements demonstrated the gelling consistency of the inks and shear-thinning behavior. Different Young’s moduli of the hydrogels were determined. However, all measured values where within the range defined in the literature, leading to migration and sprouting, as well as reconciling migration with adhesion. Cell survival and proliferation in ADA-GEL and GelMA hydrogels were demonstrated for 14 days. In the Alg/HA/Gel bioink, cell death occurred within 7 days for single cells. Sprouting and migration of the HUVEC spheroids were observed in ADA-GEL and GelMA. Similar behavior of the spheroids was seen in Matrigel. In contrast, the spheroids in the Alg/HA/Gel ink died over the time studied. It has been shown that Alg/HA/Gel does not provide a good environment for long-term survival of HUVECs. In conclusion, ADA-GEL and GelMA are promising inks for vascular tissue engineering.
CRIS-Team Scopus Importer:2023-08-11
Keywords: biofabrication; bioprinting; endothelial cells; hydrogels; tissue engineering; vascularization

Comparison of the effects of 45S5 and 1393 bioactive glass microparticles on hMSC behavior - Qazi, Taimoor H.; Hafeez, Shahzad; Schmidt, Jochen; Duda, Georg N.; Boccaccini, Aldo R.; Lippens, Evi (Journal of Biomedical Materials Research Part A, 2017)
Keywords: bioactive glass; cell function; hMSCs; ion release; microparticles

Comparison of the influence of 45s5 and Cu-containing 45s5 bioactive glass (BG) on the biological properties of novel Polyhydroxyalkanoate (PHA)/BG composites - Schuhladen, Katharina; Lukasiewicz, Barbara; Basnett, Pooja; Roy, Ipsita; Boccaccini, Aldo R. (Materials, 2020)
Polyhydroxyalkanoates (PHAs), due to their biodegradable and biocompatible nature and their ability to be formed in complex structures, are excellent candidates for fabricating scaffolds used in tissue engineering. By introducing inorganic compounds, such as bioactive glasses (BGs), the bioactive properties of PHAs can be further improved. In addition to their outstanding bioactivity, BGs can be additionally doped with biological ions, which in turn extend the functionality of the BG-PHA composite. Here, different PHAs were combined with 45S5 BG, which was additionally doped with copper in order to introduce antibacterial and angiogenic properties. The resulting composite was used to produce scaffolds by the salt leaching technique. By performing indirect cell biology tests using stromal cells, a dose-depending effect of the dissolution products released from the BG-PHA scaffolds could be found. In low concentrations, no toxic effect was found. Moreover, in higher concentrations, a minor reduction of cell viability combined with a major increase in VEGF release was measured. This result indicates that the fabricated composite scaffolds are suitable candidates for applications in soft and hard tissue engineering. However, more in-depth studies are necessary to fully understand the release kinetics and the resulting long-term effects of the BG-PHA composites.
CRIS-Team Scopus Importer:2020-07-03
Keywords: Bioactive glass; Copper; Polyhydroxyalkanoates; Scaffolds; Tissue engineering

Complex mechanical behavior of human articular cartilage and hydrogels for cartilage repair - Weizel, A.; Distler, Thomas; Schneidereit, Dominik; Friedrich, Oliver; Bräuer, Lars; Paulsen, Friedrich; Detsch, Rainer; Boccaccini, Aldo R.; Budday, Silvia; Seitz, H. (Acta Biomaterialia, 2020)
The mechanical behavior of cartilage tissue plays a crucial role in physiological mechanotransduction processes of chondrocytes and pathological changes like osteoarthritis. Therefore, intensive research activities focus on the identification of implant substitute materials that mechanically mimic the cartilage extracellular matrix. This, however, requires a thorough understanding of the complex mechanical behavior of both native cartilage and potential substitute materials to treat cartilage lesions. Here, we perform complex multi-modal mechanical analyses of human articular cartilage and two surrogate materials, commercially available ChondroFillerliquid, and oxidized alginate-gelatin (ADA-GEL) hydrogels. We show that all materials exhibit nonlinearity and compression-tension asymmetry. However, while hyaline cartilage yields higher stresses in tension than in compression, ChondroFillerliquid and ADA-GEL exhibit the opposite trend. These characteristics can be attributed to the materials’ underlying microstructure: Both cartilage and ChondroFillerliquid contain fibrillar components, but the latter constitutes a bi-phasic structure, where the 60% nonfibrillar hydrogel proportion dominates the mechanical response. Of all materials, ChondroFillerliquid shows the most pronounced viscous effects. The present study provides important insights into the microstructure-property relationship of cartilage substitute materials, with vital implications for mechanically-driven material design in cartilage engineering. In addition, we provide a data set to create mechanical simulation models in the future.
CRIS-Team Scopus Importer:2020-11-06
Keywords: Human articular cartilage; Hydrogels; Mechanical testing; Microstructure; Tissue engineering

Composite Alginate Dialdehyde-Gelatin (ADA-GEL) Hydrogel Containing Short Ribbon-Shaped Fillers for Skeletal Muscle Tissue Biofabrication - Sprenger, Lys; Lu, Hsuan-Heng; Trippmacher, Steffen; Mansfeld, Ulrich; Milkin, Pavel; Ionov, Leonid; Papastavrou, Georg; Boccaccini, Aldo R.; Salehi, Sahar (ACS Applied Materials and Interfaces, 2024)
Skeletal muscle tissue can be severely damaged by disease or trauma beyond its ability to self-repair, necessitating the further development of biofabrication and tissue-engineering tools for reconstructive processes. Hence, in this study, a composite bioink of oxidized alginate (ADA) and gelatin (GEL) including cell-laden ribbon-shaped fillers is used for enhancing cell alignment and the formation of an anisotropic structure. Different plasma treatments combined with protein coatings were evaluated for the improvement of cell adhesion to poly(lactic-co-glycolic acid) (PLGA) ribbon surfaces. Oxygen plasma activation of 30 W for 5 min showed high immobilization of fibronectin as a protein coating on the PLGA ribbon surface, which resulted in enhanced cell adhesion and differentiation of muscle cells. Furthermore, the effect of various concentrations of CaCl2 solution, used for ionic cross-linking of ADA, on ADA-GEL physical and mechanical properties as well as encapsulated C2C12 cell viability and proliferation behavior was investigated. The pore area was measured via two approaches, cryofixation and lyophilization, which, in accordance with degradation tests and mechanical analysis, showed that 60 mM CaCl2 concentration is the optimum range for cross-linking of the formulation of ADA 2.5%w/v-GEL 3.75%w/v. These cross-linked hydrogels showed a compression modulus of 11.5 kPa (similar to the native skeletal muscle tissue), a high viability of C2C12 muscle cells (>80%), and a high proliferation rate during 7 days of culture. Rheological characterization of the ADA-GEL composite hydrogel containing short fillers (100 μm long) showed its suitability as a bioink with shear-thinning and flow behavior compared to ADA-GEL.
CRIS-Team Scopus Importer:2024-09-13
Keywords: ADA-GEL; cell carriers; composite; plasma treatment; tissue engineering

Composite Colloidal Gels Made of Bisphosphonate-Functionalized Gelatin and Bioactive Glass Particles for Regeneration of Osteoporotic Bone Defects - Diba, Mani; Camargo, Winston A.; Brindisi, Mariateresa; Farbod, Kambiz; Klymov, Alexey; Schmidt, Stephan; Harrington, Matthew J.; Draghi, Lorenza; Boccaccini, Aldo R.; Jansen, John A.; van den Beucken, Jeroen J.J.P.; Leeuwenburgh, Sander C.G. (Advanced Functional Materials, 2017)
Keywords: biomedical applications; colloids; composite materials; hydrogels; self-healing

Composite materials of amorphous calcium phosphate and bioactive glass nanoparticles for preventive dentistry - Degli Esposti, Lorenzo; Zheng, Kai; Piancastelli, Andreana; Ionescu, Andrei C.; Adamiano, Alessio; Boccaccini, Aldo R.; Iafisco, Michele (Ceramics International, 2023)
Amorphous calcium phosphates and bioactive glasses are two of the most used materials in dentistry thanks to their ability to release remineralizing ions and reduce dentinal hypersensitivity by occluding exposed dentinal tubules. Here, we have synthesized composites of fluoride-doped amorphous calcium phosphate (FACP) and mesoporous bioactive glass nanoparticles (MBGNs) to obtain functional materials that possess both the capability to release dental remineralizing ions of FACP and both the excellent desensitizing activity of MBGNs. The procedure described in this work allows us to obtain FACP/MBGN composites with different compositions (i.e., FACP:MBGN weight ratio) in which the components have formed a deeply intertwined nanostructure. Composites’ ion release (i.e. Ca, P, F, and Si) in acidic artificial saliva is different from that of the single components or their physical mixture, corroborating the formation of composite materials. Moreover, thanks to the presence of FACP, the composites have superior bioactivity than the MBGNs alone. Dental enamel remineralization and efficacy of dentinal tubules occlusion by the investigated composites were preliminarily tested in vitro on human dental hard tissues using scanning electron microscopy. Data revealed that the composites induced a satisfactory remineralization of enamel and dentin thanks to the FACP component, and a positive tubule occlusion thanks to the MBGNs component. Finally, our results demonstrate that FACP/MBGN composites are highly promising materials for preventive dentistry.
CRIS-Team Scopus Importer:2023-10-27
Keywords: Apatite; Biomedical application; Glass ceramics; Nanocomposites

Composite polymer-bioceramic scaffolds with drug delivery capability for bone tissue engineering - Mourino, Viviana; Cattalini, Juan P.; Roether, Judith; Dubey, Prachi; Roy, Ipsita; Boccaccini, Aldo R. (Expert Opinion on Drug Delivery, 2013)
Introduction: Next-generation scaffolds for bone tissue engineering (BTE) should exhibit the appropriate combination of mechanical support and morphological guidance for cell proliferation and attachment while at the same time serving as matrices for sustained delivery of therapeutic drugs and/or biomolecular signals, such as growth factors. Drug delivery from BTE scaffolds to induce the formation of functional tissues, which may need to vary temporally and spatially, represents a versatile approach to manipulating the local environment for directing cell function and/or to treat common bone diseases or local infection. In addition, drug delivery from BTE is proposed to either increase the expression of tissue inductive factors or to block the expression of others factors that could inhibit bone tissue formation. Composite scaffolds which combine biopolymers and bioactive ceramics in mechanically competent 3D structures, including also organic-inorganic hybrids, are being widely developed for BTE, where the affinity and interaction between biomaterials and therapeutic drugs or biomolecular signals play a decisive role in controlling the release rate. Areas covered: This review covers current developments and applications of 3D composite scaffolds for BTE which exhibit the added capability of controlled delivery of therapeutic drugs or growth factors. A summary of drugs and biomolecules incorporated in composite scaffolds and approaches developed to combine biopolymers and bioceramics in composites for drug delivery systems for BTE is presented. Special attention is given to identify the main challenges and unmet needs of current designs and technologies for developing such multifunctional 3D composite scaffolds for BTE. Expert opinion: One of the major challenges for developing composite scaffolds for BTE is the incorporation of a drug delivery function of sufficient complexity to be able to induce the release patterns that may be necessary for effective osseointegration, vascularization and bone regeneration. Loading 3D scaffolds with different biomolecular agents should produce a codelivery system with different, predetermined release profiles. It is also envisaged that the number of relevant bioactive agents that can be loaded onto scaffolds will be increased, whilst the composite scaffold design should exploit synergistically the different degradation profiles of the organic and inorganic components. © 2013 Informa UK, Ltd.
UnivIS-Import:2015-03-09:Pub.2013.tech.IW.LM.compos
Keywords: Bone tissue engineering; Composite scaffolds; Drug delivery

Composites Containing Bioactive Glass - Boccaccini, Aldo R.; et al. (John Wiley and Sons, 2012)
Keywords: Bioactive glass in scaffolds for bone regeneration; Bioactive-glass-containing scaffolds; for bone defects; Biodegradable polymers; Composites; biodegradable polymers and bioactive glass; Composites; containing bioactive glasses; PDLLA-Bioglass composite system; Polyester matrix composites and bioactive glass by TIPS; Porous bioactive composite; processing technologies; Synthetic bone grafts; and requirements; Synthetic bone substitutes replacing transplanted bone

Controlled Delivery of Gentamicin Using Poly(3-hydroxybutyrate) Microspheres - Francis, Lydia; Meng, Decheng; Knowles, Jonathan; Keshavarz, Tajalli; Boccaccini, Aldo R.; Roy, Ipsita (International Journal of Molecular Sciences, 2011)
Poly(3-hydroxybutyrate), P(3HB), produced from Bacillus cereus SPV using a simple glucose feeding strategy was used to fabricate P(3HB) microspheres using a solid-in-oil-water (s/o/w) technique. For this study, several parameters such as polymer concentration, surfactant and stirring rates were varied in order to determine their effect on microsphere characteristics. The average size of the microspheres was in the range of 2 μm to 1.54 μm with specific surface areas varying between 9.60 m 2/g and 6.05 m 2/g. Low stirring speed of 300 rpm produced slightly larger microspheres when compared to the smaller microspheres produced when the stirring velocity was increased to 800 rpm. The surface morphology of the microspheres after solvent evaporation appeared smooth when observed under SEM. Gentamicin was encapsulated within these P(3HB) microspheres and the release kinetics from the microspheres exhibiting the highest encapsulation efficiency, which was 48%, was investigated. The in vitro release of gentamicin was bimodal, an initial burst release was observed followed by a diffusion mediated sustained release. Biodegradable P(3HB) microspheres developed in this research has shown high potential to be used in various biomedical applications. © 2011 by the authors.
UnivIS-Import:2015-03-09:Pub.2011.tech.IW.LM.contro
Keywords: Controlled drug delivery; Gentamicin; Microspheres; Poly(3-hydroxybutyrate)

Copper-doped cotton-like malleable electrospun bioactive glass fibers for wound healing applications - Liverani, Liliana; Reiter, Theresa; Zheng, Kai; Neščáková, Zuzana; Boccaccini, Aldo R. (Materials Letters: X, 2022)
The combination of electrospinning and sol-gel methods is attracting the interest of the scientific community for developing three-dimensional bioactive glass (BG)-based fibers. This paper reports the fabrication of cotton-like copper-doped BG fibers by combining electrospinning and sol-gel techniques. Acellular bioactivity in simulated body fluid, ion release, cell viability and scratch cell tests were performed. Results showed that copper was successfully incorporated in the fibers and Cu ions were released in limited concentration over seven days. The presence of copper delayed the mineralization of the fibers upon immersion in simulated body fluid (SBF), but it did not affect keratinocyte viability and migration. Wound closure in the scratch cell test was achieved in 48 h for all the investigated samples.
CRIS-Team Scopus Importer:2022-03-18
Keywords: Bioactive glass; Copper; Electrospinning; Sol-gel; Wound healing

Copper releasing boron containing bioactive glass-based scaffolds coated with alginate for bone tissue engineering - Erol, M. M.; Mournio, V.; Newby, P.; Chatzistavrou, Xanthippi; Roether, Judith; Hupa, L.; Boccaccini, Aldo R. (Acta Biomaterialia, 2012)
The aim of this study was to synthesize and characterize new boron-containing bioactive glass-based scaffolds coated with alginate cross-linked with copper ions. A recently developed bioactive glass powder with nominal composition (wt.%) 65 SiO 2, 15 CaO, 18.4 Na 2O, 0.1 MgO and 1.5 B 2O 3 was fabricated as porous scaffolds by the foam replica method. Scaffolds were alginate coated by dipping them in alginate solution. Scanning electron microscopy investigations indicated that the alginate effectively attached on the surface of the three-dimensional scaffolds leading to a homogeneous coating. It was confirmed that the scaffold structure remained amorphous after the sintering process and that the alginate coating improved the scaffold bioactivity and mechanical properties. Copper release studies showed that the alginate-coated scaffolds allowed controlled release of copper ions. The novel copper-releasing composite scaffolds represent promising candidates for bone regeneration. © 2011 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
UnivIS-Import:2015-03-09:Pub.2012.tech.IW.LM.copper
Keywords: Alginate; Antibacterial; Bioactive glass; Cu ion release; Scaffolds

Correction: Ga and Ce ion-doped phosphate glass fibres with antibacterial properties and their composite for wound healing applications (Journal of Materials Chemistry B (2019) DOI: 10.1039/c9tb00820a) - Lapa, Agata; Cresswell, Mark; Campbell, Ian; Jackson, Phil; Goldmann, Wolfgang; Detsch, Rainer; Parsons, Andrew; Ahmed, Ifty; Boccaccini, Aldo R. (Journal of Materials Chemistry B, 2019)
The authors regret that in the original article the affiliation list is presented incorrectly. The corrected list is shown above. This change does not affect the affiliation tags used in the author list, which therefore remain the same. The Royal Society of Chemistry apologises for these errors and any consequent inconvenience to authors and readers.
CRIS-Team Scopus Importer:2019-12-03

Corrigendum to “Preparation and characterization of novel poly (lactic acid)/calcium oxide nanocomposites by electrospinning as a potential scaffold for bone tissue engineering” [Biomater. Adv. (2023) 153, 213578] (Biomaterials Advances (2023) 153, (S2772950823003011), (10.1016/j.bioadv.2023.213578)) - Canales, Daniel; Moyano, Dominique; Alvarez, Fabian; Grande-Tovar, Carlos David; Valencia-Llano, Carlos H.; Peponi, Laura; Boccaccini, Aldo R.; Zapata, Paula A. (Biomaterials Advances, 2023)
The authors regret <insert corrigendum text>. In the article, is necessary to add a new affiliation, specifically for the co-author Carlos H. Valencia-Llano. The new affiliation is: Grupo Biomateriales Dentales, Escuela de Odontología, Universidad del Valle, Calle 4B # 36-00, Cali 76001, Colombia Considering this modification, the new section of authors and affiliation would be: Daniel Canales1,2⁎, Dominique Moyano1, Fabian Alvarez2, Carlos David Grande-Tovar3, Carlos H. Valencia-Llano4, Laura Peponi5, Aldo R. Boccaccini6,7, Paula A. Zapata 1* 1Grupo Polímeros, Departamento de Ciencias del Ambiente, Facultad de Química y Biología, Universidad de Santiago de Chile, USACH, Casilla 40, Correo 33, Santiago, Chile. (daniel.canales@usach.cl)(paula.zapata@usach.cl) 2Laboratorio de biomecánica y biomateriales, Departamento de ingeniería mecánica, Facultad de ingeniería, Universidad de Santiago de Chile, USACH, Santiago, Chile 3Research Group of Fotoquímica y Fotobiología, Universidad del Atlántico, Carrera 30 Número 8-49, Puerto Colombia 081008, Colombia 4Grupo Biomateriales Dentales, Escuela de Odontología, Universidad del Valle, Calle 4B # 36-00, Cali 76001, Colombia 5Instituto de Ciencia y Tecnología de Polímeros (ICTP-CSIC), Madrid, España 6Department of Materials Science and Engineering, Institute of Biomaterials, Friedrich- Alexander-University Erlangen-Nuremberg, Erlangen, Germany 7Bavarian Polymer Institute, 91058Erlangen, Germany The authors would like to apologise for any inconvenience caused.
CRIS-Team Scopus Importer:2023-09-22

Corrosion behavior of biodegradable metals in two different simulated physiological solutions: Comparison of Mg, Zn and Fe - Dong, Hongzhou; Lin, Fei; Boccaccini, Aldo R.; Virtanen, Sannakaisa (Corrosion Science, 2021)
Bio-absorbable metals have been proposed to overcome the limitations of permanent implant materials, particularly the risk of chronic inflammation and secondary surgery for removal after healing. The most researched bio-absorbable metal is magnesium, followed by iron and zinc, but there is little work comparing the different metals under the same experimental conditions. Herein, degradation performance of Mg/Zn/Fe was investigated via immersion test (28 days) and electrochemical tests under two buffer systems, simulated body fluid solution (SBF) and Dulbecco's Modified Eagle's cell culture medium (DMEM). Corrosion rate was initially slower in DMEM for all metals, Mg showed the fastest corrosion rate in both SBF and DMEM. The influence of the electrolyte on the corrosion behaviour was strongest for Mg. Importantly, the ranking of the corrosion rate of the three metals changes with immersion time. Noteworthy is a strong increase of corrosion resistance of Mg with time during the first 24 h of immersion. Corrosion morphology and corrosion products were characterized with SEM, EDS, FTIR, XPS and XRD. In general, the corrosion product layers are much more uniform in DMEM, besides, the insoluble corrosion product/precipitation consisted of metallic oxides/hydroxides, phosphates and carbonates. Slower corrosion rate in DMEM solution can therefore be due to formation of a more protective precipitate layer, adsorbed amino acids, and absence of Tris-HCl that accelerates corrosion in SBF.
CRIS-Team Scopus Importer:2021-02-05
Keywords: Bioactivity; Biodegradable metals; Corrosion; Iron; Magnesium; Zinc

Corrosion behaviour, metal release and biocompatibility of implant materials coated by TiO2-sol gel chemistry - Detsch, Rainer; et al. (Biomedizinische Technik, 2005)
Alloys based on titanium or cobalt have been used as implant materials for decades with good success. Because of their natural oxide layer these alloys reveal good corrosion behaviour. In contact with physiological solution metal release takes place, which can cause inflammation. Coatings can improve the corrosion behaviour. In this study Ti6Al4V and Co28Cr6Mo alloys, which are frequently used as implant materials, were tested. Polished discs of these alloys and polished discs, which were coated with TiO-layers by sol-gel chemistry, were compared regarding their corrosion behaviour and metal ion releasing. The releasing of Al, V, Ti, Co, Cr and Mo was quantified by ICP-MS analysis. The TiO-coating reduced the release of all ions except of the Al-ion. Both alloys showed a deviating kinetic of ion releasing. In addition, cell response (cell vitality, cell proliferation, endothelial marker CD31 and actin allocation) of osteoblasts and endothelial cells were investigated.
Keywords: In vitro cell test; Ion release; Ti6Al4V- and Co28Cr6Mo-alloys; TiO2-coating

Corrosion of Mg alloy AZ91D in the presence of living cells - Virtanen, Sannakaisa; Seuß, Sigrid; Fabry, Ben; Turhan, Can Metehan; Seuß, Florian (Journal of Biomedical Materials Research Part B: Applied Biomaterials, 2011)

Corrosion Resistance Study of Electrophoretic Deposited Hydroxyapatite on Stainless Steel for Implant Applications - Chew, Kean-Khoon; Zein, Sharif Hussein Sharif; Ahmad, Abdul Latif; McPhail, David S.; Boccaccini, Aldo R. (Key Engineering Materials, 2012)
Stainless steel (SS) is often used for orthopaedic and dental implants because of its excellent mechanical characteristics. However, from an electrochemical perspective, SS can be susceptible to corrosion-related problems. Inorganic bioactive coatings on SS surfaces are reported to impart corrosion resistance and enhance biocompatibility. In this paper, hydroxyapatite (HA) coatings were developed on SS 316L by an electrophoretic deposition (EPD) technique at applied deposition voltages from 10 to 60 V in an acidic aqueous solution. The present study was performed to optimise the applied voltage required to produce stable HA coatings on SS 316L. Their corrosion resistance in simulated body conditions were investigated using the potentiodynamic polarization curves. The results of the electrochemical studies revealed that the optimal applied voltage for EPD of HA on SS 316L was 40 V. The polarisation parameters, such as the corrosion potential, breakdown potential and repassivation potential of HA coated materials demonstrated nobler behaviours than the uncoated SS 316L. These results validated the successful formation of stable and protective HA coatings on SS 316L. © (2012) Trans Tech Publications, Switzerland.
UnivIS-Import:2015-03-09:Pub.2012.tech.IW.LM.corros
Keywords: Corrosion resistance; Electrochemical study; Electrophoretic deposition; Hydroxyapatite; Stainless steel

Cotton-wool-like borosilicate glass fibers for tissue regeneration: Preparation, characterization and in vitro bioactivity - Sengupta, Susanta; Liverani, Liliana; Galusek, Dušan; Boccaccini, Aldo R. (Open Ceramics, 2023)
Borosilicate (60SiO2-20CaO-16B2O3-4P2O5) glass fibers (BSGF) were fabricated by electrospinning in combination with sol-gel processing. BSGF were calcined at 600, 700 and 800 °C to remove the polymeric binder and optimize the formation of the inorganic phase. HCA (hydroxycarbonate apatite) was formed on BSGF within 24h of immersion in simulated body fluid (SBF), which was confirmed by XRD and FTIR analyses. In vitro cytotoxicity was measured with mouse osteoblast and fibroblast cell lines. WST-8 assay and fluorescence images confirmed the non-cytotoxic nature of the BSGF which did not induce any adverse effect on the cell activity.
CRIS-Team Scopus Importer:2023-11-03
Keywords: Bioactive glass; Electrospinning; Sol-gel

Cotton wool-like ion-doped bioactive glass nanofibers: investigation of Zn and Cu combined effect - Ünalan, Irem; Rimoli, Ian Heit; Mutlu, Nurshen; Michálek, Martin; Abraham, Gustavo A.; Liverani, Liliana; Boccaccini, Aldo R. (Biomedical Materials (Bristol), 2024)
Electrospinning is a versatile and straightforward technique to produce nanofibrous mats with different morphologies. In addition, by optimizing the solution, processing, and environmental parameters, three-dimensional (3D) nanofibrous scaffolds can also be created using this method. In this work, the preparation and characterization of bioactive glass (BG) scaffolds based on the SiO2-CaO sol-gel system, a biomaterial with a highly reactive surface, is reported. The electrospinning technique was combined with sol-gel methods to obtain nanofibrous 3D cotton wool-like scaffolds. The addition of zinc and copper ions to the silica-calcia system was examined, and the influence of these ions on the material properties and characteristics was investigated by various characterization techniques, from morphological and chemical properties to antibacterial and wound closure capability, cell viability and ion release. Our findings show that the cotton wool-like ion-doped nanofibers are promising for wound healing applications.
CRIS-Team Scopus Importer:2024-09-13
Keywords: copper; cotton wool-like electrospun nanofibers; sol-gel synthesis; wound healing; zinc

Crack growth in glass matrix composite reinforced by long SiC fibres - Kotoul, Michal; Vyslouzil, Tomas; Boccaccini, Aldo R.; Dlouhy, Ivo (Theoretical and Applied Fracture Mechanics, 2008)
Theoretical and experimental work are made for bridged cracks in chevron-notched three point bend specimens made of glass matrix composite reinforced by long SiC fibres. The fracture toughness (KIC) values are determined using the chevron-notch technique and compared with the theoretical predictions based on micromechanical analysis exploiting weight functions. The weight functions for orthotropic material are obtained numerically by means of detailed FEM analysis using the ANSYS package and they are further used together with appropriate bridging models for the theoretical prediction of the R-curve behaviours typical of the investigated composites. © 2007 Elsevier Ltd. All rights reserved.
UnivIS-Import:2015-03-09:Pub.2008.tech.IW.LM.crackg
Keywords: Brittle matrix composites; Chevron-notch specimen; Crack bridging; R-curve modelling; SiC fibres; Weight functions

Crack resistance curve in glass matrix composite reinforced by long Nicalon (R) fibres - Dlouhy, Ivo; Kotoul, Michal; Vyslouzil, Tomas; Chlup, Zdenek; Boccaccini, Aldo R. (Journal of Materials Science, 2008)
Theoretical micromechanical analysis of bridged crack development at chevron-notch tip of three-point bend specimens has been applied to determine the crack resistance curve for a composite made of a glass matrix reinforced by continuous Nicalon® fibres. Fracture toughness (K IC) values were determined using the chevron-notch technique at room temperature. The theoretical predictions were based on micromechanical analysis exploiting weight functions. Detailed FEM analysis using the ANSYS package was applied to determine numerically the weight functions for orthotropic materials. Appropriate bridging models for the theoretical prediction of the R-curve behaviour typical of the investigated composite were applied together with the weight functions. Experimental observations confirmed the theoretical calculations. © 2008 Springer Science+Business Media, LLC.
UnivIS-Import:2015-03-09:Pub.2008.tech.IW.LM.crackr

Cross-linking of mesoporous bioactive glass nanoparticle incorporated gelatin hydrogels by tannic acid with enhanced mechanical performance and stability - Chen, Si; Li, Meng; Michálek, Martin; Kaňková, Hana; Zhao, Liang; Boccaccini, Aldo R.; Galusek, Dušan; Zheng, Kai (Materialia, 2024)
Gelatin-based hydrogels are used in diverse biomedical applications, such as wound dressings, tissue regeneration, and cell culture models. However, gelatin requires additional cross-linking to form a stable hydrogel. Tannic acid (TA), a polyphenolic compound, can undergo the Michael addition reaction and Schiff's base reaction with primary amine groups in neutral aqueous solutions. In this work, TA was selected as a cross-linker of gelatin to fabricate hydrogels reacting with primary amine groups in the gelatin molecular chain. Primary amine-modified mesoporous bioactive glass nanoparticles (AMBGNs) were added to further enhance the cross-linking of the system. The swelling ratios and weight losses showed that the most stable hydrogels retain approximately 53 % of their mass after 28 days of immersion in PBS solution. Young's modulus increased significantly with the increase in the content of TA and AMBGNs. The addition of TA and AMBGNs also resulted in a substantial reduction of gelation time. The prepared hydrogels possessed adequate stability and mechanical properties and showed potential for customized application in a variety of clinical service settings, such as wound healing, bone regeneration, and soft tissue regeneration.
CRIS-Team Scopus Importer:2024-07-12
Keywords: Bioactive glasses; Gelatin; Tannic acid

Crystallization and Melting Behavior of Poly(Butylene Succinate) Nanocomposites Containing Silica-Nanotubes and Strontium Hydroxyapatite Nanorods - Papageorgiou, George Z.; Papageorgiou, Dimitrios G.; Chrissafis, Konstantinos; Bikiaris, Dimitrios; Will, Julia; Hoppe, Alexander; Roether, Judith; Boccaccini, Aldo R. (Industrial & Engineering Chemistry Research, 2014)
The multiple melting behavior of poly(butylene succinate) (PBSu) nanocomposites containing silica nanotubes (SiNTs) and strontium hydroxyapatite nanorods (SrHNRs) was studied with Step Scan DSC. In the reversing signal curves, recrystallization proved to be significant for samples crystallized at low temperature, which lead to large supercooling, favoring fast crystallization and formation of poor crystals that suffer recrystallization on subsequent heating scans. The crystallization study, under both isothermal and nonisothermal conditions, evidenced that only SiNTs act effectively as nucleating agents. Consequently, crystallization of the nanocomposite samples filled with 5 and mainly with 20 wt % SiNTs occurred faster than that of the neat polymeric matrix. The insertion of SrHNRs slightly lowered the crystallization rate of PBSu due to the formation of larger aggregates inside the PBSu matrix, which may inhibit crystallization. The size of crystals was smaller for PBSu/SiNTs samples, as it was proved by wide angle X-ray diffracrion (WAXD), whereas the addition of SrHNRs did not significantly affect the crystalline size of nanocomposites. © 2013 American Chemical Society.
UnivIS-Import:2015-03-09:Pub.2014.tech.IW.LM.crysta

Crystallization study of sol–gel derived 13-93 bioactive glass powder - Nawaz, Qaisar; de Pablos-Martín, Araceli; Martins de Souza e Silva, Juliana; Berthold, Lutz; Hurle, Katrin; Contreras Jaimes, Altair T.; Sitarz, Maciej; Brauer, Delia S.; Boccaccini, Aldo R. (Journal of the European Ceramic Society, 2020)
Multicomponent silicate bioactive glass (BG) (53SiO2‐20CaO‐6Na2O‐4P2O5‐12K2O‐ 5MgO in wt. %) (13–93 composition) was prepared via the sol–gel process. The influence of thermal treatment on the crystallization was evaluated using differential scanning calorimetry (DSC), X-ray diffraction (XRD), transmission electron microscopy (TEM) and X-ray nano-computed tomography (nano-CT). The temperature and time of the thermal treatment strongly influenced the formation of the crystalline phases. The preliminary outcomes demonstrate the possibility of tailoring the crystallinity of 13–93 BG powder in the range 5–43 wt. % by controlling the temperature and time of the heat treatment. The microstructure of powders sintered at two different temperatures (650 °C and 700 °C from 30 min to 4 h) was evaluated by TEM. X-ray nano-computed tomography (nano-CT) was used to visualize the 3D morphology and distribution of crystallization areas in the samples in powder form. A large range between the glass transformation and the crystallization temperatures is observed, which provides the prospect of a suitable material to manufacture directly 3D structures (e.g. porous scaffolds) without an intermediate processing step.
CRIS-Team Scopus Importer:2020-10-16
Keywords: Bioactive glasses; Crystallization behavior; Rietveld refinement; Sintering of 13-93 bioactive glass; Sol–gel

CT-based non-destructive quantification of 3D-printed hydrogel implants - Steinert, Jule; Wittenberg, Thomas; Bednarzig, Vera; Detsch, Rainer; Claussen, Joelle; Gerth, Stefan (Informatik aktuell, 2020)
Additive manufacturing of hydrogel-based implants, as e.g for the human skull are becoming more important as they should allow a modelling of the different natural layers of the skullcap, and support the bone healing process. Nevertheless, the quality, structure and consistency of such 3D-printed hydrogel implants are important for the reliable production, quality assurance and further tests of the implant production. One possibility for non-destructive imaging and quantification of such additive manufactured hydrogels is computed tomography combined with quantitative image analysis. Hence, the goal of this work is the quantitative analysis of the hydrogel-air relationship as well as the automated computation of the hydrogel angles between the different hydrogel layers. This is done by application and evaluation of various classical image analysis methods such as thresholdig, morphological operators, region growing and Fourier transformation of the CT-slices. Results show, that the examined quantities (channels in the hydrogel lattice, angles between the layers) are in the expected ranges, and it can be concluded that the additive manufacturing process may yield usable hydrogel meshes for reconstructive medicine.
CRIS-Team Scopus Importer:2020-04-21

Cu/HA/ZnS/PEEK multicomponent coatings with varied copper content for biomedical applications - Kuśmierczyk, Filip; Moskalewicz, Tomasz; Grysakowski, Bartosz; Cieniek, Łukasz; Zimowski, Sławomir; Kopia, Agnieszka; Unalan, Irem; Boccaccini, Aldo R. (Surface & Coatings Technology, 2023)
In this study, multicomponent Cu/HA/ZnS/PEEK coatings were electrophoretically deposited (EPD) on Zr-2.5Nb alloy substrates. The kinetics of coating deposition from suspensions with various Cu contents was studied. Heating and slow cooling enabled the densification of coatings. The densified coatings were characterized by a limited number of pores and the presence of HA agglomerates on their surface. All of the obtained coatings exhibited significant roughness and mild hydrophilicity, as well as high adhesion to the alloy substrates. The coatings increased the electrochemical corrosion resistance of the zirconium alloy. The coating obtained from the suspension with the highest copper content exhibited high antibacterial properties for both bacteria strains after 24 h. However, after 72 h incubation, the samples had a better effect against Gram-negative than Gram-positive bacteria. Furthermore, this coating variant allowed the formation of hydroxyapatite on its surface in the Kokubo test. The obtained coatings showed antibacterial and bioactive properties with potential for further development, particularly as permanent coatings for bone implant applications.
CRIS-Team Scopus Importer:2023-10-27
Keywords: Antibacterial coating; Bioactive coating; Electrophoretic deposition; Sulfonated PEEK; Zirconium alloy

Curcumin-Containing Orthopedic Implant Coatings Deposited on Poly-Ether-Ether-Ketone/Bioactive Glass/Hexagonal Boron Nitride Layers by Electrophoretic Deposition - Virk, Ranjot; Ur Rehman, Muhammad Atiq; Munawar, Muhammad; Schubert, Dirk W.; Goldmann, Wolfgang; Dusza, Ján; Boccaccini, Aldo R. (Coatings, 2019)
Electrophoretic deposition (EPD) was used to produce a multilayer coatings system based on chitosan/curcumin coatings on poly-ether-ether-ketone (PEEK)/bioactive glass (BG)/hexagonal boron nitride (h-BN) layers (previously deposited by EPD on 316L stainless steel) to yield bioactive and antibacterial coatings intended for orthopedic implants. Initially, PEEK/BG/h-BN coatings developed on 316L stainless steel (SS) substrates were analyzed for wear studies. Then, the EPD of chitosan/curcumin was optimized on 316L SS for suspension stability, thickness, and homogeneity of the coatings. Subsequently, the optimized EPD parameters were applied to produce chitosan/curcumin coatings on the PEEK/BG/h-BN layers. The multilayered coatings produced by EPD were characterized in terms of composition, microstructure, drug release kinetics, antibacterial activity, and in vitro bioactivity. Scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR) confirmed the deposition of chitosan/curcumin on the multilayer coating system. The release of curcumin upon immersion of multilayer coatings in phosphate-buffered saline (PBS) was confirmed by ultraviolet/visible (UV/VIS) spectroscopic analysis. The antibacterial effect of chitosan/curcumin as the top coating was determined by turbidity tests (optical density measurements). Moreover, the multilayer coating system formed an apatite-like layer upon immersion in simulated body fluid (SBF), which is similar in composition to the hydroxyapatite component of bone, confirming the possibility of achieving close bonding between bone and the coating surface.
Keywords: curcumin; chitosan; bioactive coatings; electrophoretic deposition; antibacterial coatings

Cu-Releasing Bioactive Glass Coatings and Their in Vitro Properties - Rau, Julietta V.; Curcio, Mariangela; Raucci, Maria Grazia; Barbaro, Katia; Fasolino, Ines; Teghil, Roberto; Ambrosio, Luigi; De Bonis, Angela; Boccaccini, Aldo R. (ACS Applied Materials and Interfaces, 2019)
Bioactive glasses are well-known materials suitable for bone-related applications thanks to their biocompatibility and osteoconductivity. In order to improve their in vivo performance, the modification of the glass composition by adding ions with specific biological functions is required. As copper (Cu) possesses antibacterial properties, in this study, 5 wt % of CuO has been added to the 45S5 bioactive glass composition. The investigation of the effect of the Cu-containing bioactive glass on cellular behavior has revealed that the presence of Cu induces an early differentiation of human mesenchymal stem cells through osteoblast phenotype, Target la earn promotes the expression of anti-inflammatory interleukin, and reduces proinflammatory interleukin expression. With the aim to produce coatings with antibacterial properties, the Cu-containing bioactive glass was used as the target material for the pulsed laser deposition (PLD) of bioactive thin films. PLD experiments were carried out at different substrate temperatures to study the effect on the film's characteristics. All of the films are compact, crack-free, and characterized by a rough morphology and good wettability. The in vitro bioactivity was demonstrated by the apatite growth on the coating surface, after soaking in simulated body fluid, revealed by Raman spectroscopy and scanning electron microscopy-energy dispersive X-ray analyses. The antibacterial study proved that the material showed more effective activity against three Gram-negative bacteria (Pseudomonas aeruginosa, Escherichia coli, Salmonella enterica) rather than against Gram-positive bacteria (Staphylococcus aureus).
CRIS-Team WoS Importer:2019-03-06