14-3-3ε protein-immobilized PCL-HA electrospun scaffolds with enhanced osteogenicity - Rivero, G.; Aldana, A. A.; Frontini Lopez, Y. R.; Liverani, Liliana; Boccaccini, Aldo R.; Bustos, D. M.; Abraham, G. A. (Journal of Materials Science: Materials in Medicine, 2019)
Adipose-derived mesenchymal stem cells (ASCs) accelerate the osteointegration of bone grafts and improve the efficiency in the formation of uniform bone tissue, providing a practical and clinically attractive approach in bone tissue regeneration. In this work, the effect of nanofibrous biomimetic matrices composed of poly(ε-caprolactone) (PCL), nanometric hydroxyapatite (nHA) particles and 14-3-3 protein isoform epsilon on the initial stages of human ASCs (hASCs) osteogenic differentiation was investigated. The cells were characterized by flow cytometry and induction to differentiation to adipogenic and osteogenic lineages. The isolated hASCs were induced to differentiate to osteoblasts over all scaffolds, and adhesion and viability of the hASCs were found to be similar. However, the activity of alkaline phosphatase (ALP) as early osteogenic marker in the PCL-nHA/protein scaffold was four times higher than in PCL-nHA and more than five times than the measured in neat PCL. [Figure not available: see fulltext.].
CRIS-Team Scopus Importer:2019-09-03

14-3-3ε protein-loaded 3D hydrogels favor osteogenesis - Aldana, Ana A.; Uhart, Marina; Abraham, Gustavo A.; Bustos, Diego M.; Boccaccini, Aldo R. (Journal of Materials Science: Materials in Medicine, 2020)
3D printing has emerged as vanguard technique of biofabrication to assemble cells, biomaterials and biomolecules in a spatially controlled manner to reproduce native tissues. In this work, gelatin methacrylate (GelMA)/alginate hydrogel scaffolds were obtained by 3D printing and 14-3-3ε protein was encapsulated in the hydrogel to induce osteogenic differentiation of human adipose-derived mesenchymal stem cells (hASC). GelMA/alginate-based grid-like structures were printed and remained stable upon photo-crosslinking. The viscosity of alginate allowed to control the pore size and strand width. A higher viscosity of hydrogel ink enhanced the printing accuracy. Protein-loaded GelMA/alginate-based hydrogel showed a clear induction of the osteogenic differentiation of hASC cells. The results are relevant for future developments of GelMA/alginate for bone tissue engineering given the positive effect of 14-3-3ε protein on both cell adhesion and proliferation.
CRIS-Team Scopus Importer:2020-11-13

3D bioprinting of mouse pre-osteoblasts and human MSCs using bioinks consisting of gelatin and decellularized bone particles - Kara Özenler, Aylin; Distler, Thomas; Akkineni, Ashwini Rahul; Tihminlioglu, Funda; Gelinsky, Michael; Boccaccini, Aldo R. (Biofabrication, 2024)
One of the key challenges in biofabrication applications is to obtain bioinks that provide a balance between printability, shape fidelity, cell viability, and tissue maturation. Decellularization methods allow the extraction of natural extracellular matrix, preserving tissue-specific matrix proteins. However, the critical challenge in bone decellularization is to preserve both organic (collagen, proteoglycans) and inorganic components (hydroxyapatite) to maintain the natural composition and functionality of bone. Besides, there is a need to investigate the effects of decellularized bone (DB) particles as a tissue-based additive in bioink formulation to develop functional bioinks. Here we evaluated the effect of incorporating DB particles of different sizes (≤45 and ≤100 μm) and concentrations (1%, 5%, 10% (wt %)) into bioink formulations containing gelatin (GEL) and pre-osteoblasts (MC3T3-E1) or human mesenchymal stem cells (hTERT-MSCs). In addition, we propose a minimalistic bioink formulation using GEL, DB particles and cells with an easy preparation process resulting in a high cell viability. The printability properties of the inks were evaluated. Additionally, rheological properties were determined with shear thinning and thixotropy tests. The bioprinted constructs were cultured for 28 days. The viability, proliferation, and osteogenic differentiation capacity of cells were evaluated using biochemical assays and fluorescence microscopy. The incorporation of DB particles enhanced cell proliferation and osteogenic differentiation capacity which might be due to the natural collagen and hydroxyapatite content of DB particles. Alkaline phosphatase activity is increased significantly by using DB particles, notably, without an osteogenic induction of the cells. Moreover, fluorescence images display pronounced cell-material interaction and cell attachment inside the constructs. With these promising results, the present minimalistic bioink formulation is envisioned as a potential candidate for bone tissue engineering as a clinically translatable material with straightforward preparation and high cell activity.
CRIS-Team Scopus Importer:2024-03-22
Keywords: 3D bioprinting; bone tissue engineering; decellularized bone; gelatin; microbial transglutaminase

3D bioprinting of multifunctional alginate dialdehyde (ADA)–gelatin (GEL) (ADA-GEL) hydrogels incorporating ferulic acid - Bider, Faina; Miola, Marta; Clejanu, Corina Elena; Götzelmann, Johanna; Kuth, Sonja; Vernè, Enrica; Basu, Bikramjit; Boccaccini, Aldo R. (International Journal of Biological Macromolecules, 2024)
The present work explores the 3D extrusion printing of ferulic acid (FA)-containing alginate dialdehyde (ADA)–gelatin (GEL) scaffolds with a wide spectrum of biophysical and pharmacological properties. The tailored addition of FA (≤0.2 %) increases the crosslinking between FA and GEL in the presence of calcium chloride (CaCl2) and microbial transglutaminase, as confirmed using trinitrobenzenesulfonic acid (TNBS) assay. In agreement with an increase in crosslinking density, a higher viscosity of ADA-GEL with FA incorporation was achieved, leading to better printability. Importantly, FA release, enzymatic degradation and swelling were progressively reduced with an increase in FA loading to ADA-GEL, over 28 days. Similar positive impact on antibacterial properties with S. epidermidis strains as well as antioxidant properties were recorded. Intriguingly, FA incorporated ADA-GEL supported murine pre-osteoblast proliferation with reduced osteosarcoma cell proliferation over 7 days in culture, implicating potential anticancer property. Most importantly, FA-incorporated and cell-encapsulated ADA-GEL can be extrusion printed to shape fidelity-compliant multilayer scaffolds, which also support pre-osteoblast cells over 7 days in culture. Taken together, the present study has confirmed the significant potential of 3D bioprinting of ADA-GEL-FA ink to obtain structurally stable scaffolds with a broad spectrum of biophysical and therapeutically significant properties, for bone tissue engineering applications.
CRIS-Team Scopus Importer:2024-01-05
Keywords: 3D bioprinting; Alginate; Phytotherapeutic agents

3D Bioprinting of Multifunctional Dynamic Nanocomposite Bioinks Incorporating Cu-Doped Mesoporous Bioactive Glass Nanoparticles for Bone Tissue Engineering - Zhu, Hui; Monavari, Mahshid; Zheng, Kai; Distler, Thomas; Ouyang, Liliang; Heid, Susanne; Jin, Zhaorui; He, Jiankang; Li, Dichen; Boccaccini, Aldo R. (Small, 2022)
Bioprinting has seen significant progress in recent years for the fabrication of bionic tissues with high complexity. However, it remains challenging to develop cell-laden bioinks exhibiting superior physiochemical properties and bio-functionality. In this study, a multifunctional nanocomposite bioink is developed based on amine-functionalized copper (Cu)-doped mesoporous bioactive glass nanoparticles (ACuMBGNs) and a hydrogel formulation relying on dynamic covalent chemistry composed of alginate dialdehyde (oxidized alginate) and gelatin, with favorable rheological properties, improved shape fidelity, and structural stability for extrusion-based bioprinting. The reversible dynamic microenvironment in combination with the impact of cell-adhesive ligands introduced by aminated particles enables the rapid spreading (within 3 days) and high survival (>90%) of embedded human osteosarcoma cells and immortalized mouse bone marrow-derived stroma cells. Osteogenic differentiation of primary mouse bone marrow stromal stem cells (BMSCs) and angiogenesis are promoted in the bioprinted alginate dialdehyde-gelatin (ADA-GEL or AG)-ACuMBGN scaffolds without additional growth factors in vitro, which is likely due to ion stimulation from the incorporated nanoparticles and possibly due to cell mechanosensing in the dynamic matrix. In conclusion, it is envisioned that these nanocomposite bioinks can serve as promising platforms for bioprinting complex 3D matrix environments providing superior physiochemical and biological performance for bone tissue engineering.
CRIS-Team Scopus Importer:2022-02-11

3D hydrogel-based microcapsules as an in vitro model to study tumorigenicity, cell migration and drug resistance. - Ertekin, Özlem; Monavari, Mahshid; Krüger, René; Fuentes Chandia, Miguel Angel; Parma, Beatrice; Letort, Gaelle; Tripal, Philipp; Boccaccini, Aldo R.; Boßerhoff, Anja Katrin; Ceppi, Paolo; Kappelmann-Fenzl, Melanie; Leal-Egaña, Aldo (Acta Biomaterialia, 2022)
In this work, we analyzed the reliability of alginate-gelatin microcapsules as artificial tumor model. These tumor-like scaffolds are characterized by their composition and stiffness (∼25 kPa), and their capability to restrict -but not hinder- cell migration, proliferation and release from confinement. Hydrogel-based microcapsules were initially utilized to detect differences in mechano-sensitivity between MCF7 and MDA-MB-231 breast cancer cells, and the endothelial cell line EA.hy926. Additionally, we used RNA-seq and transcriptomic methods to determine how the culture strategy (i.e. 2D v/s 3D) may pre-set the expression of genes involved in multidrug resistance, being then validated by performing cytotoxicological tests and assays of cell morphology. Our results show that both breast cancer cells can generate elongated multicellular spheroids inside the microcapsules, prior being released (mimicking intravasation stages), a behavior which was not observed in endothelial cells. Further, we demonstrate that cells isolated from 3D scaffolds show resistance to cisplatin, a process which seems to be strongly influenced by mechanical stress, instead of hypoxia. We finally discuss the role played by aneuploidy in malignancy and resistance to anticancer drugs, based on the increased number of polynucleated cells found within these microcapsules. Overall, our outcomes demonstrate that alginate-gelatin microcapsules represent a simple, yet very accurate tumor-like model, enabling us to mimic the most relevant malignant hints described in vivo, suggesting that confinement and mechanical stress need to be considered when studying pathogenicity and drug resistance of cancer cells in vitro. STATEMENT OF SIGNIFICANCE: In this work, we analyzed the reliability of alginate-gelatin microcapsules as an artificial tumor model. These scaffolds are characterized by their composition, elastic properties, and their ability to restrict cell migration, proliferation, and release from confinement. Our results demonstrate four novel outcomes: (i) studying cell migration and proliferation in 3D enabled discrimination between malignant and non-pathogenic cells, (ii) studying the cell morphology of cancer aggregates entrapped in alginate-gelatin microcapsules enabled determination of malignancy degree in vitro, (iii) determination that confinement and mechanical stress, instead of hypoxia, are required to generate clones resistant to anticancer drugs (i.e. cisplatin), and (iv) evidence that resistance to anticancer drugs could be due to the presence of polynucleated cells localized inside polymer-based artificial tumors.

3D Microcontact Printing for Combined Chemical and Topographical Patterning on Porous Cell Culture Membrane. - Borowiec, Justyna; Hampl, Joerg; Singh, Sukhdeep; Haefner, Sebastian; Friedel, Karin; Mai, Patrick; Brauer, Dana; Ruther, Florian; Liverani, Liliana; Boccaccini, Aldo R.; Schober, Andreas (ACS Applied Materials and Interfaces, 2018)
Micrometer-scale biochemical or topographical patterning is commonly used to guide the cell attachment and growth, but the ability to combine these patterns into an integrated surface with defined chemical and geometrical characteristics still remains a technical challenge. Here, we present a technical solution for simultaneous construction of 3D morphologies, in the form of channels, on porous membranes along with precise transfer of extracellular matrix proteins into the channels to create patterns with geometrically restricting features. By combining the advantages of microthermoforming and microcontact printing, this technique offers a unique patterning process that provides spatiotemporal control over morphological and chemical feature in a single step. By use of our 3D-microcontact printing (3DμCP), determined microstructures like channels with different depths and widths even with more complex patterns can be fabricated. Collagen, fibronectin, and laminin were successfully transferred inside the predesigned geometries, and the validity of the process was confirmed by antibody staining. Cells cultivated on 3DμCP patterned polycarbonate membrane have shown selective adhesion and growth. This technique offers a novel tool for creating freeform combinatorial patterning on the thermoformable surface.

3D printed gelatin/decellularized bone composite scaffolds for bone tissue engineering: Fabrication, characterization and cytocompatibility study - Kara, Aylin; Distler, Thomas; Polley, Christian; Schneidereit, Dominik; Seitz, Hermann; Friedrich, Oliver; Tihminlioglu, Funda; Boccaccini, Aldo R. (Materials Today Bio, 2022)
Three-dimensional (3D) printing technology enables the design of personalized scaffolds with tunable pore size and composition. Combining decellularization and 3D printing techniques provides the opportunity to fabricate scaffolds with high potential to mimic native tissue. The aim of this study is to produce novel decellularized bone extracellular matrix (dbECM)-reinforced composite-scaffold that can be used as a biomaterial for bone tissue engineering. Decellularized bone particles (dbPTs, 100 mu m diameter) were obtained from rabbit femur and used as a reinforcement agent by mixing with gelatin (GEL) in different concentrations. 3D scaffolds were fabricated by using an extrusion-based bioprinter and crosslinking with microbial transglutaminase (mTG) enzyme, followed by freeze-drying to obtain porous structures. Fabricated 3D scaffolds were characterized morphologically, mechanically, and chemically. Furthermore, MC3T3-E1 mouse pre-osteoblast cells were seeded on the dbPTs reinforced GEL scaffolds (GEL/dbPTs) and cultured for 21 days to assess cytocompatibility and cell attachment. We demonstrate the 3D-printability of dbPTs-reinforced GEL hydrogels and the achievement of homogenous distribution of the dbPTs in the whole scaffold structure, as well as bioactivity and cytocompatibility of GEL/dbPTs scaffolds. It was shown that Young's modulus and degradation rate of scaffolds were enhanced with increasing dbPTs content. Multiphoton microscopy imaging displayed the interaction of cells with dbPTs, indicating attachment and proliferation of cells around the particles as well as into the GEL-particle hydrogels. Our results demonstrate that GEL/dbPTs hydrogel formulations have potential for bone tissue engineering.
CRIS-Team WoS Importer:2022-07-15

3D-Printed Multifunctional Hydrogels with Phytotherapeutic Properties: Development of Essential Oil-Incorporated ALG-XAN Hydrogels for Wound Healing Applications - Ünalan, Irem; Schrüfer, Stefan; Schubert, Dirk W.; Boccaccini, Aldo R. (ACS Biomaterials Science and Engineering, 2023)
This study aimed to develop three-dimensional (3D)-printed hydrogels containing phytotherapeutic agents as multifunctional wound dressings. In this regard, 3D-printed sodium alginate (ALG)-xanthan gum (XAN) hydrogels incorporated with different clove essential oil (CLV) concentrations were produced by the extrusion-based 3D-printing technology. Rheology measurements, filament fusion, and filament collapse analyses indicated that XAN’s blending overcame the challenges associated with ALG’s printability and shape fidelity. Attenuated total reflection-Fourier-transform infrared (ATR-FTIR) spectra and total phenolic content assay confirmed the presence of CLV in the 3D-printed hydrogels. Additionally, the releasing profile showed that CLV exhibited long-term release for up to 28 days. Furthermore, the incorporation of CLV increased 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging while reducing the S. aureus and E. coli relative bacterial viability; thereby, the CLV incorporation enhanced the 3D-printed ALG-XAN hydrogel antioxidant and antibacterial activity. In addition, anti-inflammatory activity was assessed using Raw 264.7 macrophage-like cells, and the results demonstrated that CLV reduced nitric oxide (NO) concentration in medium, indicating a potential anti-inflammatory effect. Moreover, in vitro cytotoxicity results showed that the incorporation of CLV has no toxic effect on NHDF cells, whereas the proliferation of NHDF cells exhibited a dose-dependent response. In conclusion, the present study shows not only the development of a new ALG-XAN biomaterial ink but also the potential benefit of natural phytotherapeutics incorporated into 3D-printed hydrogels as a multifunctional wound dressing.
CRIS-Team Scopus Importer:2023-07-21
Keywords: 3D printing; essential oils; hydrogels; phytotherapeutic agents; sodium alginate; wound healing; xanthan gum

3D printed oxidized alginate-gelatin bioink provides guidance for C2C12 muscle precursor cell orientation and differentiation via shear stress during bioprinting - Distler, Thomas; Solisito, Aditya; Schneidereit, Dominik; Friedrich, Oliver; Detsch, Rainer; Boccaccini, Aldo R. (Biofabrication, 2020)
Biofabrication can be a tool to three-dimensionally (3D) print muscle cells embedded inside hydrogel biomaterials, ultimately aiming to mimic the complexity of the native muscle tissue and to createin-vitromuscle analogues for advanced repair therapies and drug testing. However, to 3D print muscle analogues of high cell alignment and synchronous contraction, the effect of biofabrication process parameters on myoblast growth has to be understood. A suitable biomaterial matrix is required to provide 3D printability as well as matrix degradation to create space for cell proliferation, matrix remodelling capacity, and cell differentiation. We demonstrate that by the proper selection of nozzle size and extrusion pressure, the shear stress during extrusion-bioprinting of mouse myoblast cells (C2C12) can achieve cell orientation when using oxidized alginate-gelatin (ADA-GEL) hydrogel bionk. The cells grow in the direction of printing, migrate to the hydrogel surface over time, and differentiate into ordered myotube segments in areas of high cell density. Together, our results show that ADA-GEL hydrogel can be a simple and cost-efficient biodegradable bioink that allows the successful 3D bioprinting and cultivation of C2C12 cellsin-vitroto study muscle engineering.
Keywords: myoblasts; muscle tissue engineering; 3D printing; oxidized alginate; gelatin; hydrogel

3D printed poly(hydroxybutyrate-co-hydroxyvalerate)-45S5 bioactive glass composite resorbable scaffolds suitable for bone regeneration - Araoz, Beatriz; Karakaya, Emine; Gonzalez Wusener, Ana; Detsch, Rainer; Bizzotto, Juan; Gueron, Geraldine; Boccaccini, Aldo R.; Hermida, Elida B. (Journal of Materials Research, 2021)
3D printing for tissue engineering requires biomaterials with mechanical and biological properties suitable for both tissue regeneration and the printing process. A filament made of poly(hydroxybutyrate-co-hydroxyvalerate) (PHBV) combined with 45S5 Bioglass (BG) was used to print 3D scaffolds by fused deposition modeling (FDM). Chemical treatment of BG particles with chlorotrimethylsilane (CTMS) improved the ductility of the extruded filaments and allowed excellent printability. Controlling the printing parameter infill density (I-%), from 20 to 90%, scaffolds were obtained with interconnected pores and channel sizes in the 100-800 mu m range and exhibiting tensile modulus from 0.25 to 1.36 GPa. PHBV + BG scaffolds and PHBV scaffolds coated with CTMS treated BG particles, as a model of a rough and biologically active coating, showed no cytotoxic effects, and cells preferred the scaffolds containing BG in terms of cell spreading. Mechanical and biological properties of the scaffolds were similar to those of the extracellular matrix (ECM) of trabecular bone.
CRIS-Team WoS Importer:2021-07-16

3D-printed β-TCP/S53P4 bioactive glass scaffolds coated with tea tree oil: Coating optimization, in vitro bioactivity and antibacterial properties - Alves, Ana Paula Nogueira; Arango Ospina, Marcela; Oliveira, Rodrigo Luiz Moraes Saldanha; Ferreira, Igor Maia; de Moraes, Elisângela Guzi; Hartmann, Malte; de Oliveira, Antônio Pedro Novaes; Boccaccini, Aldo R.; de Sousa Trichês, Eliandra (Journal of Biomedical Materials Research Part B: Applied Biomaterials, 2022)
Bone infection treatment is a significant challenge for the orthopedic field. 3D printing is a promising technology to produce scaffolds with customized architecture, able to stimulate and support bone growth. β-TCP and S53P4 bioactive glass (BG) are well-known biomaterials for scaffold manufacturing. However, a multifunctional scaffold, able to inhibit microbial proliferation at the defect site, is of increasing interest to avoid infection recurrence. Tea tree oil (TTO) has aroused interest as an antimicrobial agent to minimize the use of antibiotics. Therefore, combining the regenerative potential of a bioceramic with TTO's antimicrobial properties could result in a scaffold capable of stimulating tissue growth and treating infections. In this context, this study aimed to produce and characterize 3D-printed β-TCP/S53P4 BG scaffolds coated with TTO. Scaffolds morphological and chemical characterizations were carried out through XDR, SEM, and FTIR analysis. β-TCP/S53P4 BG scaffolds showed a compressive strength of 2 MPa and 53 ± 2% of porosity. The scaffolds were coated by two different procedures, using an ethanol/TTO (EtOH/TTO) and a gelatin/TTO (Gel/TTO) solution with 5, 10, and 15% (v/v) TTO. The addition of TTO decreased MG-63 cell viability for both coating groups, but the Gel/TTO group showed higher cell viability. The antibacterial activity of the coated scaffolds was evaluated against S. aureus and higher inhibition of colony formation was found for Gel/TTO group. Therefore, the coating with Gel/TTO was effective in terms of antibacterial activity and cell viability. Such Gel/TTO coated β-TCP/S53P4 BG scaffolds are proposed for antibacterial bone tissue engineering.
CRIS-Team Scopus Importer:2022-12-16
Keywords: 3D printing; antibacterial activity; S53P4 bioactive glass; scaffolds; tea tree oil; β-Tricalcium phosphate

3D printing and characterization of human nasoseptal chondrocytes laden dual crosslinked oxidized alginate-gelatin hydrogels for cartilage repair approaches - Schwarz, Silke; Kuth, Sonja; Distler, Thomas; Gögele, Clemens; Stölzel, Katharina; Detsch, Rainer; Boccaccini, Aldo R.; Schulze-Tanzil, Gundula (Materials Science and Engineering C, 2020)
As cartilage is one of the few tissues in the human body that is not vascularized, the body has very limited capabilities to repair cartilage defects. Hence, novel condro-instructive biomaterials facilitating cartilage formation by implanted chondrocytes are required. In this work, an oxidized alginate-gelatin hydrogel system, alginate-di-aldehyde (ADA) and gelatin (GEL), was used to fabricate 3D printed grid-like structures for cartilage tissue engineering. Enzymatic and ionic crosslinking techniques using microbial transglutaminase (mTG) and divalent ions (CaCl2) were combined to ensure long-term stability of the 3D printed structures. Human nasoseptal chondrocytes were embedded in ADA-GEL prior to 3D printing. Cell viability, proliferation, and metabolic activity were analyzed after 7 and 14 days. The influence of the enzymatic crosslinking and the 3D printing process on the primary human chondrocytes were investigated. It was found that neither the 3D printing process nor the crosslinking by mTG impaired chondrocyte viability. The formation of the main cartilage-specific extracellular matrix components collagen type II and cartilage proteoglycans was shown by immunohistochemical staining. The combination of enzymatic and ionic crosslinking for the 3D printing of ADA-GEL hydrogels is therefore a promising approach for the 3D cultivation of primary human chondrocytes for cartilage tissue engineering.
CRIS-Team Scopus Importer:2020-07-10
Keywords: Alginate di-aldehyde (ADA); Bioprinting; Cartilage; Human nasoseptal chondrocytes; Hydrogel; Microbial transglutaminase

3D printing of alginate dialdehyde-gelatin (ADA-GEL) hydrogels incorporating phytotherapeutic icariin loaded mesoporous SiO2-CaO nanoparticles for bone tissue engineering - Monavari, Mahshid; Homaeigohar, Shahin; Fuentes Chandia, Miguel Angel; Nawaz, Qaisar; Monavari, Mehran; Venkatraman, Arvind; Boccaccini, Aldo R. (Materials Science and Engineering C, 2021)
3D printing enables a better control over the microstructure of bone restoring constructs, addresses the challenges seen in the preparation of patient-specific bone scaffolds, and overcomes the bottlenecks that can appear in delivering drugs/growth factors promoting bone regeneration. Here, 3D printing is employed for the fabrication of an osteogenic construct made of hydrogel nanocomposites. Alginate dialdehyde-gelatin (ADA-GEL) hydrogel is reinforced by the incorporation of bioactive glass nanoparticles, i.e. mesoporous silica-calcia nanoparticles (MSNs), in two types of drug (icariin) loading. The composites hydrogel is printed as superhydrated composite constructs in a grid structure. The MSNs not only improve the mechanical stiffness of the constructs but also induce formation of an apatite layer when the construct is immersed in simulated body fluid (SBF), thereby promoting cell adhesion and proliferation. The nanocomposite constructs can hold and deliver icariin efficiently, regardless of its incorporation mode, either as loaded into the MSNs or freely distributed within the hydrogel. Biocompatibility tests showed that the hydrogel nanocomposites assure enhanced osteoblast proliferation, adhesion, and differentiation. Such optimum biological properties stem from the superior biocompatibility of ADA-GEL, the bioactivity of the MSNs, and the supportive effect of icariin in relation to cell proliferation and differentiation. Taken together, given the achieved structural and biological properties and effective drug delivery capability, the hydrogel nanocomposites show promising potential for bone tissue engineering.
CRIS-Team Scopus Importer:2021-10-29
Keywords: 3D printed hydrogel; ADA-GEL; Bone tissue engineering; Drug delivery; Mesoporous SiO; Phytotherapeutic agent

3D printing of biomedical materials and devices - Bandyopadhyay, Amit; Ghosh, Sourabh; Boccaccini, Aldo R.; Bosenaff, Susmita (Journal of Materials Research, 2021)
3D printing, or additive manufacturing, is a transformative technology platform impacting various disciplines, including biomaterials and biomedical devices. We present scientists, engineers, and medical professionals' perspectives about 3D printing of biomaterials and biomedical devices in this special issue. This issue is geared towards understanding the structure–process–property relationships involving different materials in vitro, in vivo, and in silico environments. The focus issue covers polymer, ceramic, glass, metallic and composite biomaterials involving various 3D-printing processes such as fused deposition, powder bed fusion, Bioprinting, directed energy deposition, and binder jetting; addressing research topics including tissue engineering, drug delivery, porous metal implants, bioink development, cell–materials interactions, wear degradation, nano-bio materials, and challenges in point-of-care delivery. Such diversity of research topics is an accurate representation of what is happening in this field globally. This article presents some of the success stories, challenges, and future directions in the 3D printing of biomaterials and devices. Graphic abstract: [Figure not available: see fulltext.]
CRIS-Team Scopus Importer:2021-11-05
Keywords: 3D printing; Additive manufacturing; Biomaterial; Biomedical

3D printing of bioreactors in tissue engineering: A generalised approach - Gensler, Marius; Leikeim, Anna; Möllmann, Marc; Komma, Miriam; Heid, Susanne; Müller, Claudia; Boccaccini, Aldo R.; Salehi, Sahar; Groeber-Becker, Florian; Hansmann, Jan (PLoS ONE, 2020)
3D printing is a rapidly evolving field for biological (bioprinting) and non-biological applications. Due to a high degree of freedom for geometrical parameters in 3D printing, prototype printing of bioreactors is a promising approach in the field of Tissue Engineering. The variety of printers, materials, printing parameters and device settings is difficult to overview both for beginners as well as for most professionals. In order to address this problem, we designed a guidance including test bodies to elucidate the real printing performance for a given printer system. Therefore, performance parameters such as accuracy or mechanical stability of the test bodies are systematically analysed. Moreover, post processing steps such as sterilisation or cleaning are considered in the test procedure. The guidance presented here is also applicable to optimise the printer settings for a given printer device. As proof of concept, we compared fused filament fabrication, stereolithography and selective laser sintering as the three most used printing methods. We determined fused filament fabrication printing as the most economical solution, while stereolithography is most accurate and features the highest surface quality. Finally, we tested the applicability of our guidance by identifying a printer solution to manufacture a complex bioreactor for a perfused tissue construct. Due to its design, the manufacture via subtractive mechanical methods would be 21-fold more expensive than additive manufacturing and therefore, would result in three times the number of parts to be assembled subsequently. Using this bioreactor we showed a successful 14-day-culture of a biofabricated collagen-based tissue construct containing human dermal fibroblasts as the stromal part and a perfusable central channel with human microvascular endothelial cells. Our study indicates how the full potential of biofabrication can be exploited, as most printed tissues exhibit individual shapes and require storage under physiological conditions, after the bioprinting process.
CRIS-Team Scopus Importer:2020-12-11

3D printing of electrically conductive hydrogels for tissue engineering and biosensors – A review - Distler, Thomas; Boccaccini, Aldo R. (Acta Biomaterialia, 2019)
Electrically conductive biomaterials are gaining increasing interest owing to their potential to be used in smart, biosensoric and functional tissue-engineered scaffolds and implants. In combination with 3D printing technology, this class of materials might be one of the most advanced approaches towards future medical implants regarding potential functionalities and design possibilities. Conductive hydrogels themselves have been researched for potential sensoric and tissue engineering applications for more than a decade, while the 3D printing of such functional materials is still under early exploration. This review aims to provide a short insight into the most recent developments of 3D printable and electrically conductive hydrogels. It also provides a summary of the last few years of research in this field, with key scope on 3D printing for biomedical applications. The final literature search was conducted in May 2019, with the specific keywords ‘3D’, ‘printing’, ‘conductive’, ‘hydrogel’, ‘biocompatible’ and combinations of the latter, using advanced search in the databases Scopus®, Web of Science® (Web of Knowledge®) and Google Scholar®. A total of 491 results were gained, while 19 recent publications were identified with the above-mentioned criteria and keywords, which are the studies finally discussed in the paper. The key results have been summarised, and the remaining challenges in the field and the scope for future research activities have been discussed. Statement of Significance: Hydrogels are among the most frequently used biomaterials in tissue engineering (TE). A new class of hydrogels, namely, electrically conductive hydrogels (ECHs), has been introduced in recent years. Although ECHs have been comprehensively reviewed in the literature, the combination of ECHs with 3D printing technology has emerged only recently, representing a promising key development toward the fabrication of functional 3D TE constructs. In this review, we cover for the first time the state of the art in the field of 3D printing of ECHs. Previous advances are presented, reviewing the 3D printing technologies utilised, spatial resolution and electrical conductivity values achieved, in addition to discussing the obtained mechanical properties and emerging applications of these materials.
CRIS-Team Scopus Importer:2019-09-27
Keywords: 3D printing; Advanced tissue engineering strategies; Bioplotting; Biosensors; Conductive hydrogels; Electrically conductive polymers; Smart biomaterials

3D Printing of Mechanically Resistant Poly (Glycerol Sebacate) (PGS)-Zein Scaffolds for Potential Cardiac Tissue Engineering Applications - Ruther, Florian; Roether, Judith; Boccaccini, Aldo R. (Advanced Engineering Materials, 2022)
Due to the limited regenerative capacity of the natural human myocardium, 3D printing of the cyclic polyester poly (glycerol sebacate) (PGS) offers a promising alternative to produce scaffolds (cardiac patches) for cardiac tissue engineering. Since the 3D printability and subsequent thermal crosslinking of pure PGS without any modification or additives are challenging, a PGS-zein-salt-based printing process is developed in this work by mixing PGS pre-polymer with ground and sieved sodium chloride particles and additionally with different amounts of the corn protein zein. The resulting inks show excellent printability and high shape fidelity both during the printing process and after thermal crosslinking. Chemical analysis indicates the successful integration of zein into the PGS backbone. Mechanical characterization shows the anisotropic behavior of the structure in the alternating printing direction. Subsequent biological assessments reveal no cytotoxic effects on C2C12 cells, rendering the developed PGS-zein combination a suitable material for 3D printing of cardiac patches.
CRIS-Team Scopus Importer:2022-04-15
Keywords: 3D printing; cardiac tissue engineering; poly (glycerol sebacate); self-regulating properties; zein

3D printing of piezoelectric and bioactive barium titanate-bioactive glass scaffolds for bone tissue engineering - Polley, Christian; Distler, Thomas; Scheufler, Caroline; Detsch, Rainer; Lund, Henrik; Springer, Armin; Schneidereit, Dominik; Friedrich, Oliver; Boccaccini, Aldo R.; Seitz, Hermann (Materials Today Bio, 2023)
Bone healing is a complex process orchestrated by various factors, such as mechanical, chemical and electrical cues. Creating synthetic biomaterials that combine several of these factors leading to tailored and controlled tissue regeneration, is the goal of scientists worldwide. Among those factors is piezoelectricity which creates a physiological electrical microenvironment that plays an important role in stimulating bone cells and fostering bone regeneration. However, only a limited number of studies have addressed the potential of combining piezoelectric biomaterials with state-of-the-art fabrication methods to fabricate tailored scaffolds for bone tissue engineering. Here, we present an approach that takes advantage of modern additive manufacturing techniques to create macroporous biomaterial scaffolds based on a piezoelectric and bioactive ceramic-crystallised glass composite. Using binder jetting, scaffolds made of barium titanate and 45S5 bioactive glass are fabricated and extensively characterised with respect to their physical and functional properties. The 3D-printed ceramic-crystallised glass composite scaffolds show both suitable mechanical strength and bioactive behaviour, as represented by the accumulation of bone-like calcium phosphate on the surface. Piezoelectric scaffolds that mimic or even surpass bone with piezoelectric constants ranging from 1 to 21 pC/N are achieved, depending on the composition of the composite. Using MC3T3-E1 osteoblast precursor cells, the scaffolds show high cytocompatibility coupled with cell attachment and proliferation, rendering the barium titanate/45S5 ceramic-crystallised glass composites promising candidates for bone tissue engineering.
CRIS-Team Scopus Importer:2023-07-28
Keywords: 3D printing; Barium titanate; Bioactivity; Bone regeneration; Piezoelectricity

3D printing of piezoelectric barium titanate-hydroxyapatite scaffiolds with interconnected porosity for bone tissue engineering - Polley, Christian; Distler, Thomas; Detsch, Rainer; Lund, Henrik; Springer, Armin; Boccaccini, Aldo R.; Seitz, Hermann (Materials, 2020)
The prevalence of large bone defects is still a major problem in surgical clinics. It is, thus, not a surprise that bone-related research, especially in the field of bone tissue engineering, is a major issue in medical research. Researchers worldwide are searching for the missing link in engineering bone graft materials that mimic bones, and foster osteogenesis and bone remodeling. One approach is the combination of additive manufacturing technology with smart and additionally electrically active biomaterials. In this study, we performed a three-dimensional (3D) printing process to fabricate piezoelectric, porous barium titanate (BaTiO3) and hydroxyapatite (HA) composite scaffiolds. The printed scaffiolds indicate good cytocompatibility and cell attachment as well as bone mimicking piezoelectric properties with a piezoelectric constant of 3 pC/N. This work represents a promising first approach to creating an implant material with improved bone regenerating potential, in combination with an interconnected porous network and a microporosity, known to enhance bone growth and vascularization.
CRIS-Team Scopus Importer:2020-05-22
Keywords: 3D printing; Barium titanate; Bioceramic; Biomaterial; Bone; Piezoelectric

3D Spheroids Versus 3D Tumor-Like Microcapsules: Confinement and Mechanical Stress May Lead to the Expression of Malignant Responses in Cancer Cells - Fuentes-Chandía, Miguel; Vierling, Andreas; Kappelmann-Fenzl, Melanie; Monavari, Mahshid; Letort, Gaelle; Höne, Lucas; Parma, Beatrice; Antara, Sharmin Khan; Ertekin, Özlem; Palmisano, Ralf; Dong, Meng; Böpple, Kathrin; et al. (Advanced Biology, 2021)
As 2D surfaces fail to resemble the tumoral milieu, current discussions are focused on which 3D cell culture strategy may better lead the cells to express in vitro most of the malignant hints described in vivo. In this study, this question is assessed by analyzing the full genetic profile of MCF7 cells cultured either as 3D spheroids-considered as “gold standard” for in vitro cancer research- or immobilized in 3D tumor-like microcapsules, by RNA-Seq and transcriptomic methods, allowing to discriminate at big-data scale, which in vitro strategy can better resemble most of the malignant features described in neoplastic diseases. The results clearly show that mechanical stress, rather than 3D morphology only, stimulates most of the biological processes involved in cancer pathogenicity, such as cytoskeletal organization, migration, and stemness. Furthermore, cells entrapped in hydrogel-based scaffolds are likely expressing other physiological hints described in malignancy, such as the upregulated expression of metalloproteinases or the resistance to anticancer drugs, among others. According to the knowledge, this study represents the first attempt to answer which 3D experimental system can better mimic the neoplastic architecture in vitro, emphasizing the relevance of confinement in cancer pathogenicity, which can be easily achieved by using hydrogel-based matrices.
CRIS-Team Scopus Importer:2021-05-28
Keywords: 3D cancer models; 3D cell culture; biomaterials for cancer research; solid stress; tumor-like microcapsules

45S5 bioactive glass-based scaffolds coated with cellulose nanowhiskers for bone tissue engineering - Li, Wei; Garmendia, Nere; De Larraya, Uxua Perez; Ding, Yaping; Detsch, Rainer; Gruenewald, Alina; Roether, Judith; Schubert, Dirk W.; Boccaccini, Aldo R. (RSC Advances, 2014)
Highly porous 45S5 bioactive glass-based scaffolds prepared by foam replication method were coated with cellulose nanowhiskers by dip coating method. The obtained cellulose nanowhisker-coated scaffolds retained the high porosity and interconnected pore structure. The cellulose coating improved the mechanical properties of the scaffolds and did not hinder their bioactivity in simulated body fluid. In vitro biocompatibility assessment was carried out by qualitative evaluation of the morphology of osteoblast-like cells (MG-63) seeded onto the scaffolds. The cells were shown to attach and spread on both uncoated scaffolds and cellulose nanowhisker-coated scaffolds, thus cellulose nanowhisker coating seems to have no negative influence on the behavior of MG-63 cells. The obtained bioactive and biocompatible composite scaffolds represent promising candidates for bone tissue engineering applications.

45S5 bioactive glass coatings by atmospheric plasma spraying obtained from feedstocks prepared by different routes - Lopez Calvo, Veronica; Vicent Cabedo, Monica; Bannier, Emilie; Canas Recacha, Eugeni; Boccaccini, Aldo R.; Cordero Arias, Luis Eduardo; Sanchez Vilches, Enrique (Journal of Materials Science, 2014)
45S5 bioactive glass powders with the composition of 45 SiO, 6 PO, 24.5 CaO and 24.5 wt% NaO were melted and quenched in water to obtain a frit. The frit was milled using two different routes: dry milling followed by sieving to obtain glass particles and wet milling followed by spray drying to obtain a powder comprising porous agglomerates. All feedstocks showed adequate characteristics that make them suitable to be deposited by atmospheric plasma spraying. The powders and coatings were characterised by field-emission gun environmental scanning electron microscope and X-ray diffraction. The roughness and the contact angle of the coatings were also determined. The bioactivity of the powders and coatings was assessed by immersion in simulated body fluid. It was found that bioactive glass prepared from bioglass frit by dry milling exhibited similar bioactivity as that of a commercial bioactive glass. All coatings produced showed good adhesion to the substrate as well as suitable surface properties to ensure efficient contact with body fluid. Regardless of the characteristics of the feedstocks or plasma spray conditions used, all coatings were exclusively made up of an amorphous phase. On the other hand, micrographs revealed that the characteristics of the feedstock strongly impact on the final coating microstructure. The most homogeneous microstructure was obtained when the feedstock was prepared by fine dry grinding of the frit. For this coating, the formation of a bioactive layer was also proved by Fourier transform infrared spectroscopy and X-ray diffraction.

45S5 bioactive glass reactivity by dynamic vapour sorption - Naseri, Shiva; Lepry, William C.; Li, Wei; Waters, Kristian E.; Boccaccini, Aldo R.; Nazhat, Showan N. (Journal of Non-Crystalline Solids, 2016)
Reactivity in an aqueous medium is a key parameter for determining the potential bioactivity (i.e., the ability to form a bond to bone) of bioactive and soluble glasses. In this study, dynamic vapour sorption (DVS), a gravimetric technique that measures vapour sorption under controlled relative humidity (RH) and temperature, was used to investigate the short-term aqueous interactions of Bioglass® 45S5 (BG). Specifically, DVS was applied to monitor the sorption characteristics of BG particles of three different sizes exposed to variable RH between 0 and 90%. In addition, the effect of directly exposing these glasses to 90% RH for up to 24 h and its effect on the structural and morphological properties was analysed. Attributable to their larger surface areas, smaller BG particles adsorbed more vapour, and consequently underwent larger total and final mass percent changes as well as greater extent of surface transformation. Precise vapour sorption rates, determined using DVS, were correlated with BG particle surface area and initial rate of ion release when immersed in deionized water, thus demonstrating the ability of DVS to accurately predict reactivity and potential bioactivity.
Keywords: Bioactive glass; Bioactivity; Bioglass; DVS (dynamic vapour sorption); Solubility

45S5-Bioglass®-Based 3D-Scaffolds Seeded with Human Adipose Tissue-Derived Stem Cells Induce In Vivo Vascularization in the CAM Angiogenesis Assay - Handel, Marina; Hammer, Timo R.; Nooeaid, Patcharakamon; Boccaccini, Aldo R.; Höfer, Dirk (Tissue Engineering - Part A, 2013)
Poor vascularization is the key limitation for long-term acceptance of large three-dimensional (3D) tissue engineering constructs in regenerative medicine. 45S5 Bioglass® was investigated given its potential for applications in bone engineering. Since native Bioglass® shows insufficient angiogenic properties, we used a collagen coating, to seed human adipose tissue-derived stem cells (hASC) confluently onto 3D 45S5 Bioglass ®-based scaffolds. To investigate vascularization by semiquantitative analyses, these biofunctionalized scaffolds were then subjected to in vitro human umbilical vein endothelial cells formation assays, and were also investigated in the chorioallantoic membrane (CAM) angiogenesis model, an in vivo angiogenesis assay, which uses the CAM of the hen's egg. In their native, nonbiofunctionalized state, neither Bioglass®-based nor biologically inert fibrous polypropylene control scaffolds showed angiogenic properties. However, significant vascularization was induced by hASC-seeded scaffolds (Bioglass® and polypropylene) in the CAM angiogenesis assay. Biofunctionalized scaffolds also showed enhanced tube lengths, compared to unmodified scaffolds or constructs seeded with fibroblasts. In case of biologically inert hernia meshes, the quantification of vascular endothelial growth factor secretion as the key angiogenic stimulus strongly correlated to the tube lengths and vessel numbers in all models. This correlation proved the CAM angiogenesis assay to be a suitable semiquantitative tool to characterize angiogenic effects of larger 3D implants. In addition, our results suggest that combinations of suitable scaffold materials, such as 45S5 Bioglass ®, with hASC could be a promising approach for future tissue engineering applications. © 2013 Mary Ann Liebert, Inc.
UnivIS-Import:2015-03-09:Pub.2013.tech.IW.LM.45s5bi_6

45S5Bioglass®-based scaffolds coated with selenium nanoparticles or with poly(lactide-co-glycolide)/selenium particles: Processing, evaluation and antibacterial activity - Stevanovic, Magdalena; Filipovic, Nenad; Djurdjevic, Jelena; Lukic, Miodrag; Milenkovic, Marina; Boccaccini, Aldo R. (Colloids and Surfaces B-Biointerfaces, 2015)
In the bone tissue engineering field, there is a growing interest in the application of bioactive glass scaffolds (45S5Bioglass®) due to their bone bonding ability, osteoconductivity and osteoinductivity. However, such scaffolds still lack some of the required functionalities to enable the successful formation of new bone, e.g. effective antibacterial properties. A large number of studies suggest that selenium (Se) has significant role in antioxidant protection, enhanced immune surveillance and modulation of cell proliferation. Selenium nanoparticles (SeNp) have also been reported to possess antibacterial as well as antiviral activities. In this investigation, uniform, stable, amorphous SeNp have been synthesized and additionally immobilized within spherical PLGA particles (PLGA/SeNp). These particles were used to coat bioactive glass-based scaffolds synthesized by the foam replica method. Samples were characterized by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDS) and transmission electron microscopy (TEM). SeNp, 45S5Bioglass®/SeNp and 45S5Bioglass®/PLGA/SeNp showed a considerable antibacterial activity against Gram positive bacteria, Staphylococcus aureus and Staphylococcus epidermidis, one of the main causative agents of orthopedic infections. The functionalized Se-coated bioactive glass scaffolds represent a new family of bioactive, antibacterial scaffolds for bone tissue engineering applications.
Keywords: Scaffold; Bioglass; Selenium nanoparticles; PLGA; Antibacterial activity

45S5 Bioglass® concentrations modulate the release of vancomycin hydrochloride from gelatin–starch films: evaluation of antibacterial and cytotoxic effects - Rivadeneira, Josefina; Laura Di Virgilio, Ana; Carina Audisio, M.; Boccaccini, Aldo R.; Gorustovich, Alejandro A. (Journal of Materials Science, 2017)

45S5 Bioglass®-derived scaffolds coated with organic-inorganic hybrids containing graphene - Fabbri, Paola; Valentini, Luca; Hum, Jasmin; Detsch, Rainer; Boccaccini, Aldo R. (Materials Science and Engineering C, 2013)
Highly porous 45S5 Bioglass®-based scaffolds fabricated by a foam replication technique were coated with electrically conductive organic-inorganic hybrid layers containing graphene by a solution method. α,ω- Triethoxysilane terminated poly (ethylene glycol) and tetraethoxysilane were used as the precursors of the organic-inorganic hybrid coatings, that contained 1.5 wt.% of homogeneously dispersed graphene nanoplatelets. The resulting coated scaffolds retained their original high porosity and interconnected pore structure after coating. The presence of graphene did not impair the bioactivity of the scaffolds in simulated body fluid. Initial tests carried out using MG-63 cells demonstrated that both uncoated scaffolds and scaffolds coated with organic/inorganic hybrids containing graphene offered the cultured cells an adequate surface for cell attachment, spreading and expression of extracellular matrix. The results showed that scaffolds coated with graphene are biocompatible and they can support cellular activity. The electrical conductivity introduced by the coating might have the potential to increase tissue growth when cell culture is carried out under an applied electric field. © 2013 Elsevier B.V.
UnivIS-Import:2015-03-09:Pub.2013.tech.IW.LM.45s5bi
Keywords: 45S5 Bioglass®; Cell ingrowth; Graphene; Organic-inorganic hybrid coatings; Scaffolds

45S5 Bioglass®–MWCNT composite: processing and bioactivity - Porwal, Harshit; Estili, Mehdi; Grünewald, Alina; Grasso, Salvatore; Detsch, Rainer; Hu, Chunfeng; Sakka, Yoshio; Boccaccini, Aldo R.; Reece, Mike J. (Journal of Materials Science: Materials in Medicine, 2015)
Multi-walled carbon nanotube (MWCNT)–Bioglass (BG) matrix composite was fabricated using a facile and scalable aqueous colloidal processing method without using any surfactants followed by spark plasma sintering (SPS) consolidation. The individual MWCNTs were initially uniformly dispersed in water and then entirely immobilized on the BG particles during the colloidal processing, avoiding their common re-agglomeration during the water-removal and drying step, which guaranteed their uniform dispersion within the dense BG matrix after the consolidation process. SPS was used as a fast sintering technique to minimise any damage to the MWCNT structure during the high-temperature consolidation process. The electrical conductivity of BG increased by 8 orders of magnitude with the addition of 6.35 wt% of MWCNTs compared to pure BG. Short-duration tests were used in the present study as a preliminary evaluation to understand the effect of incorporating MWCNTs on osteoblast-like cells. The analysed cell proliferation, viability and phenotype expression of MG-63 cells showed inhibition on 45S5 Bioglass®–MWCNT composite surfaces.

4D Biofabrication of fibrous artificial nerve graft for neuron regeneration - Apsite, Indra; Constante, Gissela; Dulle, Martin; Vogt, Lena; Caspari, Anja; Boccaccini, Aldo R.; Synytska, Alla; Salehi, Sahar; Ionov, Leonid (Biofabrication, 2020)
In this paper, we describe the application of the 4D biofabrication approach for the fabrication of artificial nerve graft. Bilayer scaffolds consisting of uniaxially aligned polycaprolactone-poly(glycerol sebacate) (PCL-PGS) and randomly aligned methacrylated hyaluronic acid (HA-MA) fibers were fabricated using electrospinning and further used for the culture of PC-12 neuron cells. Tubular structures form instantly after immersion of fibrous bilayer in an aqueous buffer and the diameter of obtained tubes can be controlled by changing bilayer parameters such as the thickness of each layer, overall bilayer thickness, and medium counterion concentration. Designed scaffolds showed a self-folded scroll-like structure with high stability after four weeks of real-time degradation. The significance of this research is in the fabrication of tuneable tubular nerve guide conduits that can simplify the current existing clinical treatment of neural injuries.
CRIS-Team Scopus Importer:2020-07-31
Keywords: 4D biofabrication; electrospinning; nerve guide conduits; neuron cells; self-folding

4D Biofabrication of T-Shaped Vascular Bifurcation - Kitana, Waseem; Apsite, Indra; Hazur, Jonas; Boccaccini, Aldo R.; Ionov, Leonid (Advanced Materials Technologies, 2022)
4D Biofabrication – a pioneering biofabrication technique – involves the automated fabrication of 3D constructs that are dynamic and show shape-transformation capability. Although current 4D biofabrication methods are highly promising for the fabrication of vascular elements such as tubes, the fabrication of tubular junctions is still highly challenging. Here, for the first time, a 4D biofabrication-based concept for the fabrication of a T-shaped vascular bifurcation using 3D printed shape-changing layers based on a mathematical model is reported. The formation of tubular structures with various diameters is achieved by precisely controlling the parameters (e.g. crosslinking time). Consequently, the 3D printed films show self-transformation into a T-junction upon immersion in water with a diameter of a few millimeters. Perfusion of the tubular T-junction with an aqueous medium simulating blood flow through vessels shows minimal leakages with a maximum flow velocity of 0.11 m s–1. Furthermore, human umbilical vein endothelial cells seeded on the inner surface of the plain T-junction show outstanding growth properties and excellent cell viability. The achieved diameters are comparable to the native blood vessels, which is still a challenge in 3D biofabrication. This approach paves the way for the fabrication of fully automatic self-actuated vascular bifurcations as vascular grafts.
CRIS-Team Scopus Importer:2022-10-21
Keywords: 3D printing; 4D biofabrication; ADA-Gel; blood vasculature; vascular bifurcation

A 3D Printed Bone Tissue Engineering Scaffold Composed of Alginate Dialdehyde-Gelatine Reinforced by Lysozyme Loaded Cerium Doped Mesoporous Silica-Calcia Nanoparticles - Monavari, Mahshid; Medhekar, Rucha Shirish; Nawaz, Qaisar; Monavari, Mehran; Fuentes Chandia, Miguel Angel; Homaeigohar, Shahin; Boccaccini, Aldo R. (Macromolecular Bioscience, 2022)
A novel biomaterial comprising alginate dialdehyde-gelatine (ADA-GEL) hydrogel augmented by lysozyme loaded mesoporous cerium doped silica-calcia nanoparticles (Lys-Ce-MSNs) is 3D printed to create bioactive scaffolds. Lys-Ce-MSNs raise the mechanical stiffness of the hydrogel composite scaffold and induce surface apatite mineralization, when the scaffold is immersed in simulated body fluid (SBF). Moreover, the scaffolds can co-deliver bone healing (Ca and Si) and antioxidant ions (Ce), and Lys to achieve antibacterial (and potentially anticancer) properties. The nanocomposite hydrogel scaffolds can hold and deliver Lys steadily. Based on the in vitro results, the hydrogel nanocomposite containing Lys assured improved pre-osteoblast cell (MC3T3-E1) proliferation, adhesion, and differentiation, thanks to the biocompatibility of ADA-GEL, bioactivity of Ce-MSNs, and the stabilizing effect of Lys on the scaffold structure. On the other hand, the proliferation level of MG63 osteosarcoma cells decreased, likely due to the effect of Lys. Last but not least, cooperatively, alongside gentamicin (GEN), Lys brought about a proper antibacterial efficiency to the hydrogel nanocomposite scaffold against gram-positive and gram-negative bacteria. Taken together, ADA-GEL/Lys-Ce-MSN nanocomposite holds great promise for 3D printing of multifunctional hydrogel bone tissue engineering (BTE) scaffolds, able to induce bone regeneration, address infection, and potentially inhibit tumor formation and growth.
CRIS-Team WoS Importer:2022-07-29

A 3D-Printed Wound-Healing Material Composed of Alginate Dialdehyde-Gelatin Incorporating Astaxanthin and Borate Bioactive Glass Microparticles - Monavari, Mahshid; Homaeigohar, Shahin; Medhekar, Rucha Shirish; Nawaz, Qaisar; Monavari, Mehran; Zheng, Kai; Boccaccini, Aldo R. (ACS Applied Materials and Interfaces, 2023)
In this study, a wound dressing composed of an alginate dialdehyde-gelatin (ADA-GEL) hydrogel incorporated by astaxanthin (ASX) and 70B (70:30 B2O3/CaO in mol %) borate bioactive glass (BBG) microparticles was developed through 3D printing. ASX and BBG particles stiffened the composite hydrogel construct and delayed its in vitro degradation compared to the pristine hydrogel construct, mainly due to their cross-linking role, likely arising from hydrogen bonding between the ASX/BBG particles and ADA-GEL chains. Additionally, the composite hydrogel construct could hold and deliver ASX steadily. The composite hydrogel constructs codelivered biologically active ions (Ca and B) and ASX, which should lead to a faster, more effective wound-healing process. As shown through in vitro tests, the ASXcontaining composite hydrogel promoted fibroblast (NIH 3T3) cell adhesion, proliferation, and vascular endothelial growth factor expression, as well as keratinocyte (HaCaT) migration, thanks to the antioxidant activity of ASX, the release of cell-supportive Ca2+ and B3+ ions, and the biocompatibility of ADA-GEL. Taken together, the results show that the ADA-GEL/BBG/ASX composite is an attractive biomaterial to develop multipurposed wound-healing constructs through 3D printing.
CRIS-Team WoS Importer:2023-06-02
Keywords: 3D printing; drug delivery; borate bioactive glass; astaxanthin. wound healing

A biomimetic approach for enhancing adhesion and osteogenic differentiation of adipose-derived stem cells on poly(butylene succinate) composites with bioactive ceramics and glasses - Nerantzaki, Maria; Koliakou, Iro; Kaloyianni, Martha G.; Koumentakou, Ioanna; Siska, Evangelia; Diamanti, Eleftheria; Karakassides, Michael A.; Boccaccini, Aldo R.; Bikiaris, Dimitrios N. (European Polymer Journal, 2017)
Keywords: Bioceramics; Biomimetic; Nanoparticles; Polymeric composites

Accelerated bioactive behavior of Nagelschmidtite bioceramics: Mimicking the nano and microstructural aspects of biological mineralization - Rincón-López, July Andrea; Hermann-Muñoz, Jennifer Andrea; Cinca-Luis, Núria; Fernández-Benavides, David Andrés; García-Cano, Irene; Guilemany-Casadamon, Jose Maria; Boccaccini, Aldo R.; Muñoz-Saldaña, Juan; Alvarado-Orozco, Juan Manuel (Journal of the European Ceramic Society, 2021)
The ability of the Nagelschmidtite (Nagel) phase to promote osteogenesis, cementogenesis, and angiogenesis increased the interest in using this calcium silicophosphate bioceramic for tissue regeneration and vascularization applications. Nagel phase is a solid solution with the general formula Ca7-xNax(PO4)2+x(SiO4)2-x, which allows several substitutions being Ca7(PO4)2(SiO4)2 the most reported stoichiometry. Inspired by the well-known 45S5 bioactive glass chemical composition, we developed a synthesis route to obtain a Na-rich Nagel single phase. The effect of this bioceramic chemical and structural properties on apatite formation and crystallization mechanism is reported. The structural aspects at the nano and microscale of the mechanism of apatite growth and crystallization from the Nagel phase were compared to the formation process of Extra-Cellular Matrix (ECM) deposits in biological systems, revealing a biomimetic behavior during the apatite biomineralization process from the bioceramic.
CRIS-Team Scopus Importer:2021-09-10
Keywords: Apatite biomimetics; Biomineralization; Nagelschmidtite; TEM

Accelerated Degradation Behavior and Cytocompatibility of Pure Iron Treated with Sandblasting - Zhou, Juncen; Yang, Yuyun; Alonso Frank, Micael; Detsch, Rainer; Boccaccini, Aldo R.; Virtanen, Sannakaisa (ACS Applied Materials and Interfaces, 2016)
Fe-based materials are of interest for use in biodegradable implants. However, their corrosion rate in the biological environment may be too slow for the targeted applications. In this work, sandblasting is applied as a successful surface treatment for increasing the degradation rate of pure iron in simulated body fluid. Two sandblasting surfaces with different roughness present various surface morphologies but similar degradation products. Electrochemistry tests revealed that sandblasted samples have a higher corrosion rate compared to that of bare iron, and even more noteworthy, the degradation rate of sandblasted samples remains significantly higher during long-term immersion tests. On the basis of our experimental results, the most plausible reasons behind the fast degradation rate are the special properties of sandblasted surfaces, including the change of surface composition (for the early stage), high roughness (occluded surface sites), and high density of dislocations. Furthermore, the cytocompatibility was studied on sandblasting surfaces using human osteoblast-like cells (MG-63) by indirect and direct contact methods. Results revealed that sandblasting treatment brings no adverse effect to the growth of MG-63 cells. This work demonstrates the significant potential of sandblasting for controlling the degradation behavior of iron-based materials for biomedical applications

Accelerated mineralization of dense collagen-nano bioactive glass hybrid gels incereases scaffold stiffness and regulates osteoblastic function - Marelli, Benedetto; Ghezzi, Chiara E.; Mohn, Dirk; Stark, Wendelin J.; Barralet, Jake E.; Boccaccini, Aldo R.; Nazhat, Showan N. (Biomaterials, 2011)
UnivIS-Import:2015-03-09:Pub.2011.tech.IW.LM.accele

AC electrophoretic deposition of organic-inorganic composite coatings - Yoshioka, T.; Chavez-Valdez, Alejandra; Roether, Judith; Schubert, Dirk W.; Boccaccini, Aldo R. (Journal of Colloid and Interface Science, 2013)
Alternating current electrophoretic deposition (AC-EPD) of polyacrylic acid (PAA)-titanium oxide (TiO2) nanoparticle composites on stainless steel electrodes was investigated in basic aqueous solution. AC square wave with duty cycle of 80% was applied at a frequency of 1kHz. FTIR-ATR spectra showed that both AC and direct current (DC) EPD successfully deposited PAA-TiO2 composites. The deposition rate using AC-EPD was lower than that obtained in direct current DC-EPD. However, the microstructure and surface morphology of the deposited composite coatings were different depending on the type of electric field applied. AC-EPD applied for not more than 5min led to smooth films without bubble formation, while DC-EPD for 1min or more showed deposits with microstructural defects possibly as result of water electrolysis. AC-EPD was thus for the first time demonstrated to be a suitable technique to deposit organic-inorganic composite coatings from aqueous suspensions, showing that applying a square wave and frequency of 1kHz leads to uniform PAA-TiO2 composite coatings on conductive materials. © 2012 Elsevier Inc.
UnivIS-Import:2015-03-09:Pub.2013.tech.IW.LM.acelec
Keywords: Alternating current (AC); Coatings; Composites; Electrophoretic deposition (EPD); Nanoparticles; Polyacrylic acid (PAA); Titanium oxide (TiO

acellular bioactivity of sol-gel derived borate glass-polycaprolactone electrospun scaffolds - Lepry, William C.; Smith, Sophia; Liverani, Liliana; Boccaccini, Aldo R.; Nazhat, Showan N. (Biomedical Glasses, 2016)
Recently, sol-gel derived borate glasses (BGs) have shown unprecedented conversion rates to bone-like mineral (hydroxycarbonated apatite). In an effort to explore their potential applications in bone tissue engineering, this study reports on the fabrication and characterization of BG particle incorporated electrospun "- polycaprolactone (PCL) fibrous composites. The electrospinning technique successfully incorporated PCL fibres with BG particles at 2.5 and 5 w/v%, with the higher BG loading creating a three-dimensional cotton-wool like morphology. Dynamic vapour sorption showed greater extents of mass change with BG content attributable to water sorption, and indicating greater reactivity in the composite systems. In vitro bioactivity was investigated in simulated body fluid for up to 7 days. Scanning electron microscopy, Fourier-transform infrared spectroscopy and x-ray diffraction indicated apatite formation in the 5 w/v% incorporated composite scaffold, which initiated as early as day 3. In summary, sol-gel derived BGs incorporated-fibrous electrospun PCL composites indicate rapid reactivity and bioactivity with potential applications in mineralized tissue engineering.
CRIS-Team Scopus Importer:2022-08-05
Keywords: Bioactivity; Borate glass; Electrospinning; Mineralization; PCL; Scaffolds

A comparative analysis of the cytocompatibility, protein adsorption, osteogenic and angiogenic properties of the 45S5- and S53P4-bioactive glass compositions - Westhauser, Fabian; Arango Ospina, Marcela; Hupa, Leena; Renkawitz, Tobias; Boccaccini, Aldo R.; Kunisch, Elke (Biomedical Materials, 2024)
Despite their long history of application in orthopedics, the osteogenic and angiogenic properties as well as the cytocompatibility and protein adsorption of the 45S5- (in wt%: 45.0 SiO2, 24.5 Na2O, 24.5 CaO, 6.0 P2O5) and S53P4- (in wt%: 53.0 SiO2, 23.0 Na2O, 20.0 CaO, 4.0 P2O5) bioactive glass (BG) compositions have not yet been directly compared in one and the same experimental setting. In this study, the influence of morphologically equal granules of both BGs on proliferation, viability, osteogenic differentiation and angiogenic response of human bone-marrow-derived mesenchymal stromal cells (BMSCs) was assessed. Furthermore, their impact on vascular tube formation and adsorption of relevant proteins was evaluated. Both BGs showed excellent cytocompatibility and stimulated osteogenic differentiation of BMSCs. The 45S5-BG showed enhanced stimulation of bone morphogenic protein 2 (BMP2) gene expression and protein production compared to S53P4-BG. While gene expression and protein production of vascular endothelial growth factor (VEGF) were stimulated, both BGs had only limited influence on tubular network formation. 45S5-BG adsorbed a higher portion of proteins, namely BMP2 and VEGF, on its surface. In conclusion, both BGs show favorable properties with slight advantages for 45S5-BG. Since protein adsorption on BG surfaces is important for their biological performance, the composition of the proteome formed by osteogenic cells cultured on BGs should be analyzed in order to gain a deeper understanding of the mechanisms that are responsible for BG-mediated stimulation of osteogenic differentiation.
CRIS-Team Scopus Importer:2024-02-23
Keywords: 45S5-bioactive glass; angiogenesis; bioactive glass; cytocompatibility; osteogenesis; protein adsorption; S53P4-bioactive glass

A comparative in vitro and in vivo analysis of the biological properties of the 45S5-, 1393-, and 0106-B1-bioactive glass compositions using human bone marrow-derived stromal cells and a rodent critical size femoral defect model - Kunisch, Elke; Fiehn, Linn Anna; Saur, Merve; Arango Ospina, Marcela; Merle, Christian; Hagmann, Sébastien; Stiller, Adrian; Hupa, Leena; Renkawitz, Tobias; Boccaccini, Aldo R.; Westhauser, Fabian (Biomaterials Advances, 2023)
Since the introduction of the 45S5-bioactive glass (BG), numerous new BG compositions have been developed. Compared to the 45S5-BG, 1393-BG shows favorable processing properties due to its low crystallization tendency and the 1393-BG-based borosilicate 0106-B1-BG exhibits improved angiogenic properties due to its boron content. Despite their close (chemical) relationship, the biological properties of the mentioned BG composition have not yet been comparatively examined. In this study, the effects of the BGs on proliferation, viability, osteogenic differentiation, and angiogenic factor production of human bone marrow-derived mesenchymal stromal cells were assessed. Scaffolds made of the BGs were introduced in a critical-sized femur defect model in rats in order to analyze their impact on bone defect regeneration. In vitro, 1393-BG and 0106-B1-BG outperformed 45S5-BG with regard to cell proliferation and viability. 1393-BG enhanced osteogenic differentiation; 0106-B1-BG promoted angiogenic factor production. In vivo, 0106-B1-BG and 45S5-BG outperformed 1393-BG in terms of angiogenic and osteoclastic response resulting in improved bone regeneration. In conclusion, the biological properties of BGs can be significantly modified by tuning their composition. Demonstrating favorable processing properties and an equally strong in vivo bone regeneration potential as 45S5-BG, 0106-B1-BG qualifies as a basis to incorporate other bioactive ions to improve its biological properties.
CRIS-Team Scopus Importer:2023-07-07
Keywords: Angiogenesis; Bioactive glass; Biomaterials; Bone defect regeneration; Mesenchymal stromal cells; Osteogenesis

A comparative study of oxygen diffusion in tissue engineering scaffolds - Fiedler, T.; Belova, I. V.; Murch, G. E.; Poologasundarampillai, G.; Jones, J. R.; Roether, Judith; Boccaccini, Aldo R. (Journal of Materials Science: Materials in Medicine, 2014)
Tissue engineering scaffolds are designed to support tissue self-healing within physiological environments by promoting the attachment, growth and differentiation of relevant cells. Newly formed tissue must be supplied with sufficient levels of oxygen to prevent necrosis. Oxygen diffusion is the major transport mechanism before vascularization is completed and oxygen is predominantly supplied via blood vessels. The present study compares different designs for scaffolds in the context of their oxygen diffusion ability. In all cases, oxygen diffusion is confined to the scaffold pores that are assumed to be completely occupied by newly formed tissue. The solid phase of the scaffolds acts as diffusion barrier that locally inhibits oxygen diffusion, i.e. no oxygen passes through the scaffold material. As a result, the oxygen diffusivity is determined by the scaffold porosity and pore architecture. Lattice Monte Carlo simulations are performed to compare the normalized oxygen diffusivities in scaffolds obtained by the foam replication (FR) method, robocasting and sol-gel foaming. Scaffolds made by the FR method were found to have the highest oxygen diffusivity due to their high porosity and interconnected pores. These structures enable the best oxygen supply for newly formed tissue among the scaffold types considered according to the present numerical predictions.

A comparative study of the effects of different bioactive fillers in PLGA matrix composites and their suitability as bone substitute materials: A thermo-mechanical and in vitro investigation - Simpson, R. L.; Nazhat, S. N.; Blaker, J. J.; Bismarck, A.; Hill, R.; Boccaccini, Aldo R.; Hansen, U. N.; Amis, A. A. (Journal of the Mechanical Behavior of Biomedical Materials, 2015)
Bone substitute composite materials with poly(L-lactide-co-glycolide) (PLGA) matrices and four different bioactive fillers: CaCO3, hydroxyapatite (HA), 4555 Bioglass (R) (45S5 BG), and ICIE4 bioactive glass (a lower sodium glass than 45S5 BG) were produced via melt blending, extrusion and moulding. The viscoelastic, mechanical and thermal properties, and the molecular weight of the matrix were measured. Thermogravimetric analysis evaluated the effect of filler composition on the thermal degradation of the matrix. Bioactive glasses caused premature degradation of the matrix during processing, whereas CaCO3 or HA did not. All composites, except those with 4555 BG, had similar mechanical strength and were stiffer than PLGA alone in compression, whilst all had a lower tensile strength. Dynamic mechanical analysis demonstrated an increased storage modulus (E') in the composites (other than the 45S5 BG filled PLGA). The effect of water uptake and early degradation was investigated by short-term in vitro aging in simulated body fluid, which indicated enhanced water uptake over the neat polymer; bioactive glass had the greatest water uptake, causing matrix plasticization. These results enable a direct comparison between bioactive filler type in poly(alpha-hydroxyester) composites, and have implications when selecting a composite material for eventual application in bone substitution. (C) 2015 Elsevier Ltd. All rights reserved.
Keywords: Bioactive glass; Hydroxyapatite; Poly(alpha-hydroxyester); Bone substitute; Composite

A critical review on polydopamine surface-modified scaffolds in musculoskeletal regeneration - Tolabi, Hamidreza; Bakhtiary, Negar; Sayadi, Shaghayegh; Tamaddon, Maryam; Ghorbani, Farnaz; Boccaccini, Aldo R.; Liu, Chaozong (Frontiers in Bioengineering and Biotechnology, 2022)
Increasing concern about age-related diseases, particularly musculoskeletal injuries and orthopedic conditions, highlights the need for strategies such as tissue engineering to address them. Surface modification has been developed to create pro-healing interfaces, personalize scaffolds and provide novel medicines. Polydopamine, a mussel-inspired adhesive polymer with highly reactive functional groups that adhere to nearly all substrates, has gained attention in surface modification strategies for biomaterials. Polydopamine was primarily developed to modify surfaces, but its effectiveness has opened up promising approaches for further applications in bioengineering as carriers and nanoparticles. This review focuses on the recent discoveries of the role of polydopamine as a surface coating material, with focus on the properties that make it suitable for tackling musculoskeletal disorders. We report the evolution of using it in research, and discuss papers involving the progress of this field. The current research on the role of polydopamine in bone, cartilage, muscle, nerve, and tendon regeneration is discussed, thus giving comprehensive overview about the function of polydopamine both in-vitro and in-vivo. Finally, the report concludes presenting the critical challenges that must be addressed for the clinical translation of this biomaterial while exploring future perspectives and research opportunities in this area.
CRIS-Team Scopus Importer:2022-12-16
Keywords: musculoskeletal tissue; polydopamine; scaffolds; surface engineering; tissue engineering

Actively brazed alumina to alumina joints using CuTi, CuZr and eutectic AgCuTi filler alloys - Jasim, K. Mohammed; Hashim, F. A.; Yousif, R. H.; Rawlings, R. D.; Boccaccini, Aldo R. (Ceramics International, 2010)
Al2O3 to Al2O3 joints were produced using a one stage active brazing technique based on CuTi, CuZr and AgCuTi active brazing alloys. Single- and double-butt joints were used for microstructural (light and scanning electron microscopy and X-ray diffraction) and mechanical property (double shear test) studies, respectively. The joints produced with CuZr filler alloys (containing 2%, 4%, 6% and 8% Zr, wt%) showed low shear strengths (0.2-0.4 MPa) due to the presence of ZrO2 at the braze-substrate interface and failed in mode I crack opening. Higher shear strengths of 15-24 and 42 MPa were obtained by using CuTi filler alloys (containing 2%, 4%, 6%, 8% and 10% Ti, wt%) (mode II/mode III dependent on the Ti content) and the eutectic (Ag-27 wt% Cu-5 wt% Ti) alloy, respectively. The high shear strengths were attributed to the small amount of Cu 2(AlTi)4O at the braze-substrate interface and led, in the case of the ternary alloy, to the failure of the substrate rather than the braze (mode III axial splitting). © 2010 Elsevier Ltd and Techna Group S.r.l. All rights reserved.
UnivIS-Import:2015-03-09:Pub.2010.tech.IW.LM.active
Keywords: AgCuTi; Alumina; Brazing; CuTi; CuZr; Double shear strength; Fracture modes

AC vs. DC Electrophoretic Deposition of Hydroxyapatite on Titanium - Kollath, V. Ozhukil; Chen, Qiang; Closset, R.; Luyten, J.; Traina, K.; Mullens, S.; Boccaccini, Aldo R.; Cloots, R. (Journal of the European Ceramic Society, 2013)
In this study, electrophoretic deposition (EPD) of hydroxyapatite (HA) powder on titanium plate was performed using butanol as solvent under direct current (DC) and alternating current (AC) fields. The zeta potential of the suspensions was measured to define their stability and the charge on the particles. Coating thickness was varied by adjusting the voltage and time of deposition. Surface morphology and cross section thickness were studied using scanning electron microscopy and image analysis software. Surface crack density was calculated from the micrographs. The results showed that the samples of similar thickness have higher grain density when coated using AC as compared to DC EPD. This facile but novel test proves the capability of AC-EPD to attain denser and uniform HA coatings from non-aqueous medium. © 2013 Elsevier Ltd.
UnivIS-Import:2015-03-09:Pub.2013.tech.IW.LM.acvsdc
Keywords: Alternating current; Biomedical coatings; Electrophoretic deposition; Hydroxyapatite; Titanium

Additive manufacturing of bioactive glasses and silicate bioceramics - Gmeiner, R.; Deisinger, Ulrike; Schönherr, J.; Lechner, B.; Detsch, Rainer; Boccaccini, Aldo R.; Stampfl, J. (Journal of Ceramic Science and Technology, 2015)
This paper reviews the application of a broad range of additive manufacturing technologies (AMTs), including Stereolithographic Ceramic Manufacturing (SLCM/LCM), 3D-Printing, indirect and direct Selective Laser Sintering/Melting (SLS/SLM), Dispense Plotting and Inkjet Plotting on bioactive glasses (BGs) and silicate bioceramics to fabricate a variety of dense and porous structures for biomedical applications (e.g. bone replacement materials). Topical studies in the literature are complemented by recent data of the authors' own work, highlighting the state of the art of additive bioceramic production. The specific characteristics of the technologies used, their advantages and disadvantages and the scope for future research in this field are discussed. To date, many studies focus on 45S5 Bioglass® due to its broad commercial availability. However, other bioactive glass formulations and sol-gel derived BGs are being also considered in the context of AMTs. As the geometrical accuracy and mechanical properties of the fabricated parts strongly vary among the different AMTs, in-depth knowledge of the detailed capabilities of each production process targeted for BGs and other silicate bioceramic materials, as collated in this review, provides information on the basic requirements and challenges for establishing follow-up studies and for possible expansion of the application fields of such additive-manufactured structures.
Keywords: Additive manufacturing; Bioactive glasses; Scaffolds; Silicate bioceramics

Additive manufacturing of cell-loaded alginate enriched with alkaline phosphatase for bone tissue engineering application - Detsch, Rainer; Sarker, Bapi; Zehnder, Tobias; Boccaccini, Aldo R.; Douglas, Timothy E.L. (BioNanoMaterials, 2014)
Hydrogels are gaining interest as scaffolds for bone tissue regeneration due to ease of incorporation of cells and biological molecules such as enzymes. Mineralization of hydrogels, desirable for bone tissue regeneration applications, may be achieved enzymatically by incorporation of alkaline phosphatase (ALP). Additive manufacturing techniques such as bioplotting enable the layer-by-layer creation of three-dimensional hydrogel scaffolds with highly defined geometry and internal architecture. In this study, we present a novel method to produce macroporous hydrogel scaffolds in combination with cell-loaded capsule-containing struts by 3D bioplotting. This approach enables loading of the capsules and strut phases with different cells and/or bioactive substances and hence makes compartmentalization within a scaffold possible. 3D porous alginate scaffolds enriched with ALP and MG-63 osteoblast-like cells were produced by bioplotting struts of alginate which were loaded with pre-fabricated alginate capsules. Two combinations were compared, namely ALP in the struts and cells in the capsules and vice-versa. Both combinations were cytocompatible for cells and mineralization of scaffolds could be detected in both cases, according to an OsteoImage staining. ALP had no adverse effect on cytocompatibility and enhanced mitochondrial activity.
Keywords: Additive manufacturing; Alginate hydrogel; Bone tissue engineering; Cytocompatibility; Enzyme

Adhesion and interfacial characterization of biomimetically texturized lithium disilicate - Zorzin, José Ignacio; Beck, Simon; Belli, Renan; Petschelt, Anselm; Boccaccini, Aldo R.; Lohbauer, Ulrich (International Journal of Adhesion and Adhesives, 2019)
Lithium disilicate glass-ceramic (LS2) can be biomimetically textured by crystal orientation, mimicking the microstructure of dental enamel and inducing anisotropic mechanical responses to crack growth. The deliberate texturization of LS2 plays to the clinical advantage of reinforcing weak sites of typical fracture initiation in dental prosthetic constructs. Similar to enamel, adhesion of biomimetically textured LS2 could also show anisotropic behavior. Therefore, tensile bond strength (TBS) before and after thermocycling (TC) and interfacial characterization of biomimetically textured LS2 (parallel (PAR) or perpendicular (PER) crystal orientation) after different pre-treatment modes (hydrofluoric acid etching (HFE), grit blasting (GBL) and self-etching glass-ceramic primer (SGP)) were investigated. TC reduced significantly TBS for all specimens except for GBL. Biomimetic textured LS2 after HFE showed anisotropic behavior regarding adhesion. Crystal orientation reduced TBS for the PER HFE specimens after TC significantly. In general, the TBS of HFE specimens was still higher or not significantly lower compared to other pre-treatment modes like GBL or SGP. For the GBL and SGP specimens, crystal orientation had no influence on TBS and interfacial characteristics. In contrast HFE specimens showed different interfacial characteristics depending if they were PAR or PER texturized. Based on these findings, HFE of biomimetic textured LS2 can be recommended. For bonding, the PAR orientation is recommended as its adhesion potential is less prone to degrade.
CRIS-Team Scopus Importer:2019-05-09
Keywords: Anisotropic; Biomimetic material; Grit blasting; Hydrofluoric acid etching; Interfacial characterization; Lithium disilicate ceramics; Self-etching glass-ceramic primer; Tensile bond strength

Adipogenic, chondrogenic, osteogenic, and antimicrobial features of glass ceramic material supplemented with manganese - Rau, Julietta V.; De Stefanis, Adriana; Barbaro, Katia; Fosca, Marco; Yankova, Viktoriya G.; Matassa, Roberto; Nottola, Stefania Annarita; Nawaz, Qaisar; Ali, Muhammad Saad; Peukert, Wolfgang; Boccaccini, Aldo R. (Journal of Non-Crystalline Solids, 2021)
Innovative Mn-containing glass ceramic (Na2O[2.00]-K2O[0.09]-MgO[3.10]-MnO[2.07]-CaO[38.78]-CaF2[2.25]-P2O5[9.66]-SiO2[41.71] [wt%]) was obtained by sol-gel. It was investigated by High Resolution Field Emission Scanning Electron Microscopy, Energy Dispersive X-Ray Spectroscopy, X-Ray fluorescence, X-Ray Diffraction, and Fourier Transform Infrared Spectroscopy. Ion release characteristics of the glass ceramic powder were quantified via Inductively Coupled Plasma Optical Emission Spectroscopy. Biological tests were performed using equine adipose tissue mesenchymal stem cells (AMSCs). MTT assay demonstrated the cytocompatibility of the prepared material. AMSCs differentiation test showed that the glass ceramic favored the stem cell differentiation in adipogenic, chondrogenic, and osteogenic lineages, the last one being qualitatively more pronounced. The antimicrobial properties were evaluated against Escherichia coli, Enterococcus faecalis, Pseudomonas aeruginosa, Salmonella typhi, and Staphylococcus aureus bacteria strains and Candida albicans fungus. The inhibition of Gram-negative bacteria (S. tiphy, E. coli), Gram-positive (E. faecalis) and fungus (C. albicans) was detected, while the inhibition of P. aeruginosa and S. aureus was not significant.
CRIS-Team Scopus Importer:2021-02-19
Keywords: antimicrobial; bioactive glass; glass ceramic; manganese; osteogenic

Adipose- and bone marrow-derived mesenchymal stem cells display different osteogenic differentiation patterns in 3D bioactive glass-based scaffolds - Rath, Subha N.; Nooeaid, Patcharakamon; Arkudas, Andreas; Beier, Justus; Strobel, Leonie; Brandl, Andreas; Roether, Judith; Horch, Raymund E.; Boccaccini, Aldo R.; Kneser, Ulrich (Journal of Tissue Engineering and Regenerative Medicine, 2013)
Mesenchymal stem cells can be isolated from a variety of different sources, each having their own peculiar merits and drawbacks. Although a number of studies have been conducted comparing these stem cells for their osteo-differentiation ability, these are mostly done in culture plastics. We have selected stem cells from either adipose tissue (ADSCs) or bone marrow (BMSCs) and studied their differentiation ability in highly porous three-dimensional (3D) 45S5 Bioglass®-based scaffolds. Equal numbers of cells were seeded onto 5 × 5 × 4 mm(3) scaffolds and cultured in vitro, with or without osteo-induction medium. After 2 and 4 weeks, the cell-scaffold constructs were analysed for cell number, cell spreading, viability, alkaline phosphatase activity and osteogenic gene expression. The scaffolds with ADSCs displayed osteo-differentiation even without osteo-induction medium; however, with osteo-induction medium osteogenic differentiation was further increased. In contrast, the scaffolds with BMSCs showed no osteo-differentiation without osteo-induction medium; after application of osteo-induction medium, osteo-differentiation was confirmed, although lower than in scaffolds with ADSCs. In general, stem cells in 3D bioactive glass scaffolds differentiated better than cells in culture plastics with respect to their ALP content and osteogenic gene expression. In summary, 45S5 Bioglass-based scaffolds seeded with ADSCs are well-suited for possible bone tissue-engineering applications. Induction of osteogenic differentiation appears unnecessary prior to implantation in this specific setting. Copyright © 2013 John Wiley & Sons, Ltd.
UnivIS-Import:2015-03-09:Pub.2014.tech.IW.LM.adipos

Advanced ADA-GEL bioink for bioprinted artificial cancer models - Bednarzig, Vera; Karakaya, Emine; Leal-Egaña, Aldo; Teßmar, Jörg; Boccaccini, Aldo R.; Detsch, Rainer (Bioprinting, 2021)
One of the main problems encountered in cancer pathologies is the lack of proper in vitro systems resembling the architecture of tumoral tissues. Since 2D surfaces do not represent the morpho-mechanical characteristics of malignant milieus, 3D systems are rapidly gaining interest in the field of Biomaterials for Cancer Research. In this work, we used a new kind of hydrogel-based scaffold constituted by crosslinked alginate di-aldehyde (ADA) and gelatin (GEL) to mimic the tumoral milieu in vitro by biofabrication. For this purpose, flat 2D films and 3D bioprinted scaffolds were crosslinked with solutions of calcium, barium, and combinations of the two. These structures were analyzed in terms of their chemical and mechanical properties, as well as their biological compatibility in the presence of the tumoral cell line HCT116 (colorectal cancer). Our results indicate that ADA-GEL, crosslinked with these divalent ions, can perform effectively as an artificial cancer model, matching the mechanical properties of colorectal tumors, as well as enabling cell growth in confinement. Furthermore, the use of different combinations of divalent ions allowed the tailoring of the mechanical properties of the material. The cell-loaded ADA-GEL constructs are not significantly affected by the type of crosslinking ion. The best outcome was achieved when 3D printed structures were produced with an ADA concentration of 2.5 (w/v)% and crosslinked with barium, showing remarkable results in terms of printability and mechanical properties. With this composition and barium as the crosslinking ion, a stiffness of 44.97 kPa was achieved, compared with calcium crosslinked samples, where it was only possible to achieve an elastic modulus of 21.55 kPa. This work demonstrates that ADA-GEL-based matrices are a very interesting option to perform as tumor-like scaffolds, which could be used to improve current methods of drug testing as well as for personalized medicine.
CRIS-Team Scopus Importer:2021-06-11

Advanced alginate-based hydrogels - Detsch, Rainer; Sarker, Bapi; Zehnder, Tobias; Frank, Gerhard; Boccaccini, Aldo R. (Materials Today, 2015)

Advanced Biomaterials - Special Section: Euromat 2009-Materials for Healthcare - Boccaccini, Aldo R. (Advanced Engineering Materials, 2010)
UnivIS-Import:2015-03-09:Pub.2010.tech.IW.LM.advanc_6

Advancing bioinks for 3D bioprinting using reactive fillers: A review - Heid, Susanne; Boccaccini, Aldo R. (Acta Biomaterialia, 2020)
The growing demand for personalized implants and tissue scaffolds requires advanced biomaterials and processing strategies for the fabrication of three-dimensional (3D) structures mimicking the complexity of the extracellular matrix. During the last years, biofabrication approaches like 3D printing of cell-laden (soft) hydrogels have been gaining increasing attention to design such 3D functional environments which resemble natural tissues (and organs). However, often these polymeric hydrogels show poor stability and low printing fidelity and hence various approaches in terms of multi-material mixtures are being developed to enhance pre- and post-printing features as well as cytocompatibility and post-printing cellular development. Additionally, bioactive properties improve the binding to the surrounding (host) tissue at the implantation site. In this review we focus on the state-of-the-art of a particular type of heterogeneous bioinks, which are composed of polymeric hydrogels incorporating inorganic bioactive fillers. Such systems include isotropic and anisotropic silicates like bioactive glasses and nanoclays or calcium-phosphates like hydroxyapatite (HAp), which provide in-situ crosslinking effects and add extra functionality to the matrix, for example mineralization capability. The present review paper discusses in detail such bioactive composite bioink systems based on the available literature, revealing that a great variety has been developed with substantially improved bioprinting characteristics, in comparison to the pure hydrogel counterparts, and enabling high viability of printed cells. The analysis of the results of the published studies demonstrates that bioactive fillers are a promising addition to hydrogels to print stable 3D constructs for regeneration of tissues. Progress and challenges of the development and applications of such composite bioink approaches are discussed and avenues for future research in the field are presented. Statement of Significance: Biofabrication, involving the processing of biocompatible hydrogels including cells (bioinks), is being increasingly applied for developing complex tissue and organ mimicking structures. A variety of multi-material bioinks is being investigated to bioprint 3D constructs showing shape stability and long-term biological performance. Composite hydrogel bioinks incorporating inorganic bioreactive fillers for 3D bioprinting are the subject of this review paper. Results reported in the literature highlight the effect of bioactive fillers on bioink properties, printability and on cell behavior during and after printing and provide important information for optimizing the design of future bioinks for biofabrication, exploiting the extra functionalities provided by inorganic fillers. Further functionalization with drugs/growth factors can target enhanced printability and local drug release for more specialized biomedical therapies.
CRIS-Team Scopus Importer:2020-07-24
Keywords: Bioactive glasses; Bioactive inorganic fillers; Bioprinting; Cell encapsulation; Composite hydrogels; Hydroxyapatite; Laponite

Advancing Processing Technologies for Designed Geopolymers: 3D Printing and Mechanical Machining - Toniolo, Nicoletta; Bednarzig, Vera; Roether, Judith; Rost, Harald; Boccaccini, Aldo R. (Interceram, 2019)
Abstract: Geopolymers continue to attract interest owing to their good mechanical properties in combination with the ecofriendly fabrication process. However, the applications of geopolymers are still restricted to a limited field, mainly as construction materials. Designing and fabricating components of complex, intricate shape for applications beyond building materials may represent a useful approach to broaden geopolymer applications. In this study, unconventional processing and finishing technologies, such as direct ink printing, drilling, and machining are investigated to demonstrate their suitability for geopolymers. Fly ash-based geopolymers incorporating a relevant amount of waste glass demonstrated suitable flow properties to be used in a direct ink printing process. Moreover, the geopolymer specimens showed high machinability: components were drilled and machined in a lathe obtaining superior surface finish, uniform dimensional accuracy, and complex shape parts. The results presented herein indicate opportunities for expanding applications of geopolymers in areas such as mechanical engineering, where components with accurate, specifically designed shapes and surface finish are needed.
CRIS-Team Scopus Importer:2019-08-13

A facile and scalable method to produce superhydrophic stainless steel surface - Alonso Frank, Micael; Boccaccini, Aldo R.; Virtanen, Sannakaisa (Applied Surface Science, 2014)

Ag containing polydopamine coating on a melt-derived bioactive glass-ceramic: Effect on surface reactivity - Tejido-Rastrilla, R.; Baldi, G.; Boccaccini, Aldo R. (Ceramics International, 2018)
Keywords: Polydopamine; Silver; Antibacterial; Coatings; Bioactive glass-ceramic

Ag-doped 45S5 Bioglass-based bone scaffolds by molten salt ion exchange: processing and characterisation - Newby, P. J.; El-Gendy, R.; Kirkham, J.; Yang, X. B.; Thompson, I. D.; Boccaccini, Aldo R. (Journal of Materials Science: Materials in Medicine, 2011)
There is increasing interest in developing scaffolds with therapeutic and antibacterial potential for bone tissue engineering. Silver is a proven antibacterial agent which bacteria such as MRSA have little or no defense against. Using an ion exchange method, silver ions have been introduced into 45S5 Bioglass̄ based scaffolds that were fabricated using the foam replication technique. This technique allows the introduction of Ag+ ions onto the surface of the scaffold without compromising the scaffold bioactivity and other physical properties such as porosity. Controlling the amount of Ag+ ions introduced onto the surface of the scaffold was achieved by tailoring the ion exchange parameters to fabricate samples with repeatable and predictable Ag+ ion release behavior. In vitro studies in simulated body fluid were carried out to ensure that the scaffolds maintained their bioactivity after the introduction of Ag+ ions. It was also shown that the addition of low concentrations (2000:1 w/w) of silver ions supported the attachment and viability of human periodontal ligament stromal cells on the 3D scaffolds. This work has thus confirmed ion exchange as an effective technique to introduce Ag+ ions into 45S5 Bioglass̄ scaffolds without compromising the basic properties of 45S5 Bioglass̄ which are required for applications in bone tissue engineering. © Springer Science+Business Media, LLC 2011.
UnivIS-Import:2015-03-09:Pub.2011.tech.IW.LM.agdope_3

Ag-doped sol-gel derived novel composite materials for dental applications - Chatzistavrou, Xanthippi; Paraskevopoulos, Konstantinos M.; Salih, Vehid; Boccaccini, Aldo R.; Kasuga, Toshihiro (Key Engineering Materials, 2011)
UnivIS-Import:2015-03-09:Pub.2011.tech.IW.LM.agdope

Aging Time and Temperature Effects on the Structure and Bioactivity of Gel-Derived 45S5 Glass-Ceramics - Zheng, Kai; Solodovnyk, Anastasiia; Li, Wei; Goudouri, Ourania Menti; Staehli, Christoph; Nazhat, Showan N.; Boccaccini, Aldo R. (Journal of the American Ceramic Society, 2015)
Porous bioactive glass-ceramics based on the 45S5 Bioglass((R)) composition were fabricated by an acid-catalyzed sol-gel method. The effects of aging time and temperature on the structure and in vitro bioactivity were investigated. Fourier-transform infrared spectroscopy (FTIR) was carried out on the samples to understand the structure and to monitor the formation of hydroxyapatite (HA) after immersion in simulated body fluid (SBF). The bioactivity of gel-derived 45S5 glass-ceramic and amorphous 45S5 Bioglass((R)) was compared. The results showed that an increase in both aging time and temperature can enhance crystallization, whereas bioactivity is reduced with increasing aging time but not significantly influenced by aging temperature. Compared with amorphous 45S5 Bioglass((R)), gel-derived glass-ceramic aged for 3d at 60 degrees C exhibited a more rapid rate of HA formation after immersion for less than 7d. Amorphous 45S5 Bioglass((R)) showed higher HA formation rate after immersion in SBF for more than 7d, whereas the quantity of formed HA on gel-derived 45S5 glass-ceramic was still comparable to that of amorphous 45S5 Bioglass((R)) after immersion for 14d. It is suggested that the lower bioactivity of 45S5 glass-ceramics could be outweighed by the higher surface area and higher content of Si-NBO groups in gel-derived glass-ceramics. The results thus confirm that gel-derived 45S5 glass-ceramic exhibiting bioactivity comparable to that of amorphous 45S5 Bioglass((R)) can be fabricated by sol-gel method under suitable aging conditions.

Ag modified mesoporous bioactive glass nanoparticles for enhanced antibacterial activity in 3D infected skin model - Zheng, Kai; Balasubramanian, Preethi; Paterson, Thomas E.; Stein, René; MacNeil, Sheila; Fiorilli, Sonia; Vitale-Brovarone, Chiara; Shepherd, Joanna; Boccaccini, Aldo R. (Materials Science and Engineering C, 2019)
Bioactive glasses (BG)are versatile materials for various biomedical applications, including bone regeneration and wound healing, due to their bone bonding, antibacterial, osteogenic, and angiogenic properties. In this study, we aimed to enhance the antibacterial activity of SiO2-CaO mesoporous bioactive glass nanoparticles (MBGN)by incorporating silver (Ag)through a surface modification approach. The modified Ag-containing nanoparticles (Ag-MBGN)maintained spherical shape, mesoporous structure, high dispersity, and apatite-forming ability after the surface functionalization. The antibacterial activity of Ag-MBGN was assessed firstly using a planktonic bacteria model. Moreover, a 3D tissue-engineered infected skin model was used for the first time to evaluate the antibacterial activity of Ag-MBGN at the usage dose of 1 mg/mL. In the planktonic bacteria model, Ag-MBGN exhibited a significant antibacterial effect against both Pseudomonas aeruginosa and Staphylococcus aureus in comparison to non-engineered (Ag-free)MBGN and the blank control. Moreover, Ag-MBGN did not show cytotoxicity towards fibroblasts at the usage dose. However, in the 3D infected skin model, Ag-MBGN only demonstrated antibacterial activity against S. aureus whereas their antibacterial action against P. aeruginosa was inhibited. In conclusion, surface modification by Ag incorporation is a feasible approach to enhance the antibacterial activity of MBGN without significantly impacting their morphology, polydispersity, and apatite-forming ability. The prepared Ag-MBGN are attractive building blocks for the development of 3D antibacterial scaffolds for tissue engineering.
CRIS-Team Scopus Importer:2019-06-18
Keywords: 3D skin model; Antibacterial activity; Bioactive glasses; Nanoparticles; Silver

Air pollution control residues from waste incineration: current UK situation and assessment of alternative technologies - Rani, D. Amutha; Boccaccini, Aldo R.; Deegan, D.; Cheeseman, C. R. (Waste Management, 2008)
Current disposal options for APC residues in the UK and alternative treatment technologies developed world-wide have been reviewed. APC residues are currently landfilled in the UK where they undergo in situ solidification, although the future acceptability of this option is uncertain because the EU waste acceptance criteria (WAC) introduce strict limits on leaching that are difficult to achieve. Other APC residue treatment processes have been developed which are reported to reduce leaching to below relevant regulatory limits. The Ferrox process, the VKI process, the WES-PHix process, stabilisation/solidification using cementitious binders and a range of thermal treatment processes are reviewed. Thermal treatment technologies convert APC residues combined with other wastes into inert glass or glass-ceramics that encapsulate heavy metals. The waste management industry will inevitably use the cheapest available option for treating APC residues and strict interpretation and enforcement of waste legislation is required if new, potentially more sustainable technologies are to become commercially viable. © 2007 Elsevier Ltd. All rights reserved.
UnivIS-Import:2015-03-09:Pub.2008.tech.IW.LM.airpol

Alginate and gelatine blending for bone cell printing and biofabrication - Detsch, Rainer; Sarker, Bapi; Grigore, Alexandra; Boccaccini, Aldo R. (10th IASTED International Conference on Biomedical Engineering, BioMed 2013, 2013)
In order to develop suitable materials for biofabrication, the current work focused on the fabrication and characterization of alginate-gelatine matrices. Alginate-gelatine blends were prepared by mixing the stock solutions of alginate and gelatine in different ratios: 80/20 and 60/40. Films of these materials were chemical and mechanical characterised. To evaluate the cell behaviour of the different soft matrices, MG-63 osteoblast-like cells were employed. As a consequence, all investigated alginate matrices are suitable for cell encapsulation or rapid prototyping, promoting high cell viability. However, the most promising material is alginate blended with gelatin due to the extensive cell-matrix interactions and cell ability to migrate and proliferate through the hydrogel.
Keywords: Alginate - Gelatine blending; Cell printing; Soft matrices

Alginate-based hydrogels show the same complex mechanical behavior as brain tissue - Distler, Thomas; Schaller, Emely; Steinmann, Paul; Boccaccini, Aldo R.; Budday, Silvia (Journal of the Mechanical Behavior of Biomedical Materials, 2020)
Mimicking the mechanical properties of native human tissues is one key route in tissue engineering. However, the successful cre- ation of functional tissue equivalents requires the comprehensive understanding of the complex and nonlinear mechanical properties of both native tissues and biomaterials. Here, we demonstrate that it is possible to replicate the complex mechanical behavior of soft tissues, exemplary shown for porcine brain tissue, under multiple loading conditions, compression, tension, and torsional shear, through simple blends of alginate and gelatin hydrogels. Alginate exhibits a pronounced compression-tension asymmetry and a nonlinear behavior, while gelatin shows an almost linear response. Blended together, alginate-gelatin (ALG-GEL) hydrogels can resemble the characteristic nonlinear, conditioning, and compression-tension-asymmetric behavior of brain tissue. We demonstrate that hydrogel concentration and incubation effectively tune the stiffness and loading-mode-specific stress relaxation behavior. The stiffness increases with increasing hydrogel concentration and decreases with increasing incubation time. In addition, we observe slower stress relaxation after long incubation times. Our systematic approach highlights the importance of single component, multi-modal mechanical analysis of hydrogels to understand the distinct structure-mechanics relation of each hydrogel component to eventually mimic the response of native tissues. The presented dataset will allow for the structurally derived compositional design of hydrogels for a broad variety of tissue engineering applications.
Keywords: biomechanics; nonlinear material behavior; tissue engineering; brain tissue; alginate-gelatin hydrogels

Alginate-based hydrogels with improved adhesive properties for cell encapsulation - Sarker, Bapi; Rompf, Julia; Silva, Raquel; Lang, Nadine; Detsch, Rainer; Kaschta, Joachim; Fabry, Ben; Boccaccini, Aldo R. (International Journal of Biological Macromolecules, 2015)
Hydrogel-based biomaterials are ideal scaffolding matrices for microencapsulation, but they need to be modified to resemble the mechanical, structural and chemical properties of the native extracellular matrix. Here, we compare the mechanical properties and the degradation behavior of unmodified and modified alginate hydrogels in which cell adhesive functionality is conferred either by blending or covalently cross-linking with gelatin. Furthermore, we measure the spreading and proliferation of encapsulated osteoblast-like MG-63 cells. Alginate hydrogels covalently crosslinked with gelatin show the highest degree of cell adhesion, spreading, migration, and proliferation, as well as a faster degradation rate, and are therefore a particularly suitable material for microencapsulation.
Keywords: Alginate; Cell encapsulation; Hydrogel

Alginate/Bioglass® composite coatings on stainless steel deposited by direct current and alternating current electrophoretic deposition - Chen, Qiang; Cordero Arias, Luis Eduardo; Roether, Judith; Cabanas Polo, Sandra; Virtanen, Sannakaisa; Boccaccini, Aldo R. (Surface & Coatings Technology, 2013)
Direct current (DC) and alternating current (AC) electrophoretic deposition (EPD) approaches involving different number of EPD cycles were developed for the fabrication of alginate/Bioglass® composite coatings from water-based suspensions. The high stability of the colloidal suspension was confirmed by zeta-potential assessment and the properties of coatings deposited from both DC-EPD and AC-EPD were quantitatively compared by using a range of characterization methods. The deposition yield and coating composition were determined by mass and thermogravimetric analysis. Coatings with different microstructure and thickness were observed by scanning electron microscopy. Significant differences in surface roughness and hydrophilicity (determined by water contact angle measurement) of coatings obtained by DC-EPD and AC-EPD were identified and discussed. The coating adhesion strength and corrosion resistance were evaluated by standard tape test and electrochemical method, respectively, and the experimental data showed the superior adhesion and corrosion resistance of AC-EPD coatings compared to DC-EPD coatings. In order to investigate the in vitro bioactivity, all coatings were immersed in simulated body fluid for 7. days. Results from Fourier transform infrared spectroscopy (FTIR) analysis showed the typical characteristic peaks of hydroxyapatite formed on both DC- and AC-EPD coatings. Based on the results of this study, bioactive alginate/Bioglass® coatings are proposed as suitable candidates for applications in dental and orthopedic metallic implants and for bone tissue scaffolds. © 2013 Elsevier B.V.
UnivIS-Import:2015-03-09:Pub.2013.tech.IW.LM.algina
Keywords: Alginate; Bioactive glass; Bioactivity; Biomedical coatings; Electrophoretic deposition

Alginate Core–Shell Capsules for 3D Cultivation of Adipose-Derived Mesenchymal Stem Cells - Nebel, Sabrina; Lux, Manuel; Kuth, Sonja; Bider, Faina; Dietrich, Wolf; Egger, Dominik; Boccaccini, Aldo R.; Kasper, Cornelia (Bioengineering, 2022)
Mesenchymal stem cells (MSCs) are primary candidates in tissue engineering and stem cell therapies due to their intriguing regenerative and immunomodulatory potential. Their ability to self-assemble into three-dimensional (3D) aggregates further improves some of their therapeutic properties, e.g., differentiation potential, secretion of cytokines, and homing capacity after administration. However, high hydrodynamic shear forces and the resulting mechanical stresses within commercially available dynamic cultivation systems can decrease their regenerative properties. Cells embedded within a polymer matrix, however, lack cell-to-cell interactions found in their physiological environment. Here, we present a “semi scaffold-free” approach to protect the cells from high shear forces by a physical barrier, but still allow formation of a 3D structure with in vivo-like cell-to-cell contacts. We highlight a relatively simple method to create core–shell capsules by inverse gelation. The capsules consist of an outer barrier made from sodium alginate, which allows for nutrient and waste diffusion and an inner compartment for direct cell-cell interactions. Next to capsule characterization, a harvesting procedure was established and viability and proliferation of human adipose-derived MSCs were investigated. In the future, this encapsulation and cultivation tech-nique might be used for MSC-expansion in scalable dynamic bioreactor systems, facilitating down-stream procedures, such as cell harvest and differentiation into mature tissue grafts.
CRIS-Team Scopus Importer:2022-03-04
Keywords: 3D cell cultivation technologies; Alginate; Cell expansion; Core–shell capsule; Mesenchymal stem cells

Alginate utilization in tissue engineering and cell therapy - Sarker, Bapi; Boccaccini, Aldo R. (Springer Science and Business Media, LLC, 2018)
Due to the structural similarity to the extracellular matrix, nowadays, hydrogels are widely used for tissue engineering applications. Among the various hydrogels, alginate is considered a very useful biomaterial that has found numerous applications in the biomedical field due to its favorable properties, including biocompatibility and ease of gelation. It has been used to design tissue engineering constructs of various structures, such as porous scaffolds, microspheres, films, and microcapsules for drug and cell delivery and various tissue engineering applications particularly for bone, cartilage, muscle, and vascular tissue engineering. This chapter will provide a comprehensive overview of the applications of alginate-based hydrogels as various forms of constructs and scaffolds for tissue engineering.
CRIS-Team Scopus Importer:2022-08-05
Keywords: Alginate; Bioprinting; Hydrogel; Scaffold; Tissue engineering

A lifetime prediction method based on cumulative flaw length theory - Boccaccini, D. N.; Maioli, M.; Cannio, M.; Dlouhy, Ivo; Romagnoli, Marcello; Leonelli, Cristina; Boccaccini, Aldo R. (Journal of the European Ceramic Society, 2012)
Ultrasonic pulse velocity testing (UPVT) was carried out to perform non-destructive quality control of refractory plates. Used in conjunction with fracture mechanics, ultrasonic velocity measurements have proved a powerful technique for detecting, positioning and sizing internal voids and cracks in the samples, originated from the manufacturing process. Two cordierite-mullite refractory compositions exhibiting different microstructure and crack propagation behaviour were characterized through their lifetime during which they were subjected to thermal shock loading. In this paper, a new statistical method is proposed which allows to estimate the lifetime when the stress state that will be applied in service (loading) and the scattering of the ultrasonic velocity data in the as-received state are known. Since this lifetime prediction method is based on a non-destructive technique, it could be implemented into a code in an automatic quality control device for continuous lifetime estimation. The correlation between crack propagation behaviour and thermal shock resistance is discussed and semi-empirical models were developed to predict the service life of refractory plates from the measured values of ultrasonic velocities on as-received samples. © 2011 Elsevier Ltd.
UnivIS-Import:2015-03-09:Pub.2012.tech.IW.LM.alifet
Keywords: Cumulative Flaw Length Theory; Mullite; Non-destructive evaluation; Residual stress; Thermal shock resistance

Aligned Ice Templated Biomaterial Strategies for the Musculoskeletal System - Diaz, Florencia; Forsyth, Nicholas; Boccaccini, Aldo R. (Advanced Healthcare Materials, 2023)
Aligned pore structures present many advantages when conceiving biomaterial strategies for treatment of musculoskeletal disorders. Aligned ice templating (AIT) is one of the many different techniques capable of producing anisotropic porous scaffolds; its high versatility allows for the formation of structures with tunable pore sizes, as well as the use of many different materials. AIT has been found to yield improved compressive properties for bone tissue engineering (BTE), as well as higher tensile strength and optimized cellular alignment and proliferation in tendon and muscle repair applications. This review evaluates the work that has been done in the last decade toward the production of aligned pore structures by AIT with an outlook on the musculoskeletal system. This work describes the fundamentals of the AIT technique and focuses on the research carried out to optimize the biomechanical properties of scaffolds by modifying the pore structure, categorizing by material type and application. Related topics including growth factor incorporation into AIT scaffolds, drug delivery applications, and studies about immune system response will be discussed.
CRIS-Team Scopus Importer:2023-05-12
Keywords: aligned scaffolds; biomaterials; bone tissue engineering; musculoskeletal system; unidirectional freezing

Aligned PCL/Collagen electrospun nanofibers for skeletal muscle tissue engineering using benign solvents - Dippold, Dirk; Schubert, Dirk W.; Beier, Justus; Boccaccini, Aldo R. (14th Bayreuth Polymer Symposium, 2015)

Alkali-free processing of advanced open-celled sinter-crystallized glass-ceramics - Elsayed, Hamada; Monich, Patricia Rabelo; Savio, Gianpaolo; Hartmann, Malte; Boccaccini, Aldo R.; Galusek, Dusan; Kraxner, Jozef; Bernardo, Enrico (International Journal of Applied Glass Science, 2021)
The cooling of a melt corresponding to the eutectic between wollastonite (CaSiO3) and diopside (CaMgSi2O6) determines the synthesis of an interesting example of alkali-free bioactive glass, easily converted into glass-ceramics featuring two silicate phases, coupled also with akermanite (Ca2MgSi2O7), by sinter-crystallization of fine glass powders at 1000 degrees C. The fabrication of scaffolds by digital light processing of glass powders suspended in a photo-curable, sacrificial binder, is a well-established technique; the present paper aims at disclosing novel approaches, concerning the topology of scaffolds, offering components with remarkable strength, especially in bending conditions. As an alternative, glass-ceramic foams were fabricated by the firing of porous precursors derived from the gelation of suspensions of glass powders in alkali-free basic aqueous solution.
CRIS-Team WoS Importer:2021-05-28

Alternating current electrophoretic deposition (EPD) of TiO2 nanoparticles in aqueous suspensions - Chavez-Valdez, Alejandra; Herrmann, Martin; Boccaccini, Aldo R. (Journal of Colloid and Interface Science, 2012)
UnivIS-Import:2015-03-09:Pub.2012.tech.IW.LM.altern

Alternating current electrophoretic deposition of antibacterial bioactive Glass-Chitosan composite coatings - Seuß, Sigrid; Lehmann, Maja; Boccaccini, Aldo R. (International Journal of Molecular Sciences, 2014)
Alternating current (AC) electrophoretic deposition (EPD) was used to produce multifunctional composite coatings combining bioactive glass (BG) particles and chitosan. BG particles of two different sizes were used, i.e., 2 μm and 20-80 nm in average diameter. The parameter optimization and characterization of the coatings was conducted by visual inspection and by adhesion strength tests. The optimized coatings were investigated in terms of their hydroxyapatite (HA) forming ability in simulated body fluid (SBF) for up to 21 days. Fourier transform infrared (FTIR) spectroscopy results showed the successful HA formation on the coatings after 21 days. The first investigations were conducted on planar stainless steel sheets. In addition, scaffolds made from a TiAl4V6 alloy were considered to show the feasibility of coating of three dimensional structures by EPD. Because both BG and chitosan are antibacterial materials, the antibacterial properties of the as-produced coatings were investigated using E. coli bacteria cells. It was shown that the BG particle size has a strong influence on the antibacterial properties of the coatings. © 2014 by the authors; licensee MDPI, Basel, Switzerland.
Keywords: Antibacterial; Bioactive glass; Chitosan; Coatings; Electrophoretic deposition

Alternating electric field stimulation: Phenotype analysis and osteoclast activity of differentiated RAW 264.7 macrophages on hydroxyapatite-coated Ti6Al4V surfaces and their crosstalk with MC3T3-E1 pre-osteoblasts - Kreller, Thomas; Zimmermann, J.; van Rienen, U.; Boccaccini, Aldo R.; Jonitz-Heincke, A.; Detsch, Rainer (Biomaterials Advances, 2023)
Biophysical stimuli can mimic endogenous electric potentials and currents in the natural bone to enhance tissue healing and reconstruction in diseased bone. However, little is known about the influence of electric fields on osteoclasts. Therefore, this study aimed to investigate the effects of alternating electric fields on osteoclast differentiation and activity. In this in vitro study, RAW 264.7 cells were seeded on Ti6Al4V substrates, as a loadbearing implant material modified with biomimetic calcium phosphate (BCP) and stimulated towards osteoclastic differentiation via growth factors. The effects of directly coupled alternating electric fields (0.7 Vrms, 20 Hz) on cell behavior were examined for up to 28 days. Alternating electric field simulation was performed using the finite element method. Changes in cell and substrate morphology were examined via light and fluorescence imaging. Cell viability was assessed via WST-8 assay. The effect of electrical stimulation (ES) on intercellular signaling and crosstalk was evaluated using indirect co-cultures with murine MC3T3-E1 pre-osteoblasts by qPCR. Morphological analysis proved the successful differentiation of macrophages into osteoclast-like cells for both electrically stimulated samples as well as unstimulated controls. ES promoted RAW 264.7 viability within the first seven days and induced a cellular response at gene expression levels. Gradually decreased expression rates of genes related to osteoclast differentiation and activity within 28 days could indicate a long-term inhibitory effect of ES on osteoclastogenesis and osteoclast activity while significantly upregulated carbonic anhydrase type 2 expressions could be a consequence of membrane depolarization to maintain intercellular pH levels. In this context, we were also able to demonstrate the degradation of the BCP surface by cellular influence. ES affected the crosstalk between osteoblast-, and osteoclast-like cells. Supernatants of electrically stimulated RAW 264.7 specimens led to decreased MC3T3-E1 viabilities and mineralization. While osteopontin expression in MC3T3-E1 cells was significantly decreased, markers of osteogenic differentiation showed higher expression rates. Underlying biophysical mechanisms in combination with biomaterials are part of ongoing research.
CRIS-Team Scopus Importer:2023-01-20
Keywords: Alternating electric fields; Electrical stimulation; Hydroxyapatite; Osteoclasts; RAW 264.7

Ambient Temperature Drying Shrinkage and Cracking in Metakaolin-Based Geopolymers - Kuenzel, Carsten; Vandeperre, Luc J.; Donatello, Shane; Boccaccini, Aldo R.; Cheeseman, Chris (Journal of the American Ceramic Society, 2012)
Ambient temperature drying shrinkage in metakaolin-based geopolymer pastes exposed to low relative humidity environments has been investigated. The effect of varying the geopolymer composition (water content, Si:Al ratio, Na:Al ratio, and Na + or K + cations) on the sensitivity to ambient temperature drying shrinkage is reported. The definition of " structural" water as being the minimum water content required that prevents contractions in the gel structure, and thus drying shrinkage from occurring, is introduced. From the results presented, it is clear that the ionic charge density of cations, the total quantity of cations, and the relative quantities and stabilities of cation: AlO 4 - pairs in the paste are major factors affecting the sensitivity of pastes to ambient temperature drying shrinkage. © 2012 The American Ceramic Society.
UnivIS-Import:2015-03-09:Pub.2012.tech.IW.LM.ambien

A model of the mechanical degradation of foam replicated scaffolds - Sulong, M. A.; Belova, I. V.; Boccaccini, Aldo R.; Murch, G. E.; Fiedler, T. (Journal of Materials Science, 2016)
Tissue engineering scaffolds are implants that actively support tissue growth whilst providing mechanical support. For optimum functionality, they are designed to slowly dissolve in vivo so that no foreign material remains permanently implanted inside the body. The current study uses a simple degradation model that estimates the change of scaffold geometry due to surface erosion. This model is applied on scaffolds that have been manufactured using the foam replication method. In order to capture their complex geometry, micro-computed tomography scans of samples are obtained. Their change in geometry and degradation of mechanical properties is evaluated using computational analysis. The present investigation found that the mechanical properties such as the quasi-elastic gradient, 0.2 % offset yield stress and the plateau stress are decreased systematically over a 10-week period of immersion time. Deformation analysis on the titania foam scaffold is performed by means of the deformed model obtained from finite element calculations.

Amorphous Calcium Phosphate and Amorphous Calcium Phosphate Carboxylate: Synthesis and Characterization - Indurkar, Abhishek; Choudhary, Rajan; Rubenis, Kristaps; Nimbalkar, Mansingraj; Sarakovskis, Anatolijs; Boccaccini, Aldo R.; Locs, Janis (ACS Omega, 2023)
Amorphous calcium phosphate (ACP) is the first solid phase precipitated from a supersaturated calcium phosphate solution. Naturally, ACP is formed during the initial stages of biomineralization and stabilized by an organic compound. Carboxylic groups containing organic compounds are known to regulate the nucleation and crystallization of hydroxyapatite. Therefore, from a biomimetic point of view, the synthesis of carboxylate ions containing ACP (ACPC) is valuable. Usually, ACP is synthesized with fewer steps than ACPC. The precipitation reaction of ACP is rapid and influenced by pH, temperature, precursor concentration, stirring conditions, and reaction time. Due to phosphates triprotic nature, controlling pH in a multistep approach becomes tedious. Here, we developed a new ACP and ACPC synthesis approach and thoroughly characterized the obtained materials. Results from vibration spectroscopy, nuclear magnetic resonance (NMR), X-ray photoelectron spectroscopy (XPS), true density, specific surface area, and ion release studies have shown a difference in the physiochemical properties of the ACP and ACPC. Additionally, the effect of a carboxylic ion type on the physiochemical properties of ACPC was characterized. All of the ACPs and ACPCs were synthesized in sterile conditions, and in vitro analysis was performed using MC-3T3E1 cells, revealing the cytocompatibility of the synthesized ACPs and ACPCs, of which the ACPC synthesized with citrate showed the highest cell viability.
CRIS-Team Scopus Importer:2023-08-25

Amorphous, Carbonated Calcium Phosphate and Biopolymer-Composite-Coated Si3N4/MWCNTs as Potential Novel Implant Materials - Furko, Monika; Detsch, Rainer; Horváth, Zsolt E.; Balázsi, Katalin; Boccaccini, Aldo R.; Balázsi, Csaba (Nanomaterials, 2024)
A biodegradable amorphous carbonated calcium phosphate (caCP)-incorporated polycaprolactone (PCL) composite layer was successfully deposited by a spin coater. In this specific coating, the PCL acts as a bioadhesive, since it provides a better adherence of the coatings to the substrate compared to powder coatings. The caCP–PCL coatings were deposited and formed thin layers on the surface of a Si3N4–3 wt% MWCNT (multiwalled carbon nanotube) substrate, which is an emerging type of implant material in the biomedical field. The composite coatings were examined regarding their morphology, structure and biological performance. The biocompatibility of the samples was tested in vitro with MC3T3-E1 preosteoblast cells. Owing to the caCP–PCL thin layer, the cell viability values were considerably increased compared to the substrate material. The ALP and LDH tests showed numerous living cells on the investrigated coatings. The morphology of the MC3T3-E1 cells was examined by fluorescent staining (calcein and DAPI) and scanning electron microscopy, both of which revealed a well-spread, adhered and confluent monolayer of cells. All performed biocompatibility tests were positive and indicated the applicability of the deposited thin composite layers as possible candidates for orthopaedic implants for an extended period.
CRIS-Team Scopus Importer:2024-02-16
Keywords: amorphous calcium phosphate; biocomposites; biopolymers; MWCNT; Si

A Multifunctional Scaffold for Bone Infection Treatment by Delivery of microRNA Therapeutics Combined With Antimicrobial Nanoparticles - Sadowska, Joanna M.; Power, Rachael N.; Genoud, Katelyn J.; Matheson, Austyn; González-Vázquez, Arlyng; Costard, Lara; Eichholz, Kian; Pitacco, Pierluca; Hallegouet, Tanguy; Chen, Gang; Curtin, Caroline M.; Murphy, Ciara M.; et al. (Advanced Materials, 2023)
Treating bone infections and ensuring bone repair is one of the greatest global challenges of modern orthopedics, made complex by antimicrobial resistance (AMR) risks due to long-term antibiotic treatment and debilitating large bone defects following infected tissue removal. An ideal multi-faceted solution would will eradicate bacterial infection without long-term antibiotic use, simultaneously stimulating osteogenesis and angiogenesis. Here, a multifunctional collagen-based scaffold that addresses these needs by leveraging the potential of antibiotic-free antimicrobial nanoparticles (copper-doped bioactive glass, CuBG) to combat infection without contributing to AMR in conjunction with microRNA-based gene therapy (utilizing an inhibitor of microRNA-138) to stimulate both osteogenesis and angiogenesis, is developed. CuBG scaffolds reduce the attachment of gram-positive bacteria by over 80%, showcasing antimicrobial functionality. The antagomiR-138 nanoparticles induce osteogenesis of human mesenchymal stem cells in vitro and heal a large load-bearing defect in a rat femur when delivered on the scaffold. Combining both promising technologies results in a multifunctional antagomiR-138-activated CuBG scaffold inducing hMSC-mediated osteogenesis and stimulating vasculogenesis in an in vivo chick chorioallantoic membrane model. Overall, this multifunctional scaffold catalyzes killing mechanisms in bacteria while inducing bone repair through osteogenic and angiogenic coupling, making this platform a promising multi-functional strategy for treating and repairing complex bone infections.
CRIS-Team Scopus Importer:2023-12-15
Keywords: biomaterials; bone infection; gene therapy; microRNA

An elastomeric patch derived from poly(glycerol sebacate) for delivery of embryonic stem cells to the heart - Chen, Qi-Zhi; Ishii, Hikaru; Thouas, George A.; Lyon, Alexander R.; Wright, Jamie S.; Blaker, Jonny J.; Chrzanowski, Wojciech; Boccaccini, Aldo R.; Ali, Nadire N.; Knowles, Jonathan C.; Harding, Sian E. (Biomaterials, 2010)
We hypothesize that a combinatorial approach of ventricle constraint and stem cell therapy would offer a greater benefit for the treatment of heart failure than either strategy alone. A heart patch would serve two therapeutic purposes: biomechanical support and cell delivery. In this study, we describe a hybrid heart patch engineered from a synthetic elastomer, poly(glycerol sebacate) (PGS), supplemented with cardiomyocytes differentiated from human embryonic stem cells (hESCs). In line with two therapeutically relevant considerations, i.e. biocompatibility and cell delivery efficiency, the PGS was (a) pre-conditioned in culture medium for 6 days, and (b) prepared without gelatin coatings to facilitate detachment and delivery of cardiomyocytes following patch implantation. Following pre-conditioning under physiological conditions, the PGS patch material without gelatin coating was found to satisfactorily support cardiomyocyte viability and attachment, with active cell beating for periods of longer than 3 months until interrupted. Dynamic culture studies revealed that cells detached more efficiently from the uncoated surface of PGS than from gelatin-coated PGS. No significant differences were detected between the beating rates of human embryonic stem cell-derived cardiomyocytes on tissue culture plate and the pre-conditioned and gelatin-uncoated PGS. PGS patches sutured over the left ventricle of rats in vivo remained intact over a 2 week period without any deleterious effects on ventricular function. We conclude that PGS is a suitable biomaterial for stem cell-based regeneration strategies to restore cardiomyocyte function, and the hybrid heart patch engineered under optimal conditions would be a promising support device for the cardiac repair. © 2010 Elsevier Ltd.
UnivIS-Import:2015-03-09:Pub.2010.tech.IW.LM.anelas
Keywords: Embryonic stem cell; Heart; In vitro; In vivo; Poly(glycerol sebacate)

A New Calcium Releasing Nano-composite Biomaterial for Bone Tissue Engineering Scaffolds - Cattalini, J. P.; Garcia, J.; Boccaccini, Aldo R.; Lucangioli, S.; Mourino, (Procedia Engineering, 2013)
A biomaterial with bioactive glass nanoparticles (nBG) and Ca2+ incorporated into alginate matrix was developed. Films characterization was carried out by SEM, IR, tensile strength measurements, bioactivity assay, degradation and swelling studies. Ca2+ release from films was analyzed. Freeze-dried-scaffolds were also fabricated. Films showed the development of a homogeneous matrix and the mechanical properties were improved when nBG were incorporated. The bioactive nature of nBG containing films was confirmed by studies in simulated body fluid. Degradation was negligible and a good swelling capacity was observed. Moreover Ca2+ was released in a controlled manner. In scaffolds fabricated by freeze-drying, pores were seen to be uniform and well distributed. According to the characterization results, these composite biomaterials are attractive candidates for the fabrication of bone tissue engineering scaffolds. © 2013 The Authors.
UnivIS-Import:2015-03-09:Pub.2013.tech.IW.LM.anewca
Keywords: Biomaterials; Calcium; Composites; Films; Scaffolds

A new generation of electrospun fibers containing bioactive glass particles for wound healing - Sergi, Rachele; Cannillo, Valeria; Boccaccini, Aldo R.; Liverani, Liliana (Materials, 2020)
Chitosan fibers blended with polyethylene oxide (CHIT_PEO) and crosslinked with genipin were fabricated by electrospinning technique. Subsequently, CHIT_PEO bioactive glass composite electrospun mats were fabricated with the aim to achieve flexible structures with adequate mechanical properties and improved biological performance respect to CHIT_PEO fibers, for potential applications in wound healing. Three different compositions of bioactive glasses (BG) were selected and investigated: 45S5 BG, a Sr and Mg containing bioactive glass (BGMS10) and a Zn-containing bioactive glass (BGMS_2Zn). Particulate BGs (particles size < 20 µm) were separately added to the starting CHIT_PEO solution before electrospinning. The two recently developed bioactive glasses (BGMS10 and BGMS_2Zn) showed very promising biological properties in terms of bioactivity and cellular viability; thus, such compositions were added for the first time to CHIT_PEO solution to fabricate composite electrospun mats. The incorporation of bioactive glass particles and their distribution into CHIT_PEO fibers were assessed by SEM and FTIR analyses. Furthermore, CHIT_PEO composite electrospun mats showed improved mechanical properties in terms of Young’s Modulus compared to neat CHIT_PEO fibers; on the contrary, the values of tensile strain at break (%) were comparable. Biological performance in terms of cellular viability was investigated by means of WST-8 assay and CHIT_PEO composite electrospun mats showed cytocompatibility and the desired cellular viability.
CRIS-Team Scopus Importer:2020-12-25
Keywords: Bioactive glasses; Chitosan; Composite fibers; Electrospinning; Mechanical properties; Wound healing

A new strategy for developing chitosan conversion coating on magnesium substrates for orthopedic implants - Francis, A.; Yang, Yuyun; Boccaccini, Aldo R. (Applied Surface Science, 2019)
Keywords: Magnesium; Simulated body fluid; Chemical conversion coating; Bioactive glass; Corrosion; Chitosan

Angiogenic effects of ionic dissolution products released from a boron-doped 45S5 bioactive glass - Haro Durand, Luis A.; Vargas, Gabriela E.; Romero, Nelida M.; Vera-Mesones, Rosa; Porto-Lopez, Jose M.; Boccaccini, Aldo R.; Zago, Maria P.; Baldi, Alberto; Gorustovich, Alejandro (Journal of Materials Chemistry B, 2015)
In regenerative medicine of vascularized tissues, there is a great interest in the use of biomaterials that are able to stimulate angiogenesis, a process necessary for rapid revascularization to allow the transport and exchange of oxygen, nutrients, growth factors and cells that take part in tissue repair and/or regeneration. An increasing number of publications have shown that bioactive glasses stimulate angiogenesis. Because it has been established that boron (B) may play a role in angiogenesis, the aim of this study was to assess the in vivo angiogenic effects of the ionic dissolution products that from a bioactive glass (BG) in the 45S5 system doped with 2 wt% B2O3 (45S5.2B). The pro-angiogenic capacity of 45S5.2B BG was assessed on the vasculature of the embryonic quail chorioallantoic membrane (CAM). Ionic dissolution products from 45S5.2B BG increased angiogenesis. This is quantitatively evidenced by the greater expression of integrin alpha(v)beta(3) and higher vascular density in the embryonic quail CAM. The response observed at 2 and 5 days post-treatment was equivalent to that achieved by applying 10 mu g mL(-1) of basic fibroblast growth factor. These results show that the ionic dissolution products released from the bioactive glass 45S5.2B stimulate angiogenesis in vivo. The effects observed are attributed to the presence the ionic dissolution products, which contained 160 +/- 10 mu M borate.

Angiogenic potential of bioactive glasses - Gorustovich, Alejandro A.; Durand, Luis A.Haro; Roether, Judith; Boccaccini, Aldo R. (Imperial College Press, 2013)
CRIS-Team Scopus Importer:2022-08-05

Angiogenic potential of boron-containing bioactive glasses: in vitro study - Balasubramanian, Preethi; Hupa, Leena; Jokic, Bojan; Detsch, Rainer; Grünewald, Alina; Boccaccini, Aldo R. (Journal of Materials Science, 2017)

An Innovative Arteriovenous (AV) Loop Breast Cancer Model Tailored for Cancer Research - An, Ran; Strissel, Pamela; Al-Abboodi, Majida; Robering, Jan Willem; Reakasame, Supachai; Eckstein, Markus; Peddi, Ajay; Hauck, Theresa; Bäuerle, Tobias; Boccaccini, Aldo R.; Youssef, Almoatazbellah; Sun, Jiaming; et al. (Bioengineering, 2022)
Animal models are important tools to investigate the pathogenesis and develop treatment strategies for breast cancer in humans. In this study, we developed a new three-dimensional in vivo arteriovenous loop model of human breast cancer with the aid of biodegradable materials, including fibrin, alginate, and polycaprolactone. We examined the in vivo effects of various matrices on the growth of breast cancer cells by imaging and immunohistochemistry evaluation. Our findings clearly demonstrate that vascularized breast cancer microtissues could be engineered and recapitulate the in vivo situation and tumor-stromal interaction within an isolated environment in an in vivo organism. Alginate–fibrin hybrid matrices were considered as a highly powerful material for breast tumor engineering based on its stability and biocompatibility. We propose that the novel tumor model may not only serve as an invaluable platform for analyzing and understanding the molecular mechanisms and pattern of oncologic diseases, but also be tailored for individual therapy via transplantation of breast cancer patient-derived tumors.
CRIS-Team Scopus Importer:2022-07-15
Keywords: animal model; arteriovenous loop; breast cancer

An in vitro evaluation of the biological and osteogenic properties of magnesium-doped bioactive glasses for application in bone tissue engineering - Hohenbild, Frederike; Arango Ospina, Marcela; Schmitz, Sarah I.; Moghaddam, Arash; Boccaccini, Aldo R.; Westhauser, Fabian (International Journal of Molecular Sciences, 2021)
Magnesium (Mg2+ ) is known to play a crucial role in mineral and matrix metabolism of bone tissue and is thus increasingly considered in the field of bone tissue engineering. Bioactive glasses (BGs) offer the promising possibility of the incorporation and local delivery of therapeutically active ions as Mg2+ . In this study, two Mg2+-doped derivatives of the ICIE16-BG composition (49.46 SiO2, 36.27 CaO, 6.6 Na2 O, 1.07 P2 O5, 6.6 K2 O (mol%)), namely 6Mg-BG (49.46 SiO2, 30.27 CaO, 6.6 Na2 O, 1.07 P2 O5, 6.6 K2 O, 6.0 MgO (mol%) and 3Mg-BG (49.46 SiO2, 33.27 CaO, 6.6 Na2 O, 1.07 P2 O5, 6.6 K2 O, 3.0 MgO (mol%)) were examined. Their influence on viability, proliferation and osteogenic differentiation of human mesenchymal stromal cells (MSCs) was explored in comparison to the original ICIE16-BG. All BGs showed good biocompatibility. The Mg2+-doped BGs had a positive influence on MSC viability alongside with inhibiting effects on MSC proliferation. A strong induction of osteogenic differentiation markers was observed, with the Mg2+-doped BGs significantly outperforming the ICIE16-BG regarding the expression of genes encoding for protein members of the osseous extracellular matrix (ECM) at certain observation time points. However, an overall Mg2+-induced enhancement of the expression of genes encoding for ECM proteins could not be observed, possibly due to a too moderate Mg2+ release. By adaption of the Mg2+ release from BGs, an even stronger impact on the expression of genes encoding for ECM proteins might be achieved. Furthermore, other BG-types such as mesoporous BGs might provide a higher local presence of the therapeutically active ions and should therefore be considered for upcoming studies.
CRIS-Team Scopus Importer:2021-12-03
Keywords: Human mesenchymal stromal cell; ICIE16 bioactive glass; Magnesium; Osteogenic differentiation; Therapeutically active ions

Anisotropic composites of desaminotyrosine and desaminotyrosyl tyrosine functionalized gelatin and bioactive glass microparticles - Julich-Gruner, Konstanze K.; Lendlein, Andreas; Boccaccini, Aldo R.; Neffe, Axel T. (Materials Research Society Symposium - Proceedings, 2015)
Functionalization of gelatin with desaminotyrosine (DAT) and desamino tyrosyl tyrosine (D ATT) has been demonstrated to allow network formation based on non-covalent interactions of the aromatic moieties. Based on the observation that the DAT(T) groups furthermore could interact with hydroxyapatite fillers, here it was investigated whether such interactions of DAT(T) could also be employed to stabilize composites formed by functionalized gelatins and bioactive glass (BG) particles. Because of sedimentation of the BG microparticles during the gelification, anisotropic composites with two distinct layers were formed. The characterization of mechanical properties by tensile tests and rheology showed that all composites of non-functionalized and DAT(T) functionalized gelatins with BG microparticles showed an increased Young's modulus (E) up to 3 MPa, an increased storage modulus (G′) up to 100 kPa, increased tensile strength (σ) up to 3.4 MPa, and increased loss modulus (G″) compared to the pure matrices. As the observed effects were more pronounced in the DAT(T) functionalized gelatins compared to non-functionalized gelatins, and a much increased thermal stability of these composites was found, it is likely that there are binding interactions between the aromatic moieties and the BG microparticles. This effect open opportunities for the further development of this type of gelatin-based composites for bone regeneration applications.

Anode-Selective Electrophoretic Deposition of a Bioactive Glass/Sulfone-Containing Click Polyester Composite - Nagao, Yu; Takasu, Akinori; Boccaccini, Aldo R. (Macromolecules, 2012)
A room temperature thiol-ene click polymerization afforded a poly(ester-sulfide) (M n = 1.4-6.9 ×10 4), which represents the first in a new class of click polyesters. Subsequent oxone oxidation of the poly(ester-sulfide) led to the corresponding poly(ester-sulfone), which had improved thermal stability in comparison with the parent poly(ester-sulfide). A bioactive glass/poly(ester-sulfone) composite could be deposited on a stainless-steel anode by electrophoretic deposition (EPD). Hydroxyapatite was found on the surface of electrophoretically deposited bioactive glass/poly(ester-sulfone) composites that had been immersed in simulated body fluid (SBF) for 2 weeks. This bioactive glass/poly(ester-sulfone) composite might therefore find use as a surface coating for implantable medical devices on which a hydroxyapatite layer can form post implantation to strengthen the interface between the implant and host bone. © 2012 American Chemical Society.
UnivIS-Import:2015-03-09:Pub.2012.tech.IW.LM.anodes

An organic-inorganic hybrid scaffold with honeycomb-like structures enabled by one-step self-assembly-driven electrospinning - Ding, Yaping; Li, Wei; Schubert, Dirk W.; Boccaccini, Aldo R.; Roether, Judith; Santos, Hélder A. (Materials Science and Engineering C, 2021)
Electrospun organic/inorganic hybrid scaffolds have been appealing in tissue regeneration owing to the integrated physicochemical and biological performances. However, the conventional electrospun scaffolds with non-woven structures usually failed to enable deep cell infiltration due to the densely stacked layers among the fibers. Herein, through self-assembly-driven electrospinning, a polyhydroxybutyrate/poly(ε-caprolactone)/58S sol-gel bioactive glass (PHB/PCL/58S) hybrid scaffold with honeycomb-like structures was prepared by manipulating the solution composition and concentration during a one-step electrospinning process. The mechanisms enabling the formation of self-assembled honeycomb-like structures were investigated through comparative studies using Fourier-transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) between PHB/PCL/58S and PHB/PCL/sol-gel silica systems. The obtained honeycomb-like structure was built up from nanofibers with an average diameter of 370 nm and showed a bimodal distribution of pores: large polygonal pores up to hundreds of micrometers within the honeycomb-cells and irregular pores among the nanofibers ranging around few micrometers. The cell-materials interactions were further studied by culturing MG-63 osteoblast-like cells for 7 days. Cell viability, cell morphology and cell infiltration were comparatively investigated as well. While cells merely proliferated on the surface of non-woven structures, MG-63 cells showed extensive proliferation and deep infiltration up to 100–200 μm into the honeycomb-like structure. Moreover, the cellular spatial organization was readily regulated by the honeycomb-like pattern as well. Overall, the newly obtained hybrid scaffold may integrate the enhanced osteogenicity originating from the bioactive components, and the improved cell-material interactions brought by the honeycomb-like structure, making the new scaffold a promising candidate for tissue regeneration.
CRIS-Team Scopus Importer:2021-05-21
Keywords: Electrospinning; Honeycomb-like architecture; Organic-inorganic hybrid scaffolds; Self-assembly

A novel local drug delivery system: Superhydrophobic titanium oxide nanotube arrays serve as the drug reservoir and ultrasonication functions as the drug release trigger - Zhou, Juncen; Alonso Frank, Micael; Yang, Yuyun; Boccaccini, Aldo R.; Virtanen, Sannakaisa (Materials Science and Engineering C, 2018)

Antibacterial 45S5 Bioglass®-based scaffolds reinforced with genipin cross-linked gelatin for bone tissue engineering - Li, Wei; Wang, Hui; Ding, Yaping; Scheithauer, Ellen Corinna; Goudouri, Ourania Menti; Grünewald, Alina; Detsch, Rainer; Agarwal, Seema; Boccaccini, Aldo R. (Journal of Materials Chemistry B, 2015)
45S5 Bioglass® (BG) scaffolds with high porosity (>90%) were coated with genipin cross-linked gelatin (GCG) and further incorporated with poly(p-xylyleneguanidine) hydrochloride (PPXG). The obtained GCG coated scaffolds maintained the high porosity and well interconnected pore structure. A 26-fold higher compressive strength was provided to 45S5 BG scaffolds by GCG coating, which slightly retarded but did not inhibit the in vitro bioactivity of 45S5 BG scaffolds in SBF. Moreover, the scaffolds were made antibacterial against both Gram-positive and Gram-negative bacteria by using polyguanidine, i.e. PPXG, in this study. Osteoblast-like cells (MG-63) were seeded onto PPXG and GCG coated scaffolds. PPXG was biocompatible with MG-63 cells at a low concentration (10 μg mL-1). MG-63 cells were shown to attach and spread on both uncoated and GCG coated scaffolds, and the mitochondrial activity measurement indicated that GCG coating had no negative influence on the cell proliferation behavior of MG-63 cells. The developed novel antibacterial bioactive 45S5 BG-based composite scaffolds with improved mechanical properties are promising candidates for bone tissue engineerin

Antibacterial activity and biocompatibility of zein scaffolds containing silver-doped bioactive glass - El-Rashidy, Aiah A.; Waly, Gihan; Gad, Ahmed; Roether, Judith; Hum, Jasmin; Yang, Yuyun; Detsch, Rainer; Hashem, Azza A.; Sami, Inas; Goldmann, Wolfgang; Boccaccini, Aldo R. (Biomedical Materials, 2018)
Keywords: zein scaffolds; silver; in vitro biocompatibility; bioactive glass; antibacterial

Antibacterial and antioxidant activity of cinnamon essential oil-laden 45S5 bioactive glass/soy protein composite scaffolds for the treatment of bone infections and oxidative stress - Ünalan, Irem; Fuggerer, Tim; Slavik, Benedikt; Büttner, Andrea; Boccaccini, Aldo R. (Materials Science and Engineering C, 2021)
This study aimed to fabricate cinnamon essential oil (CO)-laden 45S5 bioactive glass (BG)/soy protein (SP) scaffolds exhibiting antioxidant and antibacterial activity. In this regard, 45S5 BG-based scaffolds were produced by the foam replica method, and subsequently the scaffolds were coated with various concentrations of CO (2.5, 5 and 7 (v/v) %) incorporated SP solution. Scanning electron microscopy images revealed that the CO-laden SP effectively attached to the 45S5 BG scaffold struts. The presence of 45S5 BG, SP and CO was confirmed using Fourier transform infrared spectroscopy. Compressive strength results indicated that SP based coatings improved the scaffolds' mechanical properties compared to uncoated BG scaffolds. The loading efficiency and releasing behaviour of the different CO concentrations were tested by gas chromatography-mass spectroscopy and UV–Vis spectroscopy. The results showed that CO incorporated scaffolds have controlled releasing behaviour over seven days. Furthermore, the coating on the scaffold surfaces slightly retarded, but it did not inhibit, the in vitro bioactivity of the scaffolds. Moreover, the antioxidant and antibacterial activity of CO was studied. The free radical scavenging activity measured by DPPH was 5 ± 1, 41 ± 3, 44 ± 1 and 43 ± 1 % for BGSP, CO2.5, CO5 and CO7, respectively. The antioxidant activity was thus enhanced by incorporating CO. Agar diffusion and colony counting results indicated that the incorporation of CO increased the antibacterial activity of scaffolds against S. aureus and E. coli. In addition, cytotoxicity of the scaffolds was investigated using MG-63 osteoblast-like cells. The results showed that the BG-SP scaffold was non-toxic under the investigated conditions, whereas dose-dependent toxicity was observed in CO-laden scaffolds. Considered together, the developed phytotherapeutic agent laden 45S5 BG-based scaffolds are promising for bone tissue engineering exhibiting capability to combat bone infections and to protect against oxidative stress damage.
CRIS-Team Scopus Importer:2021-08-06
Keywords: 45S5 bioactive glass; And bone infection; Antibacterial activity; Antioxidant activity; Cinnamon essential oil

Antibacterial and Bioactive Coatings Based on Radio Frequency Co-Sputtering of Silver Nanocluster-Silica Coatings on PEEK/Bioactive Glass Layers Obtained by Electrophoretic Deposition - Ur Rehman, Muhammad Atiq; Ferraris, Sara; Goldmann, Wolfgang H; Perero, Sergio; Bastan, Fatih Erdem; Nawaz, Qaisar; Confiengo, G. Gautier di; Ferraris, Monica; Boccaccini, Aldo R. (ACS Applied Materials and Interfaces, 2017)
<span style="color: rgb(0, 0, 0); font-family: Helvetica, Arial, sans-serif; font-size: 14px; font-style: normal; font-variant-ligatures: normal; font-variant-caps: normal; font-weight: 500; letter-spacing: normal; orphans: 2; text-align: left; text-indent: 0px; text-transform: none; white-space: normal; widows: 2; word-spacing: 0px; -webkit-text-stroke-width: 0px; background-color: rgb(244, 249, 253); text-decoration-style: initial; text-decoration-color: initial; display: inline !important; float: none;">Bioactive and antibacterial coatings on stainless steel substrates were developed and characterized in this study. Silver nanocluster–silica composite coatings of 60–150 nm thickness were deposited using radio frequency (RF) co-sputtering on PEEK/bioactive glass (BG) layers (of 80–90 μm thickness) which had been electrophoretically deposited onto stainless steel. Two sputtering conditions were used by varying the deposition time (15 and 40 min); the resulting microstructure, composition, adhesion strength, in vitro bioactivity, and antibacterial activity were investigated. Scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), and energy dispersive spectroscopy (EDX) confirmed the presence of silver nanoclusters, which were homogeneously embedded in the silica matrix. The isoelectric point of the coatings and their charge at physiological pH were determined by zeta potential measurements. The presence of BG particles in the PEEK/BG layer allows the coatings to form apatite-like crystals upon immersion in simulated body fluid (SBF). Moreover, silver nanoclusters embedded in the silica matrix as a top layer provided an antibacterial effect against <i style="font-style: italic; color: rgb(0, 0, 0); font-family: Helvetica, Arial, sans-serif; font-size: 14px; font-variant-ligatures: normal; font-variant-caps: normal; font-weight: 500; letter-spacing: normal; orphans: 2; text-align: left; text-indent: 0px; text-transform: none; white-space: normal; widows: 2; word-spacing: 0px; -webkit-text-stroke-width: 0px; background-color: rgb(244, 249, 253); text-decoration-style: initial; text-decoration-color: initial;">Escherichia coli<span style="color: rgb(0, 0, 0); font-family: Helvetica, Arial, sans-serif; font-size: 14px; font-style: normal; font-variant-ligatures: normal; font-variant-caps: normal; font-weight: 500; letter-spacing: normal; orphans: 2; text-align: left; text-indent: 0px; text-transform: none; white-space: normal; widows: 2; word-spacing: 0px; -webkit-text-stroke-width: 0px; background-color: rgb(244, 249, 253); text-decoration-style: initial; text-decoration-color: initial; display: inline !important; float: none;"> and <i style="font-style: italic; color: rgb(0, 0, 0); font-family: Helvetica, Arial, sans-serif; font-size: 14px; font-variant-ligatures: normal; font-variant-caps: normal; font-weight: 500; letter-spacing: normal; orphans: 2; text-align: left; text-indent: 0px; text-transform: none; white-space: normal; widows: 2; word-spacing: 0px; -webkit-text-stroke-width: 0px; background-color: rgb(244, 249, 253); text-decoration-style: initial; text-decoration-color: initial;">Staphylococcus carnosus<span style="color: rgb(0, 0, 0); font-family: Helvetica, Arial, sans-serif; font-size: 14px; font-style: normal; font-variant-ligatures: normal; font-variant-caps: normal; font-weight: 500; letter-spacing: normal; orphans: 2; text-align: left; text-indent: 0px; text-transform: none; white-space: normal; widows: 2; word-spacing: 0px; -webkit-text-stroke-width: 0px; background-color: rgb(244, 249, 253); text-decoration-style: initial; text-decoration-color: initial; display: inline !important; float: none;">.
Keywords: antibacterial coatings; bioactive coatings; bioactive glass; electrophoretic deposition; PEEK; RF sputtering; silver

Antibacterial biohybrid nanofibers for wound dressings - Homaeigohar, Shahin; Boccaccini, Aldo R. (Acta Biomaterialia, 2020)
Globally, chronic wounds impose a notable burden to patients and healthcare systems. Such skin wounds are readily subjected to bacteria that provoke inflammation and hence challenge the healing process. Furthermore, bacteria induce infection impeding re-epithelialization and collagen synthesis. With an estimated global market of 20.4 billion by 2021, appropriate wound dressing materials e.g. those composed of biopolymers originating from nature, are capable of alleviating the infection incidence and of accelerating the healing process. Particularly, biopolymeric nanofibrous dressings are biocompatible and mostly biodegradable and biomimic the extracellular matrix structure. Such nanofibrous dressings provide a high surface area and the ability to deliver antibiotics and antibacterial agents locally into the wound milieu to control infection. In this regard, with the dangerous evolution of antibiotic resistant bacteria, antibiotic delivery systems are being gradually replaced with antibacterial biohybrid nanofibrous wound dressings. This emerging class of wound dressings comprises biopolymeric nanofibers containing antibacterial nanoparticles, nature-derived compounds and biofunctional agents. Here, the most recent (since 2015) developments of antibacterial biopolymeric nanofibrous wound dressings, particularly those made of biohybrids, are reviewed and their antibacterial efficiency is evaluated based on a comprehensive literature analysis. Lastly, the prospects and challenges are discussed to draw a roadmap for further progresses and to open up future research avenues in this area. Statement of Significance: With a global market of 20.4 billion by 2021, skin wound dressings are a crucial segment of the wound care industry. As an advanced class of bioactive wound dressing materials, natural polymeric nanofibers loaded with antibacterial agents, e.g. antimicrobial nanoparticles/ions, nature-derived compounds and biofunctional agents, have shown a remarkable potential for replacement of their classic counterparts. Also, given the expanding concern regarding antibiotic resistant bacteria, such biohybrid nanofibrous wound dressings can outperform classical drug delivery systems. Here, an updated overview of the most recent (since 2015) developments of antibacterial biopolymeric nanofibrous wound dressings is presented. In this review, while discussing about the antibacterial efficiency of such systems, the prospects and challenges are highlighted to draw a roadmap for further progresses in this area.
CRIS-Team Scopus Importer:2020-03-20
Keywords: Antibacterial agent; Biohybrid; Electrospinning; Nanofiber; Wound dressing

Antibacterial Composite Materials Based on the Combination of Polyhydroxyalkanoates With Selenium and Strontium Co-substituted Hydroxyapatite for Bone Regeneration - Marcello, Elena; Maqbool, Muhammad; Nigmatullin, Rinat; Cresswell, Mark; Jackson, Philip R.; Basnett, Pooja; Knowles, Jonathan C.; Boccaccini, Aldo R.; Roy, Ipsita (Frontiers in Bioengineering and Biotechnology, 2021)
Due to the threat posed by the rapid growth in the resistance of microbial species to antibiotics, there is an urgent need to develop novel materials for biomedical applications capable of providing antibacterial properties without the use of such drugs. Bone healing represents one of the applications with the highest risk of postoperative infections, with potential serious complications in case of bacterial contaminations. Therefore, tissue engineering approaches aiming at the regeneration of bone tissue should be based on the use of materials possessing antibacterial properties alongside with biological and functional characteristics. In this study, we investigated the combination of polyhydroxyalkanoates (PHAs) with a novel antimicrobial hydroxyapatite (HA) containing selenium and strontium. Strontium was chosen for its well-known osteoinductive properties, while selenium is an emerging element investigated for its multi-functional activity as an antimicrobial and anticancer agent. Successful incorporation of such ions in the HA structure was obtained. Antibacterial activity against Staphylococcus aureus 6538P and Escherichia coli 8739 was confirmed for co-substituted HA in the powder form. Polymer-matrix composites based on two types of PHAs, P(3HB) and P(3HO-co-3HD-co-3HDD), were prepared by the incorporation of the developed antibacterial HA. An in-depth characterization of the composite materials was conducted to evaluate the effect of the filler on the physicochemical, thermal, and mechanical properties of the films. In vitro antibacterial testing showed that the composite samples induce a high reduction of the number of S. aureus 6538P and E. coli 8739 bacterial cells cultured on the surface of the materials. The films are also capable of releasing active ions which inhibited the growth of both Gram-positive and Gram-negative bacteria.
CRIS-Team Scopus Importer:2021-05-07
Keywords: antibacterial; composites; hydroxyapatite; polyhydroxyalkanoates; selenium; strontium

Antibacterial, pro-angiogenic and pro-osteointegrative zein-bioactive glass/copper based coatings for implantable stainless steel aimed at bone healing - Ramos Rivera, Laura; Cochis, Andrea; Biser, Sarah; Canciani, Elena; Ferraris, Sara; Rimondini, Lia; Boccaccini, Aldo R. (Bioactive Materials, 2021)
Stainless steel implants are suitable candidates for bone replacement due to their cytocompatibility and mechanical resistance, but they suffer from lack of bioactivity and are prone to bacterial infections. Accordingly, to overcome those limitations, in this study we developed by electrophoretic deposition (EPD), an innovative surface coating made of (i) zein, a natural fibroblast-friendly polymer, (ii) bioactive glass, a pro-osteogenic inorganic material and (iii) copper containing bioactive glass, an antibacterial and pro-angiogenic material. FESEM images confirmed that porous, uniform and free of cracks coatings were obtained by EPD; moreover, coatings were resistant to mechanical stress as demonstrated by the tape test, resulting in a 4B classification of adhesion to the substrate. The coatings were cytocompatible as indicated by metabolism evaluation of human fibroblasts, endothelial cells and mature or progenitor osteoblasts cultivated in direct contact with the specimens. They also maintained pro-osteogenic properties towards undifferentiated progenitor cells that expressed osteogenic genes after 15 days of direct cultivation. Copper conferred antibacterial properties as biofilm formation of the joint pathogens Staphylococcus aureus, Staphylococcus epidermidis and Escherichia coli was significantly reduced in comparison with copper-free coatings (p < 0.05). Moreover, this anti-infective activity resulted as targeted towards bacteria while the cells viability was preserved when cells and bacteria were cultivated in the same environment by a co-culture assay. Finally, copper ability to recruit blood vessels and to inhibit bacterial infection was confirmed in vivo where the growth of S. aureus biofilm was inhibited and the formation of new (<50 μm diameter spread) blood vessels was observed.
CRIS-Team Scopus Importer:2020-11-27
Keywords: Antibacterial; Bioactive glass; Bone; Copper; Zein

Antibacterial properties of metal and metalloid ions in chronic periodontitis and peri-implantitis therapy - Goudouri, Ourania Menti; Kontonasaki, Eleana; Lohbauer, Ulrich; Boccaccini, Aldo R. (Acta Biomaterialia, 2014)
Periodontal diseases like periodontitis and peri-implantitis have been linked with Gram-negative anaerobes. The incorporation of various chemotherapeutic agents, including metal ions, into several materials and devices has been extensively studied against periodontal bacteria, and materials doped with metal ions have been proposed for the treatment of periodontal and peri-implant diseases. The aim of this review is to discuss the effectiveness of materials doped with metal and metalloid ions already used in the treatment of periodontal diseases, as well as the potential use of alternative materials that are currently available for other applications but have been proved to be cytotoxic to the specific periodontal pathogens. The sources of this review included English articles using Google Scholar™, ScienceDirect, Scopus and PubMed. Search terms included the combinations of the descriptors "disease", "ionic species" and "bacterium". Articles that discuss the biocidal properties of materials doped with metal and metalloid ions against the specific periodontal bacteria were included. The articles were independently extracted by two authors using predefined data fields. The evaluation of resources was based on the quality of the content and the relevance to the topic, which was evaluated by the ionic species and the bacteria used in the study, while the final application was not considered as relevant. The present review summarizes the extensive previous and current research efforts concerning the use of metal ions in periodontal diseases therapy, while it points out the challenges and opportunities lying ahead. © 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
Keywords: Antibacterial properties; Metal and metalloid ions; Peri-implantitis; Periodontitis

Anti-biofilm properties of bioactive glasses embedding organic active compounds - Galarraga-Vinueza, M. E.; Mesquita-Guimaraes, Joana; Magini, R. S.; Souza, J. C. M.; Fredel, M. C.; Boccaccini, Aldo R. (Journal of Biomedical Materials Research Part A, 2017)
Keywords: anti-biofilm activity; antibacterial compounds; bioactive glass; drug delivery system; mesoporous materials

Anti-inflammatory and antibacterial activities of cerium-containing mesoporous bioactive glass nanoparticles for drug-free biomedical applications - Kurtuldu, Fatih; Kankova, Hana; Beltrán, Ana M.; Liverani, Liliana; Galusek, Dusan; Boccaccini, Aldo R. (Materials Today Bio, 2021)
Mesoporous bioactive glass nanoparticles (MBGNPs) are attracting significant attention as suitable materials for multifunctional biomedical applications. In this study, cerium was incorporated into MBGNPs using two different approaches. In the first approach, cerium was added to the glass system directly during the synthesis, while in the second approach, cerium was added to the as-synthesized MBGNPs via the template ion-exchange method. The influence of the method of synthesis on the physicochemical properties of nanoparticles was examined by SEM, TEM, XRD, FTIR, and N2 adsorption-desorption analyses. The MBGNPs exhibited spheroidal morphology and disordered mesoporous structure. XRD analysis confirmed the amorphous nature of the nanoparticles. The chemical composition was determined by the acid digestion method using ICP-OES. The influence of the synthesis method on the specific surface area, mesoporosity, and solubility of synthesized nanoparticles in Tris/HCl (pH 7.4) and acetate (pH 4.5) buffer has also been studied. The obtained Ce containing MBGNPs were non-cytotoxic toward ​preosteoblast MC3T3-E1 cells in contact with nanoparticles in a concentration of up to 100 ​μg/mL. The anti-inflammatory effect of Ce containing MBGNPs was tested with lipopolysaccharides (LPS)-induced proinflammatory RAW 264.7 macrophage cells. Ce containing MBGNPs decreased the release of nitric oxide, indicating the anti-inflammatory response of macrophage cells. Ce containing MBGNPs also showed antibacterial activity against S. aureus and E. coli. The mentioned features of the obtained MBGNPs make them useful in a variety of biomedical applications, considering their biocompatibility, anti-inflammatory response, and enhanced antibacterial effect.
Keywords: Metal ion; Bioactive glassses; Nanoparticles; Anti-inflammation activity; Antibacterial materials

Antioxidant mesoporous Ce-doped bioactive glass nanoparticles with anti-inflammatory and pro-osteogenic activities - Zheng, Kai; Torre, Elisa; Bari, Alessandra; Taccardi, Nicola; Cassinelli, Clara; Morra, Marco; Fiorilli, Sonia; Vitale-Brovarone, Chiara; Iviglia, Giorgio; Boccaccini, Aldo R. (Materials Today Bio, 2020)
Mesoporous bioactive glass nanoparticles (MBGNs) are emerging biomaterials for bone repair/regeneration, considering their favorable pro-osteogenic and proangiogenic activities. To further improve their therapeutic effects, the endowment of MBGNs with additional antioxidant properties is of particular interest to target oxidative stress related to bone remodeling and diseases. To this end, we developed antioxidant cerium-containing MBGNs (Ce-MBGNs) (particle size of 100–300 ​nm) by using a postimpregnation strategy to incorporate Ce, through which the shape, pore structure, and dispersity of the nanoparticles were preserved. The incorporated amount of Ce could be tailored by adjusting the concentration of the Ce precursor solution. When impregnated at a relatively low temperature (20 ​°C), Ce-MBGNs containing either 1.8 or 2.8 ​mol% of Ce were produced, while the formation of by-product cerium oxide nanoparticles (nanoceria) could be avoided. In both developed Ce-MBGNs, the concentration of Ce4+ was higher than that of Ce3+, while the relative molar percentage of Ce4+ was similar (∼74%) in both Ce-MBGNs. The obtained Ce-MBGNs were evidenced to be non-cytotoxic against fibroblasts at the concentration of 1 ​mg/mL. Moreover, the incorporation of Ce into MBGNs significantly reduced the expression of oxidative stress–related genes in macrophages (J774a.1). Particularly in the presence of pro-oxidation agents, Ce-MBGNs could downregulate the expression of oxidative stress–related genes in comparsion with the polystyrene plates (control). When cultured with Ce-MBGNs, the expression of proinflammatory-related genes in macrophages could also be downregulated in comparsion with MBGNs and the control. Ce-MBGNs also exhibited pro-osteogenic activities through suppressing pro-osteoclastogenic responses. The obtained results highlight the great potential of the developed Ce-MBGNs in a variety of biomedical applications, particularly in treating bone defects under inflammatory conditions, considering their antioxidant, anti-inflammatory, and pro-osteogenesis activities.
CRIS-Team Scopus Importer:2020-02-25
Keywords: Anti-inflammatory; Antioxidant; Bioactive particles; Cerium; Pro-osteogenesis; Surface modification

Apatite forming ability and dissolution behavior of boron- And calcium-modified silicon oxycarbides in comparison to silicate bioactive glass - Xie, Fangtong; Gonzalo Juan, Isabel; Arango Ospina, Marcela; Riedel, Ralf; Boccaccini, Aldo R.; Ionescu, Emanuel (ACS Biomaterials Science and Engineering, 2019)
The bioactivity of Ca and/or B modified silicon oxycarbides has been assessed in vitro upon immersion in SBF (simulated body fluid). In the context of the present work, bioactivity refers to the likeliness of hydroxyapatite crystallization (biomineralization) on the surface of a material when in contact with physiological fluids. The incorporation of Ca and B into the silicon oxycarbide glass network is found to increase its bioactivity, which seems to scale with the content of Ca; thus, SiOC glass with a relatively large Ca/Si molar ratio (i.e., 0.12) is shown to exhibit bioactive characteristics similar to those of the benchmark silicate bioactive glass of 45S5 composition. The release kinetics of the SiOC glasses modified with Ca and/or B during the SBF test was studied by inductively coupled plasma-optical emission spectroscopy. It has been observed that the Si release kinetics can be correlated with the Ca content in the SiOC glasses: SiOC based glasses modified with Ca exhibited low Si release activation energies (i.e., 0.07 eV), being comparable to that of 45S5 bioactive glass (i.e., 0.04 eV); whereas silicon oxycarbides without Ca modification showed higher activation energies for Si release (i.e., 0.27 eV).
CRIS-Team Scopus Importer:2019-10-18
Keywords: bioactive glass; bioactivity; network connectivity; silicon oxycarbide

Apatite Mineralization Process from Silicocarnotite Bioceramics: Mechanism of Crystal Growth and Maturation - Andrea Rincon-Lopez, July; Andrea Hermann-Munoz, Jennifer; Cinca-Luis, Nuria; Lopez-Conesa, Lluis; Andres Fernandez-Benavides, David; Garcia-Cano, Irene; Maria Guilemany-Casadamon, Jose; Boccaccini, Aldo R.; Munoz-Saldana, Juan; Manuel Alvarado-Orozco, Juan (Crystal Growth and Design, 2020)
A mechanism for the formation and crystallization processes of bone-like apatite grown on non-stoichiometric silicocarnotite (SC) is here proposed. Single-phase SC powders and ceramics were obtained from fixed mixtures of hydroxyapatite and bioactive glass 45S5. The bioactive behavior of SC was assessed by immersion in Hank's solution at different times. Afterward, a systematic theoretical-experimental study of the structural properties at the micro- and nanoscale using transmission electron microscopy was performed and correlated with scanning electron microscopy, energy-dispersive X-ray spectroscopy, X-ray diffraction, and Raman techniques to determine the apatite mineralization process from the SC phase. The initial stage of apatite formation from SC was identified as the hydration and further polymerization of silanol groups, resulting in a silica-based hydrogel, which plays a critical role in the ionic exchange. As a result of the adsorption of ionic species from the medium into the silica-based hydrogel, the precipitation of crystalline apatitic structures starts through the emergence of newly formed SC nanocrystals, which act as a template for the crystallization process of a substituted apatite with SC-like structure. Then, because of the polymorphism between SC and HAp structures, the apatite layer retains the SC periodic arrangement following an epitaxial-like growth mechanism. Identification of the apatite layer formation mechanism is critical to understand its physical and chemical properties, which controls the long-term dissolution/precipitation rate of bioactive materials and their performance in the biological environment.
CRIS-Team WoS Importer:2020-06-26

Application of a neural network approach to the electrophoretic deposition of PEEK-alumina composite coatings - Corni, Ilaria; Cannio, Maria; Romagnoli, Marcello; Boccaccini, Aldo R. (Materials Research Bulletin, 2009)
Nano-size Al2O3-polyetheretherketone(PEEK) composite thick films have been prepared on stainless steel substrates from non-aqueous colloidal suspensions by electrophoretic deposition (EPD). The effects on the deposition efficiency of process parameters, such as the deposition time, the difference of potential applied and their interactions were studied using a neural network approach to develop a quantitative understanding of the system. Furthermore the use of the neural network was optimized in the number of epochs, hidden layers and artificial neurons in each hidden layer by a design of experiment (DOE) analysis, demonstrating that these two methods can work together improving the final results of the neural network approach. Afterwards, a MonteCarlo analysis based on a simulation of 100,000 virtual depositions has permitted to deeply investigate the effect of independent variables (e.g. deposition time and difference of potential applied) on the deposition yield (dependent variable). © 2009 Elsevier Ltd. All rights reserved.
UnivIS-Import:2015-03-09:Pub.2009.tech.IW.LM.applic
Keywords: A. Ceramics; A. Composites; A. Thin films

Application of Calcium Alginate Hydrogels in Semisolid Extrusion 3D Printed for the Production of Easy-to-Swallow Tablets - Falcone, Giovanni; Kuth, Sonja; Boccaccini, Aldo R.; Aquino, Rita P.; Esposito, Tiziana; Russo, Paola (Advanced Engineering Materials, 2023)
To maximize the potential of 3D printing, several technological issues must be overcome, especially in the case of semisolid extrusion (SSE), where the 3D model is built up through the well-defined extrusion of polymeric ink. Focusing on natural polymers, their physicochemical properties should be deeply investigated to evaluate 3D printability. This study aims to produce tablets easy to swallow, exploiting as 3D printing ink a crosslinked alginate hydrogel added of sorbitol, speculating that the plasticising action of sorbitol should allow to improve tablets' swallowability. Three different amounts of 70% sorbitol solution (5%, 15%, 25% v/v) are evaluated to identify the best composition in terms of both printing and technological properties. The data obtained from the chemical, rheological, and mechanical evaluation of each ink are related to the printing performance, to reach the best manufacturing reproducibility. Linear regression fitting study (r(2) = 0.9982) confirms the predictable relationship between residual mass of final platforms and sorbitol amount loaded. To characterize the final products, all dried batches are subjected to technological evaluation highlighting differences in the matrix softability as well as in the swelling/erosion properties after the interaction with biological fluids.
CRIS-Team WoS Importer:2023-02-03

Applications of Graphene Electrophoretic Deposition. A Review - Chavez-Valdez, Alejandra; Shaffer, M. S. P.; Boccaccini, Aldo R. (Journal of Physical Chemistry B, 2013)
This Review summarizes research progress employing electrophoretic deposition (EPD) to fabricate graphene and graphene-based nanostructures for a wide range of applications, including energy storage materials, field emission devices, supports for fuel cells, dye-sensitized solar cells, supercapacitors and sensors, among others. These carbonaceous nanomaterials can be dispersed in organic solvents, or more commonly in water, using a variety of techniques compatible with EPD. Most deposits are produced under constant voltage conditions with deposition time also playing an important role in determining the morphology of the resulting graphene structures. In addition to simple planar substrates, it has been shown that uniform graphene-based layers can be deposited on three-dimensional, porous, and even flexible substrates. In general, electrophoretically deposited graphene layers show excellent properties, e.g., high electrical conductivity, large surface area, good thermal stability, high optical transparency, and robust mechanical strength. EPD also enables the fabrication of functional composite materials, e.g., graphene combined with metallic nanoparticles, with other carbonaceous materials (e.g., carbon nanotubes) or polymers, leading to novel nanomaterials with enhanced optical and electrical properties. In summary, the analysis of the available literature reveals that EPD is a simple and convenient processing method for graphene and graphene-based materials, which is easy to apply and versatile. EPD has, therefore, a promising future for applications in the field of advanced nanomaterials, which depend on the reliable manipulation of graphene and graphene-containing systems. © 2012 American Chemical Society.
UnivIS-Import:2015-03-09:Pub.2013.tech.IW.LM.applic

Architecture-promoted biomechanical performance-tuning of tissue-engineered constructs for biological intervertebral disc replacement - Lang, Gernot; Obri, Katja; Saravi, Babak; Boccaccini, Aldo R.; Früh, Anton; Seidenstücker, Michael; Kurz, Bodo; Schmal, Hagen; Rolauffs, Bernd (Materials, 2021)
Background: Biological approaches to intervertebral disc (IVD) restoration and/or regeneration have become of increasing interest. However, the IVD comprises a viscoelastic system whose biological replacement remains challenging. The present study sought to design load-sharing twocomponent model systems of circular, nested, concentric elements reflecting the nucleus pulposus and annulus fibrosus. Specifically, we wanted to investigate the effect of architectural design variations on (1) model system failure loads when testing the individual materials either separately or homogeneously mixed, and (2) also evaluate the potential of modulating other mechanical properties of the model systems. Methods: Two sets of softer and harder biomaterials, 0.5% and 5% agarose vs. 0.5% agarose and gelatin, were used for fabrication. Architectural design variations were realized by varying ring geometries and amounts while keeping the material composition across designs comparable. Results: Variations in the architectural design, such as lamellar width, number, and order, combined with choosing specific biomaterial properties, strongly influenced the biomechanical performance of IVD constructs. Biomechanical characterization revealed that the single most important parameter, in which the model systems vastly exceeded those of the individual materials, was failure load. The model system failure loads were 32.21-and 84.11-fold higher than those of the agarose materials and 55.03-and 2.14-fold higher than those of the agarose and gelatin materials used for system fabrication. The compressive strength, dynamic stiffness, and viscoelasticity of the model systems were always in the range of the individual materials. Conclusions: Relevant architecture-promoted biomechanical performance-tuning of tissue-engineered constructs for biological IVD replacement can be realized by slight modifications in the design of constructs while preserving the materials’ compositions. Minimal variations in the architectural design can be used to precisely control structure–function relations for IVD constructs rather than choosing different materials. These fundamental findings have important implications for efficient tissue-engineering of IVDs and other load-bearing tissues, as potential implants need to withstand high in situ loads.
CRIS-Team Scopus Importer:2021-06-11
Keywords: 3R; Disc degeneration; Inflammation; Intervertebral disc; Regeneration; Spine; Tissue engineering

A review of glycosaminoglycan-modified electrically conductive polymers for biomedical applications - Schöbel, Lisa; Boccaccini, Aldo R. (Acta Biomaterialia, 2023)
The application areas of electrically conductive polymers have been steadily growing since their discovery in the late 1970s. Recently, electrically conductive polymers have found their way into biomedicine, allowing the realization of many relevant applications ranging from bioelectronics to scaffolds for tissue engineering. Extracellular matrix components, such as glycosaminoglycans, build an important class of biomaterials that are heavily researched for biomedical applications due to their favorable properties. Due to their highly anionic character and the presence of sulfate groups in glycosaminoglycans, these biomolecules can be employed to functionalize conductive polymers, which enables the tailorability and improvement of cell-material interactions of conductive polymers. This review paper gives an overview of recent research on glycosaminoglycan-modified conductive polymers intended for biomedical applications and discusses the effect of different biological dopants on material characteristics, such as surface roughness, stiffness, and electrochemical properties. Moreover, the key findings of the biological characterization in vitro and in vivo are summarized, and remaining challenges in the field, particularly related to the modification of electrically conductive polymers with glycosaminoglycans to achieve improved functional and biological outcomes, are discussed. Statement of significance: The development of functional biomaterials based on electrically conductive polymers (CPs) for various biomedical applications, such as neural regeneration, drug delivery, or bioelectronics, has been increasingly investigated over the last decades. Recent literature has shown that changes in the synthesis procedure or the chosen dopant could adjust the resulting material characteristics. Hence, an interesting approach lies in using natural biomolecules as dopants for CPs to tailor the biological outcome. This review comprehensively summarizes the state of the art in the field of glycosaminoglycan-modified electrically conductive polymers for the first time, particularly highlighting the effect of the chosen dopant on material characteristics, such as surface morphology or stiffness, electrochemical properties, and consequently, cell-material interactions.
CRIS-Team Scopus Importer:2023-09-22
Keywords: Biocompatibility; Electrically conductive polymers; Glycosaminoglycans; In vitro; In vivo

A review of hydrogel-based composites for biomedical applications: enhancement of hydrogel properties by addition of rigid inorganic fillers - Utech, Stefanie; Boccaccini, Aldo R. (Journal of Materials Science, 2016)
Abstract: There is a growing demand for three-dimensional scaffolds for expanding applications in regenerative medicine, tissue engineering, and cell culture techniques. The material requirements for such three-dimensional structures are as diverse as the applications themselves. A wide range of materials have been investigated in the recent decades in order to tackle these requirements and to stimulate the anticipated biological response. Among the most promising class of materials are inorganic/organic hydrogel composites for regenerative medicine. The generation of synergetic effects by hydrogel composite systems enables the design of materials with superior properties including biological performance, stiffness, and degradation behavior in vitro and in vivo. Here, we review the most important organic and inorganic materials used to fabricate hydrogel composites. We highlight the advantages of combining different materials with respect to their use for biofabrication and cell encapsulation as well as their application as injectable materials for tissue enhancement and regeneration. Graphical abstract: [Figure not available: see fulltext.]

A review of the biological response to ionic dissolution products from bioactive glasses and glass-ceramics - Hoppe, Alexander; Güldal, Nusret Sena; Boccaccini, Aldo R. (Biomaterials, 2011)
Several inorganic materials such as special compositions of silicate glasses, glass-ceramics and calcium phosphates have been shown to be bioactive and resorbable and to exhibit appropriate mechanical properties which make them suitable for bone tissue engineering applications. However, the exact mechanism of interaction between the ionic dissolution products of such inorganic materials and human cells are not fully understood, which has prompted considerable research work in the biomaterials community during the last decade. This review comprehensively covers literature reports which have investigated specifically the effect of dissolution products of silicate bioactive glasses and glass-ceramics in relation to osteogenesis and angiogenesis. Particularly, recent advances made in fabricating dense biomaterials and scaffolds doped with trace elements (e.g. Zn, Sr, Mg, and Cu) and investigations on the effect of these elements on the scaffold biological performance are summarized and discussed in detail. Clearly, the biological response to artificial materials depends on many parameters such as chemical composition, topography, porosity and grain size. This review, however, focuses only on the ion release kinetics of the materials and the specific effect of the released ionic dissolution products on human cell behaviour, providing also a scope for future investigations and identifying specific research needs to advance the field. The biological performance of pure and doped silicate glasses, phosphate based glasses with novel specific compositions as well as several other silicate based compounds are discussed in detail. Cells investigated in the reviewed articles include human osteoblastic and osteoclastic cells as well as endothelial cells and stem cells. © 2011 Elsevier Ltd.
UnivIS-Import:2015-03-09:Pub.2011.tech.IW.LM.arevie
Keywords: Bioactive glasses; Bioactivity; Bone tissue engineering; Cell proliferation; Metal ion release; Osteoblasts

A review on natural fiber-reinforced geopolymer and cement-based composites - Molano Camargo, Marfa Carolina; Taye, Eyerusalem; Roether, Judith; Redda, Daniel Tilahun; Boccaccini, Aldo R. (Materials, 2020)
The use of ecological materials for building and industrial applications contributes to minimizing the environmental impact of new technologies. In this context, the cement and geopolymer sectors are considering natural fibers as sustainable reinforcement for developing composites. Natural fibers are renewable, biodegradable, and non-toxic, and they exhibit attractive mechanical properties in comparison with their synthetic fiber counterparts. However, their hydrophilic character makes them vulnerable to high volumes of moisture absorption, thus conferring poor wetting with the matrix and weakening the fiber–matrix interface. Therefore, modification and functionalization strategies for natural fibers to tailor interface properties and to improve the durability and mechanical behavior of cement and geopolymer-based composites become highly important. This paper presents a review of the physical, chemical and biological pre-treatments that have been performed on natural fibers, their results and effects on the fiber–matrix interface of cement and geopolymer composites. In addition, the degradation mechanisms of natural fibers used in such composites are discussed. This review finalizes with concluding remarks and recommendations to be addressed through further in-depth studies in the field.
CRIS-Team Scopus Importer:2020-11-13
Keywords: Composites; Fibers; Geopolymers; Interphases; Surface treatments

Article synthesis and characterization of mesoporous mg-and sr-doped nanoparticles for moxifloxacin drug delivery in promising tissue engineering applications - Pouroutzidou, Georgia K.; Liverani, Liliana; Theocharidou, Anna; Tsamesidis, Ioannis; Lazaridou, Maria; Christodoulou, Evi; Beketova, Anastasia; Pappa, Christina; Triantafyllidis, Konstantinos S.; Anastasiou, Antonios D.; Papadopoulou, Lambrini; Bikiaris, Dimitrios N.; et al. (International Journal of Molecular Sciences, 2021)
Mesoporous silica-based nanoparticles (MSNs) are considered promising drug carriers because of their ordered pore structure, which permits high drug loading and release capacity. The dissolution of Si and Ca from MSNs can trigger osteogenic differentiation of stem cells towards extracellular matrix calcification, while Mg and Sr constitute key elements of bone biology and metabolism. The aim of this study was the synthesis and characterization of sol–gel-derived MSNs codoped with Ca, Mg and Sr. Their physico-chemical properties were investigated by X-ray diffraction (XRD), scanning electron microscopy with energy dispersive X-ray analysis (SEM/EDX), transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR), X-ray fluorescence spectroscopy (XRF), Brunauer Emmett Teller and Brunauer Joyner Halenda (BET/BJH), dynamic light scattering (DLS) and ζ-potential measurements. Moxifloxacin loading and release profiles were assessed with high performance liquid chromatography (HPLC) cell viability on human periodontal ligament fibroblasts and their hemolytic activity in contact with human red blood cells (RBCs) at various concentrations were also investigated. Doped MSNs generally retained their textural characteristics, while different compositions affected particle size, hemolytic activity and moxifloxacin loading/release profiles. All co-doped MSNs revealed the formation of hydroxycarbonate apatite on their surface after immersion in simulated body fluid (SBF) and promoted mitochondrial activity and cell proliferation.
CRIS-Team Scopus Importer:2021-01-22
Keywords: Drug loading/release; Human erythrocytes; Mesoporous nanoparticles; Moxifloxacin; Periodontal ligament cells

Artificial extracellular matrices containing bioactive glass nanoparticles promote osteogenic differentiation in human mesenchymal stem cells - Kroschwald, Lysann M.; Allerdt, Felix; Bernhardt, Anne; Rother, Sandra; Zheng, Kai; Maqsood, Iram; Halfter, Norbert; Heinemann, Christiane; Möller, Stephanie; Schnabelrauch, Matthias; Hacker, Michael C.; Rammelt, Stefan; et al. (International Journal of Molecular Sciences, 2021)
The present study analyzes the capacity of collagen (coll)/sulfated glycosaminoglycan (sGAG)‐based surface coatings containing bioactive glass nanoparticles (BGN) in promoting the osteogenic differentiation of human mesenchymal stroma cells (hMSC). Physicochemical characteristics of these coatings and their effects on proliferation and osteogenic differentiation of hMSC were investigated. BGN were stably incorporated into the artificial extracellular matrices (aECM). Oscillatory rheology showed predominantly elastic, gel‐like properties of the coatings. The complex viscosity increased depending on the GAG component and was further elevated by adding BGN. BGN‐containing aECM showed a release of silicon ions as well as an uptake of calcium ions. hMSC were able to proliferate on coll and coll/sGAG coatings, while cellular growth was delayed on aECM containing BGN. However, a stimulating effect of BGN on ALP activity and calcium deposition was shown. Furthermore, a synergistic effect of sGAG and BGN was found for some donors. Our findings demonstrated the promising potential of aECM and BGN combinations in promoting bone regeneration. Still, future work is required to further optimize the BGN/aECM combination for increasing its combined osteogenic effect.
CRIS-Team Scopus Importer:2021-12-17
Keywords: Artificial extracellular matrices; Bioactive glass nanoparticles; Glycosaminoglycans; Mesenchymal stem cells; Osteogenic differentiation

A self-assembled dynamic extracellular matrix-like hydrogel system with multi-scale structures for cell bioengineering applications - Xu, Yong; Rothe, Rebecca; Voigt, Dagmar; Sayed, Ahmed; Huang, Can; Hauser, Sandra; Lee, Pao Wan; Cui, Meiying; Sáenz, James P.; Boccaccini, Aldo R.; Zheng, Kai; Pietzsch, Jens; et al. (Acta Biomaterialia, 2023)
Extracellular matrix (ECM) provides various types of direct interactions with cells and a dynamic environment, which can be remodeled through different assembly/degradation mechanisms to adapt to different biological processes. Herein, through introducing polyphosphate-modified hyaluronic acid and bioactive glass (BG) nano-fibril into a self-assembled hydrogel system with peptide-polymer conjugate, we can realize many new ECM-like functions in a synthetic polymer network. The hydrogel network formation is mediated by coacervation, followed by a gradual transition of peptide structure from α-helix to β-sheet. The ECM-like hydrogels can be degraded through a number of orthogonal mechanisms, including treatments with protease, hyaluronidase, alkaline phosphatase, and calcium ion. As 2D coating, the ECM-like hydrogels can be used to modify the planar surface to promote the adhesion of mesenchymal stromal cells, or to coat the cell surface in a layer-by-layer fashion to shield the interaction with the substrate. As ECM-like hydrogels for 3D cell culture, the system is compatible with injection and cell encapsulation. Upon incorporating fragmented electrospun bioactive glass nano-fibril into the hydrogels, the synergetic effects of soft hydrogel and stiff reinforcement nanofibers on recapitulating ECM functions result in reduced cell circularity in 3D. Finally, by injecting the ECM-like hydrogels into mice, gradual degradations over a time period of one month and high biocompatibility have been shown in vivo. The contribution of complex network dynamics and hierarchical structures to cell-biomatrix interaction can be investigated multi-dimensionally, as many mechanisms are orthogonal to each other and can be regulated individually. Statement of significance: A list of native ECM features has attracted the most interest and attention in the research of synthetic biomaterials. In this research, we have described a simple ECM-like hydrogel system in which the complex and elegant functions of native ECM can be recapitulated in a chemically defined synthetic system. The ECM-like hydrogel systems were developed to avoid undesired features of biological substances (e.g., ethical concerns, batch-to-batch variation, immunogenicity, and potential risk of contamination), as well as gaining new functions to facilitate bioengineering applications (e.g., 3D cell culture, injection, and high stability). To this end, we have developed an ECM-like hydrogel system and provide evidence that this purely synthetic biomaterial is a promising candidate for cell bioengineering applications.
CRIS-Team Scopus Importer:2023-04-14
Keywords: Bioactive glass fiber; Cell-coating; Coacervation; Extracellular matrix; Injectable hydrogel

A Self-Assembled Matrix System for Cell-Bioengineering Applications in Different Dimensions, Scales, and Geometries - Xu, Yong; Gaillez, Michelle Patino; Zheng, Kai; Voigt, Dagmar; Cui, Meiying; Kurth, Thomas; Xiao, Lingfei; Rothe, Rebecca; Hauser, Sandra; Lee, Pao-Wan; Wieduwild, Robert; Lin, Weilin; et al. (Small, 2022)
Stem cell bioengineering and therapy require different model systems and materials in different stages of development. If a chemically defined biomatrix system can fulfill most tasks, it can minimize the discrepancy among various setups. By screening biomaterials synthesized through a coacervation-mediated self-assembling mechanism, a biomatrix system optimal for 2D human mesenchymal stromal cell (hMSC) culture and osteogenesis is identified. Its utility for hMSC bioengineering is further demonstrated in coating porous bioactive glass scaffolds and nanoparticle synthesis for esiRNA delivery to knock down the SOX-9 gene with high delivery efficiency. The self-assembled injectable system is further utilized for 3D cell culture, segregated co-culture of hMSC with human umbilical vein endothelial cells (HUVEC) as an angiogenesis model, and 3D bioprinting. Most interestingly, the coating of bioactive glass with the self-assembled biomatrix not only supports the proliferation and osteogenesis of hMSC in the 3D scaffold but also induces the amorphous bioactive glass (BG) scaffold surface to form new apatite crystals resembling bone-shaped plate structures. Thus, the self-assembled biomatrix system can be utilized in various dimensions, scales, and geometries for many different bioengineering applications.
CRIS-Team WoS Importer:2022-02-18

A shelf-life study of silica- and carbon-based mesoporous materials - Björk, Emma M.; Atakan, Aylin; Wu, Pei Hsuan; Bari, Alessandra; Pontremoli, Carlotta; Zheng, Kai; Giasafaki, Dimitra; Iviglia, Giorgio; Torre, Elisa; Cassinelli, Clara; Morra, Marco; Steriotis, Theodore; et al. (Journal of Industrial and Engineering Chemistry, 2021)
Mesoporous silica- and carbon-based materials, including bioactive glasses, have proven potential as components of medical devices and as drug carriers. From an application perspective, knowledge about the shelf-life stability of these materials under various conditions is vital. Here, mesoporous bioactive glasses (MBGs) synthesized by aerosol-assisted spray-drying and by a batch sol–gel method, mesoporous silicas of SBA-15 type, and mesoporous carbons CMK-1 and CMK-3 have been stored under varying conditions, e.g. at different temperature and relative humidity (RH), and in different storage vessels. The results show that the silica-based materials stored in Eppendorfs are sensitive to humidity. Spray dried MBGs decompose within 1 month at a RH >5%, whilst sol–gel MBGs are more stable up to a RH >60%. Changing the storage vessel to sealed glass flasks increases the MBGs lifetime significantly, with no degradation during 2 months of storage at a RH = 75%. SBA-15 stored in Eppendorfs are more stable compared to MBGs, and addition of F- ions added during the synthesis affects the material degradation rate. Mesoporous carbons are stable under all conditions for all time points. This systematic study clearly demonstrates the importance of storage conditions for mesoporous materials which is crucial knowledge for commercialization of these materials.
CRIS-Team Scopus Importer:2021-08-06
Keywords: Materials stability; Mesoporous bioactive glass; Mesoporous carbon; Mesoporous silica; Shelf-life

Ash from sunflower husk as raw material for ceramic products - Boccaccini, Aldo R.; et al. (Ceramics International, 2010)
UnivIS-Import:2015-03-09:Pub.2010.tech.IW.LM.ashfro

Aspirin-loaded P(3HO)/P(3HB) blend films: potential materials for biodegradable drug-eluting stents - Basnett, Pooja; Ching, Kuan Yong; Stolz, Martin; Knowles, Jonathan C.; Boccaccini, Aldo R.; Smith, Caroline; Locke, Ian C.; Roy, Ipsita (Bioinspired, Biomimetic and Nanobiomaterials, 2013)
UnivIS-Import:2015-03-09:Pub.2013.tech.IW.LM.youory

Assessment of cardiac patches suitability for tissue engineering - Madeddu, D.; Falco, A.; Frati, C.; Graiani, G.; Gervasi, A.; Lorusso, B.; Rosellini, E.; Rai, Ranjana; Boccaccini, Aldo R.; Lagrasta, C.; Quaini, F. (Vascular Pharmacology, 2015)

Assessment of cellular toxicity of TiO2 nanoparticles for cardiac tissue engineering applications - Jawad, Hedeer; Boccaccini, Aldo R.; Ali, Nadire N.; Harding, Sian E. (Nanotoxicology, 2010)
UnivIS-Import:2015-03-09:Pub.2010.tech.IW.LM.assess_9

Assessment of in-vitro bioactivity, biodegradability and antibacterial activity of polymer-derived 3D printed åkermanite scaffolds - Dogrul, Fulden; Bednarzig, Vera; Elsayed, Hamada; Liverani, Liliana; Galusek, Dušan; Bernardo, Enrico; Boccaccini, Aldo R. (Open Ceramics, 2023)
Reticulated åkermanite (Ca2MgSi2O7) 3D scaffolds were fabricated by direct ink writing of pastes based on a commercial silicone resin and fillers, such as calcium carbonate (CaCO3) and magnesium hydroxide (Mg(OH)2) microparticles, followed by heat treatment at 1100 °C in air. To form liquid phase upon firing and thus promote the ionic interdiffusion, borax (Na2B4O7·10H2O) or hydrated sodium phosphate (Na2HPO4·12H2O) were considered as alternative additives. Although leading to scaffolds with different strength-to-density ratio, the two additives did not lead to substantial differences in terms of biological response. All fabricated ceramics exhibited acellular in-vitro bioactivity upon immersion in simulated-body-fluid (SBF) as well as antibacterial activity against S. aureus and E. coli. Direct contact cell viability test, performed with a stromal-cell line from mouse bone marrow (ST-2 cells), indicated no cytotoxicity of both samples determined by the WST-8 assay.
CRIS-Team Scopus Importer:2023-08-11
Keywords: Antibacterial activity; Bioactivity; Bioceramic; Cytocompatibility; Direct ink writing (DIW); Polymer-derived-ceramic; Scaffold; Åkermanite

Assessment of in vitro testing approaches for bioactive inorganic materials - Rohanova, Dana; Horkavcova, Diana; Helebrant, Ales; Boccaccini, Aldo R. (Journal of Non-Crystalline Solids, 2016)
This paper deals with non-standard in vitro testing of bioactive inorganic materials shaped as granules or scaffolds. The ISO 23317 standard describes the in vitro test arrangement of bulk bioactive materials under static conditions. However, this norm has not dealt with bioactive materials shaped as granules (with large surface area) that are commonly used in clinical practice. We found that in the case of highly reactive (bioactive) materials, the biogenic elements were exhausted from simulated body fluid (SBF) solution very quickly (within hours) under static conditions. In such exhausted SBF solution the formation of Ca-P layer (hydroxyapatite - HAp) was stopped in agreement with the decrease of Ca and P concentrations. On the contrary, highly soluble materials (glass-ceramic scaffold) induced the formation of a new mineral layer also on the walls of the PE container used. For a non-standard shape of the tested materials the usage of dynamic or static-dynamic in vitro test arrangement was confirmed to be a better option to test bioactivity. However, also for this type of arrangement it is essential to determine the S/V or S/F ratios (the surface area/volume or flow of SBF solution) very precisely. For detailed understanding of the interaction between the tested material and SBF it is important to analyze the leachates (monitoring Ca, (PO) and minor element concentrations) and to monitor the pH value. An expected result of the in vitro test (according ISO standard) is the formation of HAp on the surfaces of tested samples in SBF. However, the formation of hydroxyapatite may not be the proof of their potential bioactivity necessarily (e.g. due to the use of TRIS buffer).
Keywords: Biomaterial; Dynamic arrangement; Hydroxyapatite; In vitro test; SBF

A statistical approach for the assessment of reliability in ceramic materials from ultrasonic velocity measurement: Cumulative Flaw Length Theory - Boccaccini, D. N.; Maioli, M.; Cannio, M.; Romagnoli, Marcello; Veronesi, Paolo; Leonelli, Cristina; Boccaccini, Aldo R. (Engineering Fracture Mechanics, 2009)
A primary objective of statistical fracture approach is to predict the probability of failure of a component for an arbitrary stress state when the failure statistics are known. This study introduces the fundamentals and application of a new approach to characterize the mechanical behaviour of high temperature ceramic materials, including refractory materials, by coupling non-destructive methods, in particular ultrasonic velocity measurement, and the Batdorf statistical fracture theory. A new approach, termed Cumulative Flaw Length Theory (CFLT), has been developed for the case of macroscopically homogeneous isotropic materials containing randomly oriented microcracks uniformly distributed in a location subjected to non-uniform multiaxial stresses. A function representing the number of cracks per unit volume is estimated based on the histograms of ultrasonic velocity measurements. This function is used without additional assumptions to determine the probability of fracture under an arbitrary stress condition. Two different cordierite-mullite high temperature ceramic materials were characterized under the assumptions of this theory to provide experimental evidence to support the model. © 2009 Elsevier Ltd. All rights reserved.
UnivIS-Import:2015-03-09:Pub.2009.tech.IW.LM.astati
Keywords: Batdorf theory; Failure probability; Fracture mechanics; Non-destructive testing; Ultrasonic velocity

A structural comparison of ordered and non-ordered ion doped silicate bioactive glasses - Schmitz, Seray; Beltrán, Ana M.; Cresswell, Mark; Boccaccini, Aldo R. (Materials, 2020)
One of the key benefits of sol-gel-derived glasses is the presence of a mesoporous structure and the resulting increase in surface area. This enhancement in textural properties has a significant effect on the physicochemical properties of the materials. In this context the aim of this study was to investigate how sol-gel synthesis parameters can influence the textural and structural properties of mesoporous silicate glasses. We report the synthesis and characterization of metal ion doped sol-gel derived glasses with different dopants in the presence or absence of a surfactant (Pluronic P123) used as structure-directing templating agent. Characterization was done by several methods. Using a structure directing agent led to larger surface areas and highly ordered mesoporous structures. The chemical structure of the non-ordered glasses was modified to a larger extent than the one of the ordered glasses due to increased incorporation of dopant ions into the glass network. The results will help to further understand how the properties of sol-gel glasses can be controlled by incorporation of metal dopants, in conjunction with control over the textural properties, and will be important to optimize the properties of sol-gel glasses for specific applications, e.g., drug delivery, bone regeneration, wound healing, and antibacterial materials.
CRIS-Team Scopus Importer:2020-03-31
Keywords: Bioactive glass; Mesoporous; Non-ordered; Ordered; Sol-gel method

A study of the electrophoretic deposition of Bioglass® suspensions using the Taguchi experimental design approach - Pishbin, F.; Simchi, Abdolreza; Ryan, M. P.; Boccaccini, Aldo R. (Journal of the European Ceramic Society, 2010)
This paper presents a study of the Taguchi design method to optimise the rate of electrophoretic deposition (EPD) of Bioglass® particles from aqueous suspensions. The effect of Bioglass® concentration, pH and electric field was investigated. An orthogonal array of L16 type with mixed levels of the control factors was utilized. Multivariate analysis of variance (MANOVA) and regression analysis based on the partial least-square method were used to identify the significant factors affecting the deposition rate and its stability during constant-voltage EPD. It was found that the pH of the suspension significantly influences the deposition rate whereas the applied electric field has the smallest effect on the deposition rate. In addition, the interaction between the Bioglass® concentration and pH, which are key processing parameters influencing the deposition rate, was found to be significant. Although a high deposition rate was obtained at low electric field (5V/cm) and pH 7, the instability of the suspension in particular at high Bioglass® concentrations resulted in an increase in the variability of the deposition rate. The optimal EPD condition predicted was verified by experiments and good qualitative agreement was obtained. The experimental results and statistical analyses are discussed based on the current knowledge of the EPD of ceramic materials. © 2010 Elsevier Ltd.
UnivIS-Import:2015-03-09:Pub.2010.tech.IW.LM.astudy
Keywords: Bioglass; Coating; Electrophoretic deposition; Taguchi design

A two-scale model for simultaneous sintering and crystallization of glass-ceramic scaffolds for tissue engineering - Huang, R.; Pan, J.; Boccaccini, Aldo R.; Chen, Q. Z. (Acta Biomaterialia, 2008)
Bioglass®-based glass-ceramic foams have been developed recently as highly porous, mechanically competent, bioactive and degradable scaffolds for bone tissue engineering. However, the development of the material so far has been based on a trial-and-error approach, and the existing materials are far from being optimized. In this paper, a mechanism-based model is presented for sintering deformation of Bioglass® foams. The porous foams consist of struts which, in turn, consist of Bioglass® particles. A corresponding two-scale model is developed based on existing viscous sintering models. Crystallization plays a key role in the sintering deformation of Bioglass® foams and is taken into account in the model. Qualitative comparison between the model predictions and experimental observations is presented, showing that the model is able to capture the complicated interplay between crystallization and viscous flow during the sintering process. © 2008 Acta Materialia Inc.
UnivIS-Import:2015-03-09:Pub.2008.tech.IW.LM.atwosc
Keywords: Bioactive glass; Crystallization; Model; Sintering

A unified in vitro evaluation for apatite-forming ability of bioactive glasses and their variants - Macon, Anthony L. B.; Kim, Taek B.; Valliant, Esther M.; Goetschius, Kathryn; Brow, Richard K.; Day, Delbert E.; Hoppe, Alexander; Boccaccini, Aldo R.; Kim, Ill Yong; Ohtsuki, Chikara; Kokubo, Tadashi; Osaka, Akiyoshi; et al. (Journal of Materials Science: Materials in Medicine, 2015)
The aim of this study was to propose and validate a new unified method for testing dissolution rates of bioactive glasses and their variants, and the formation of calcium phosphate layer formation on their surface, which is an indicator of bioactivity. At present, comparison in the literature is difficult as many groups use different testing protocols. An ISO standard covers the use of simulated body fluid on standard shape materials but it does not take into account that bioactive glasses can have very different specific surface areas, as for glass powders. Validation of the proposed modified test was through round robin testing and comparison to the ISO standard where appropriate. The proposed test uses fixed mass per solution volume ratio and agitated solution. The round robin study showed differences in hydroxyapatite nucleation on glasses of different composition and between glasses of the same composition but different particle size. The results were reproducible between research facilities. Researchers should use this method when testing new glasses, or their variants, to enable comparison between the literature in the future.

Behavior of encapsulated MG-63 cells in RGD and gelatine-modified alginate hydrogels - Grigore, Alexandra; Sarker, Bapi; Fabry, Ben; Boccaccini, Aldo R.; Detsch, Rainer (Tissue Engineering - Part A, 2014)
Achieving cell spreading and proliferation inside hydrogels that are compatible with microencapsulation technology represents a major challenge for tissue engineering scaffolding and for the development of three-dimensional cell culture models. In this study, microcapsules of 650-900μm in diameter were fabricated from oxidized alginate covalently cross-linked with gelatine (AlGel). Schiff's base bond formed in AlGel, detected by Fourier transform infrared spectroscopy, which confirmed the cross-linking of oxidized alginate with gelatine. Biological properties of alginate based hydrogels were studied by comparing the viability and morphology of MG-63 osteosarcoma cells encapsulated in gelatine and RGD-modified alginate. We hypothesized that the presence of gelatine and RGD will support cell adhesion and spreading inside the microcapsules and finally, also vascular endothelial growth factor (VEGF) secretion. After 4 days of incubation, cells formed extensive cortical protrusions and after 2 weeks they proliferated, migrated, and formed cellular networks through the AlGel material. In contrast, cells encapsulated in pure alginate and in RGD-modified alginate formed spherical aggregates with limited cell mobility and VEGF secretion. Metabolic activity was doubled after 5 days of incubation, making AlGel a promising material for cell encapsulation. © Mary Ann Liebert, Inc.

Bilayered bioactive glass scaffolds incorporating fibrous morphology by flock technology - Balasubramanian, Preethi; Boccaccini, Aldo R. (Materials Letters, 2015)
We report for the first time on the combination of polymer replication method and flock technology to produce 45S5 bioactive glass (45S5 BG) scaffolds with a fibrous surface morphology suitable for tissue engineering (TE). In order to develop a fibrous morphology on the surface of the scaffolds, electroflocking was used with BG scaffolds serving as the substrate. Gelatin was used as the adhesive and short polyamide (PA) fibers were electroflocked on the top surface to produce scaffolds with anisotropic properties. In order to improve the stability of the adhesive (gelatin) and to create a better bonding between the fibers and the adhesive, a crosslinking step was carried out. The porosity on the surface could be tailored by varying the flocking time which, in turn, was shown to influence the packing density of the fibers. In vitro bioactivity study in simulated body fluid (SBF) was carried out and complete mineralization of the scaffold, including on the PA fibers, was detected and characterized using various techniques.
Keywords: Bioglass; Electroflocking; Osteochondral tissue engineering; Scaffold fabrication

Bi-layered porous constructs of PCL-coated 45S5 bioactive glass and electrospun collagen-PCL fibers - Balasubramanian, Preethi; Roether, Judith; Schubert, Dirk W.; Beier, Justus; Boccaccini, Aldo R. (Journal of Porous Materials, 2015)
A simple yet promising approach to construct bi-layered scaffolds using bioactive ceramics and biodegradable polymers is presented. This method involves two versatile fabrication techniques used in the field of TE: foam replication process and electrospinning. By the foam replication method, three-dimensional 45S5 bioactive glass (BG)-based scaffolds with high porosity, in the range of 95.8 ± 0.9 %, were produced. To improve the mechanical properties of the BG scaffolds, dip-coating using polycaprolactone (PCL) was performed, which led to a significant increase in the compressive strength of the scaffolds. In order to develop a bi-layered construct, bead-less submicrometric fibers of collagen-PCL were electrospun over the PCL-coated BG scaffolds. Surface morphology, surface properties and mechanical strength of the bi-layered construct were evaluated using scanning electron microscopy analysis, contact angle measurements and compressive strength testing, respectively. In vitro degradation of the collagen-PCL fibers in phosphate buffered saline and in vitro bioactivity of the bi-layered constructs in simulated body fluid were investigated. Formation of hydroxyapatite on the PCL-coated BG and along the morphology of the collagen-PCL fibers was ascertained using different characterization techniques. The bi-layered construct is intended for interface tissue engineering applications where the PCL-coated BG scaffold, which is highly bioactive, can serve as a support for the bone side and the composite collagen-PCL submicrometric fibers are intended for the cartilage side.
Keywords: Bioactivity; Electrospinning; In vitro degradation; Osteochondral region; Scaffold

Bioactivation of titanium dioxide scaffolds by ALP-functionalization - Sengottuvelan, Abirami; Balasubramanian, Preethi; Will, Julia; Boccaccini, Aldo R. (Bioactive Materials, 2017)

Bioactive and Antibacterial Coatings Based on Zein/Bioactive Glass Composites by Electrophoretic Deposition - Meyer, Nima; Ramos Rivera, Laura; Ellis, Tim; Qi, Jiahui; Ryan, Mary P.; Boccaccini, Aldo R. (Coatings, 2018)

Bioactive and biodegradable polymer-based composites - Gritsch, Lukas; Boccaccini, Aldo R. (Elsevier, 2021)
CRIS-Team Scopus Importer:2021-11-19

Bioactive behavior of mesoporous silica particle (MCM-41) coated bioactive glass-based scaffolds - Boccardi, Elena; Liverani, Liliana; Boccaccini, Aldo R. (International Journal of Applied Ceramic Technology, 2019)
A complete characterization of a novel family of multifunctional bioactive glass (45S5 composition) (BG)-based scaffolds for bone tissue engineering is presented. Scaffolds were developed via replication method of polyurethane packaging foam and natural marine sponge “Spongia Agaricina”. In order to increase the therapeutic functionality, the scaffolds were coated with mesoporous silica particles (MCM-41), which can act as drug delivery carrier, increase the bioactivity of the combined system and release Si ions, essential for the gene stimulation of osteoblast cells and for inducing new bone matrix formation. The MCM-41 particles were synthetized directly inside the scaffolds (CCM) or after the synthesis they were dispersed in ethanol and used for impregnation (PCM) of the scaffolds. The effect of the particles on the bioactivity of the scaffolds was assessed in simulated body fluid (SBF) for up to 7 days. The results indicate the possibility to obtain a multifunctional BG-scaffold system with enhanced bioactivity and reduced pH increase when in contact with physiological fluids.
CRIS-Team Scopus Importer:2019-05-02
Keywords: bioactive glass; bioactivity; scaffold

Bioactive Carbon-Based Hybrid 3D Scaffolds for Osteoblast Growth - Taale, Mohammadreza; Schuett, Fabian; Zheng, Kai; Mishra, Yogendra Kumar; Boccaccini, Aldo R.; Adelung, Rainer; Selhuber-Unkel, Christine (ACS Applied Materials and Interfaces, 2018)
Keywords: hydroxyapatite; osteoblasts; 3D scaffolds; carbon nanotubes; bioactive glass

Bioactive coating of zirconia toughened alumina ceramic implants improves cancellous osseointegration - Pobloth, Anne Marie; Mersiowsky, Max J.; Kliemt, Luisa; Schell, Hanna; Dienelt, Anke; Pfitzner, Berit M.; Burgkart, Rainer; Detsch, Rainer; Wulsten, Dag; Boccaccini, Aldo R.; Duda, Georg N. (Scientific Reports, 2019)
Bioactive coatings have the potential to improve the bony integration of mechanically loaded orthopedic ceramic implants. Using the concept of mimicking the natural bone surface, four different coatings of varying thickness on a zirconia toughened alumina (ZTA) ceramic implant were investigated regarding their osseointegration in a drill-hole model in sheep. The hypothesis that a bioactive coating of ZTA ceramics would facilitate cancellous bone integration was investigated. The bioactive coatings consisted of either a layer of covalently bound multi phosphonate molecules (chemical modification = CM), a nano hydoxyapatite coating (HA), or two different bioactive glass (BG) coatings in micrometer thickness, forming a hydroxyl-carbonate apatite layer on the implant surface in vivo (dip-coated 45S5 = DipBG; sol-gel 70S30C = SGBG). Coated surfaces were characterized by scanning electron microscopy and X-ray photoelectron spectroscopy. After 12 weeks, osseointegration was evaluated via mechanical push-out testing and histology. HA enhanced the maximum push-out force (HA: mean 3573.85 ± 1119.91 N; SGBG: mean 1691.57 ± 986.76 N; p = 0.046), adhesive shear strength (HA: mean 9.82 ± 2.89 MPA; SGBG: mean 4.57 ± 2.65 MPA; p = 0.025), and energy release rate (HA: mean 3821.95 ± 1474.13 J/mm2; SGBG: mean 1558.47 ± 923.47 J/mm2; p = 0.032) compared to SGBG. The implant-bone interfacial stiffness increased by CM compared to SGBG coating (CM: mean 6258.06 ± 603.80 N/mm; SGBG: mean 3565.57 ± 1705.31 n/mm; p = 0.038). Reduced mechanical osseointegration of SGBG coated implants could be explained histologically by a foreign body reaction surrounding the implants.
CRIS-Team Scopus Importer:2019-11-22

Bioactive coatings on porous titanium for biomedical applications - Dominguez-Trujillo, C.; Ternero, F.; Rodriguez-Ortiz, J. A.; Heise, Svenja; Boccaccini, Aldo R.; Lebrato, Julian; Torres, Y. (Surface & Coatings Technology, 2018)
Keywords: Hydroxyapatite; In vitro bioactivity; Bioactive glass coating; Stress-shielding; Osseointegration; Porous titanium

Bioactive copper-doped glass scaffolds can stimulate endothelial cells in co-culture in combination with mesenchymal stem cells - Rath, Subha N.; Brandl, Andreas; Hiller, Daniel; Hoppe, Alexander; Gbureck, Uwe; Horch, Raymund E.; Boccaccini, Aldo R.; Kneser, Ulrich (PLoS ONE, 2014)
Bioactive glass (BG) scaffolds are being investigated for bone tissue engineering applications because of their osteoconductive and angiogenic nature. However, to increase the in vivo performance of the scaffold, including enhancing the angiogenetic growth into the scaffolds, some researchers use different modifications of the scaffold including addition of inorganic ionic components to the basic BG composition. In this study, we investigated the in vitro biocompatibility and bioactivity of Cu-doped BG derived scaffolds in either BMSC (bone-marrow derived mesenchymal stem cells)-only culture or co-culture of BMSC and human dermal microvascular endothelial cells (HDMEC). In BMSC-only culture, cells were seeded either directly on the scaffolds (3D or direct culture) or were exposed to ionic dissolution products of the BG scaffolds, kept in permeable cell culture inserts (2D or indirect culture). Though we did not observe any direct osteoinduction of BMSCs by alkaline phosphatase (ALP) assay or by PCR, there was increased vascular endothelial growth factor (VEGF) expression, observed by PCR and ELISA assays. Additionally, the scaffolds showed no toxicity to BMSCs and there were healthy live cells found throughout the scaffold. To analyze further the reasons behind the increased VEGF expression and to exploit the benefits of the finding, we used the indirect method with HDMECs in culture plastic and Cu-doped BG scaffolds with or without BMSCs in cell culture inserts. There was clear observation of increased endothelial markers by both FACS analysis and acetylated LDL (acLDL) uptake assay. Only in presence of Cu-doped BG scaffolds with BMSCs, a high VEGF secretion was demonstrated by ELISA; and typical tubular structures were observed in culture plastics. We conclude that Cu-doped BG scaffolds release Cu, which in turn act on BMSCs to secrete VEGF. This result is of significance for the application of BG scaffolds in bone tissue engineering approaches.

Bioactive dental materials-Do they exist and what does bioactivity mean? - Vallittu, Pekka K.; Boccaccini, Aldo R.; Hupa, Leena; Watts, David C. (Dental Materials, 2018)

Bioactive Electrospun Fibers of Poly(glycerol sebacate) and Poly(ε-caprolactone) for Cardiac Patch Application - Rai, Ranjana; Tallawi, Marwa; Frati, Caterina; Falco, Angela; Gervasi, Andrea; Quaini, Federico; Roether, Judith; Hochburger, Tobias; Schubert, Dirk W.; Seik, Lothar; Barbani, Niccoletta; Lazzeri, Luigi; et al. (Advanced Healthcare Materials, 2015)
Scaffolds for cardiac patch application must meet stringent requirements such as biocompatibility, biodegradability, and facilitate vascularization in the engineered tissue. Here, a bioactive, biocompatible, and biodegradable electrospun scaffold of poly(glycerol sebacate)–poly(ε-caprolactone) (PGS–PCL) is proposed as a potential scaffold for cardiac patch application. The fibers are smooth bead free with average diameter = 0.8 ± 0.3 μm, mean pore size = 2.2 ± 1.2 μm, porosity = 62 ± 4%, and permeability higher than that of control biological tissue. For the first time, bioactive PGS–PCL fibers functionalized with vascular endothelial growth factor (VEGF) are developed, the approach used being chemical modification of the PGS–PCL fibers followed by subsequent binding of VEGF via amide bonding. The approach results in uniform immobilization of VEGF on the fibers; the concentrations are 1.0 μg cm−2 for the PGS–PCL (H) and 0.60 μg cm−2 for the PGS–PCL (L) samples. The bioactive scaffold supports the attachment and growth of seeded myogenic and vasculogenic cell lines. In fact, rat aortic endothelial cells also display angiogenic features indicating potential for the formation of vascular tree in the scaffold. These results therefore demonstrate the prospects of VEGF-functionalized PGS–PCL fibrous scaffold as promising matrix for cardiac patch application.

Bioactive glass (45S5)-based 3D scaffolds coated with magnesium and zinc-loaded hydroxyapatite nanoparticles for tissue engineering applications - Dittler, Maria Laura; Ünalan, Irem; Grünewald, Alina; Beltrán, Ana M.; Grillo, Claudia A.; Detsch, Rainer; Gonzalez, Monica C.; Boccaccini, Aldo R. (Colloids and Surfaces B: Biointerfaces, 2019)
Bioactive glass (BG)-based scaffolds of 45S5 composition covered with hydroxyapatite nanoparticles loaded with Mg2+, Zn2+ and, both Mg2+ and Zn2+ ions, were developed and tested as materials for tissue engineering applications. The scaffolds were prepared by the foam replica technique and mono- and bi-metal loaded and unloaded hydroxyapatite nanoparticles (HA, Zn-HA, Mg-HA and Mg-Zn-HA) were obtained by an adaptation of the wet chemical deposition method. Coating of BG with these nanoparticles was performed by dip-coating to obtain HA-BG, Zn-HA-BG, Mg-HA-BG and Mg-Zn-HA-BG scaffolds. As predictor of the bone bonding ability of the produced scaffolds, in this study we investigated the formation of an apatite layer on the scaffold surfaces in the presence of simulated body fluid. The cytotoxicity and osteogenic properties of the materials in vitro was evaluated using human osteoblast-like MG-63 cell cultures. The mineralization assay following Kokubo's protocol indicated that bi-metal loaded Mg-Zn-HA-BG scaffolds exhibited higher/faster bioactivity than mono-metal loaded scaffolds while mineralization of HA-BG, Zn-HA-BG and Mg-HA-BG was similar to that of uncoated scaffolds. Moreover, an increase of proliferation of MG-63 cells after 48 h and 7 days was measured by BrdU assays for Mg-Zn-HA-BG scaffolds. In agreement with these results, SEM images confirmed increased interaction between these scaffolds and cells, in comparison to that observed for mono-metal-loaded HA-coated scaffolds. Altogether, the obtained results suggest that nanocrystalline Mg-Zn-HA coatings enhance the biological performance of standard scaffolds of 45S5 BG composition. Thus these novel ion doped HA coated scaffolds are attractive systems for bone tissue engineering.
CRIS-Team Scopus Importer:2019-07-23
Keywords: Bioactive glass (45S5); Biological performance; Bone tissue engineering; Mg- loaded hydroxyapatite nanoparticles; MG-63 cells; Scaffolds; Zn and Mg bi-metal loaded hydroxyapatite; Zn- loaded hydroxyapatite nanoparticles

Bioactive Glass and Silica Particles for Skeletal and Cardiac Muscle Tissue Regeneration - Ege, Duygu; Lu, Hsuan-Heng; Boccaccini, Aldo R. (Tissue Engineering - Part B: Reviews, 2024)
When skeletal and cardiac tissues are damaged, surgical approaches are not always successful and tissue regeneration approaches are investigated. Reports in the literature indicate that silica nanoparticles and bioactive glasses (BGs), including silicate bioactive glasses (e.g., 45S5 BG), phosphate glass fibers, boron-doped mesoporous BGs, borosilicate glasses, and aluminoborates, are promising for repairing skeletal muscle tissue. Silica nanoparticles and BGs have been combined with polymers to obtain aligned nanofibers and to maintain controlled delivery of nanoparticles for skeletal muscle repair. The literature indicates that cardiac muscle regeneration can be also triggered by the ionic products of BGs. This was observed to be due to the release of vascular endothelial growth factor and other growth factors from cardiomyocytes, which regulate endothelial cells to form capillary structures (angiogenesis). Specific studies, including both in vitro and in vivo approaches, are reviewed in this article. The analysis of the literature indicates that although the research field is still very limited, BGs are showing great promise for muscle tissue engineering and further research in the field should be carried out to expand our basic knowledge on the application of BGs in muscle (skeletal and cardiac) tissue regeneration.
CRIS-Team Scopus Importer:2024-03-08
Keywords: bioactive glass; borate glass; cardiac muscle; phosphate glasses; silica nanoparticles; skeletal muscle

Bioactive glass-based fibrous wound dressings - Homaeigohar, Shahin; Li, Meng; Boccaccini, Aldo R. (Burns & Trauma, 2022)
Since the discovery of silicate bioactive glass (BG) by Larry Hench in 1969, different classes of BGs have been researched over decades mainly for bone regeneration. More recently, validating the beneficial influence of BGs with tailored compositions on angiogenesis, immunogenicity and bacterial infection, the applicability of BGs has been extended to soft tissue repair and wound healing. Particularly, fibrous wound dressings comprising BG particle reinforced polymer nanofibers and cotton-candy-like BG fibers have been proven to be successful for wound healing applications. Such fibrous dressing materials imitate the physical structure of skin's extracellular matrix and release biologically active ions e.g. regenerative, pro-angiogenic and antibacterial ions, e.g. borate, copper, zinc, etc., that can provoke cellular activities to regenerate the lost skin tissue and to induce new vessels formation, while keeping an anti-infection environment. In the current review, we discuss different BG fibrous materials meant for wound healing applications and cover the relevant literature in the past decade. The production methods for BG-containing fibers are explained and as fibrous wound dressing materials, their wound healing and bactericidal mechanisms, depending on the ions they release, are discussed. The present gaps in this research area are highlighted and new strategies to address them are suggested.
CRIS-Team WoS Importer:2022-10-21

Bioactive glass based scaffolds coated with gelatin for the sustained release of icariin. - Reiter, Theresa; Panick, Tanja; Schuhladen, Katharina; Roether, Judith; Hum, Jasmin; Boccaccini, Aldo R. (Bioactive Materials, 2019)
Gelatin-coated, 3D sponge-like scaffolds based on 45S5 bioactive glass were produced using the foam replication technique. Compressive strength tests of gelatin-coated samples compared to uncoated scaffolds showed significant strengthening and toughening effects of the gelatin coating with compressive strength values in the range of cortical bone. Additionally, the crosslinked gelatin network (using either caffeic acid or N-(3-Dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (EDC)/N-hxdroxysuccinimide (NHS) as crosslinking agent) was shown to be a suitable candidate for the sustained release of the bioactive molecule icariin. Concerning bioactivity of the produced scaffolds, characterization by FTIR and SEM indicated the formation of hydroxyapatite (HA) in all samples after immersion in simulated body fluid (SBF) for 14 days, highlighting the favorable combination of mechanical robustness, bioactivity and drug delivery capability of this new type of scaffolds.

Bioactive Glass-Based Scaffolds for Bone Tissue Engineering - Gerhardt, Lutz-Christian; Boccaccini, Aldo R. (Materials, 2010)
UnivIS-Import:2015-03-09:Pub.2010.tech.IW.LM.bioact

Bioactive glass based scaffolds incorporating gelatin/manganese doped mesoporous bioactive glass nanoparticle coating - Nawaz, Qaisar; Ur Rehman, Muhammad Atiq; Roether, Judith; Yufei, Liu; Grünewald, Alina; Detsch, Rainer; Boccaccini, Aldo R. (Ceramics International, 2019)
We investigated the bioactivity and cytocompatibility of 45S5 bioactive glass (BG) based scaffolds coated with a composite layer formed by gelatin and manganese doped mesoporous bioactive glass nanoparticles (Mn-MBGNs). The scaffolds were prepared using the foam replica method, and they were further coated with Mn-MBGNs/gelatin via dip coating. The synthesized scaffolds were characterized in relation to morphology, porosity, mechanical stability, bioactivity and cell biology behavior using osteoblast-like (MG-63) cells. The scaffolds were highly porous with interconnected porosity, and a suitable pore structure was maintained even after the Mn-MBGNs/gelatin coating. Energy-dispersive X-ray spectroscopy (EDX) confirmed the presence of Mn-MBGNs in the coatings. Moreover, the presence of gelatin was confirmed by Fourier transform infrared spectroscopy (FTIR). The coated scaffolds exhibited in-vitro bioactivity in simulated body fluid comparable to that of uncoated BG scaffolds. Finally, Mn-MBGNs/gelatin coated scaffolds were shown to be non-cytotoxic to MG-63 cells. Hence, the results presented here confirm that the novel Mn containing scaffolds can be considered in the field of biologically active ion releasing scaffolds for bone tissue engineering applications.
CRIS-Team Scopus Importer:2019-05-14
Keywords: Bioactive glasses; Bone tissue engineering; Gelatin; Manganese; Mesoporous bioactive glass nanoparticles; Scaffolds

Bioactive glass (Bg) icie16 shows promising osteogenic properties compared to crystallized 45s5-bg - Westhauser, Fabian; Hohenbild, Frederike; Arango Ospina, Marcela; Schmitz, Sarah I.; Wilkesmann, Sebastian; Hupa, Leena; Moghaddam, Arash; Boccaccini, Aldo R. (International Journal of Molecular Sciences, 2020)
The ICIE16-bioactive glass (BG) (48.0 SiO2, 6.6 Na2O, 32.9 CaO, 2.5 P2O5, 10.0 K2O (wt %)) has been developed as an alternative to 45S5-BG, the original BG composition (45.0 SiO2, 24.5 Na2O, 24.5 CaO, 6.0 P2O5 (wt %)), with the intention of broadening the BG sintering window while maintaining bioactivity. Because there is a lack of reports on ICIE16-BG biological properties, the influence of ICIE16-BG on viability, proliferation, and osteogenic differentiation of human mesenchymal stromal cells (MSCs) was evaluated in direct comparison to 45S5-BG in this study. The BGs underwent heat treatment similar to that which is required in order to fabricate scaffolds by sintering, which resulted in crystallization of 45S5-BG (45S5-CBG) while ICIE16 remained amorphous. Granules based on both BGs were biocompatible, but ICIE16-BG was less harmful to cell viability, most likely due to a more pronounced pH alkalization in the 45S5-CBG group. ICIE16- BG outperformed 45S5-CBG in terms of osteogenic differentiation at the cellular level, as determined by the increased activity of alkaline phosphatase. However, granules from both BGs were comparable regarding the stimulation of expression levels of genes encoding for osseous extracellular matrix (ECM) proteins. The addition of therapeutically active ions to ICIE16-BG might further improve its ability to stimulate ECM production and should be investigated in upcoming studies.
CRIS-Team Scopus Importer:2020-03-10
Keywords: 45S5 bioactive glass; Human mesenchymal stromal cells; ICIE16 bioactive glass; Osteogenic differentiation; Proliferation

Bioactive glass-biopolymer composites for applications in tissue engineering - Ding, Yaping; Souza, M. T.; Li, Wei; Schubert, Dirk W.; Boccaccini, Aldo R.; Roether, Judith (Springer International Publishing, 2016)
Tissue engineering (TE) is a biomedical field in continuous expansion. However, there are still many challenges to be tackled. The further development of TE approaches requires interdisciplinary interaction and collaboration among various research areas with a notable contribution expected from biomaterials science. In the last couple of decades, significant advances in the development of biomaterial-based scaffolds for hard and soft tissue regeneration have been accomplished, including the manufacture of biocomposites that combine natural or synthetic polymers with bioactive glasses or glass-ceramics. These novel biomaterials present the possibility of tailoring a variety of parameters and properties such as degradation kinetics, mechanical properties, and chemical composition according to the aimed application. This chapter presents a concise update of the field of biopolymer–bioactive glass composite scaffold development for TE covering several popular processing techniques for biocomposite fabrication, namely, microsphere processing, solvent casting-particulate leaching method, electrospinning, freeze-drying, and rapid prototyping techniques, which lead to scaffolds exhibiting a variety of 3D morphologies and different pore structure
Keywords: Degradation; Fabrication techniques; Cell biocompatibility; Composite materials; Soft tissue engineering; Porosity; Scaffolds; Bioactive glass; Bone tissue engineering; Biodegradable polymers

Bioactive glass-biopolymer multilayer coatings fabricated by electrophoretic deposition combined with layer-by-layer assembly - Chen, Qiang; Cabanas Polo, Sandra; Ding, Yaping; Boccaccini, Aldo R. (Key Engineering Materials, 2015)
45S5 bioactive glass (BG) based multilayer coatings on stainless steel were produced by a combination of electrophoretic deposition (EPD) and layer-by-layer (LbL) deposition. The properties of the multilayer coating were tested with different characterization methods including SEM, FTIR, XRD, laser profilometer and water contact angle measurements. Degradation and in-vitro bioactivity behaviors were tested in simulated body fluid (SBF) over different time periods. The decomposition of the coating was inhibited and the hydroxyapatite (HA) formation after short immersion period (0.5d) was confirmed. At the same time, levofloxacin, used as a model antibiotic, was incorporated into the multilayer structure for antibacterial purpose.
Keywords: Bioactive glass; Bioactivity; EPD; Layer-by-layer; Multilayer coating

Bioactive Glass-Ceramic Granules Induce New Bone Formation in a Rat Preclinical Model of Type-1 Diabetes Mellitus - Gomez Gramajo, Fatima; Vargas, Gabriela; Alicia Araoz, Rosa; Vera Mesones, Rosa; Bellido, Teresita; Boccaccini, Aldo R.; Gorustovich, Alejandro (JOURNAL OF BONE AND MINERAL RESEARCH, 2020)
CRIS-Team WoS Importer:2021-01-08

Bioactive Glass-Ceramics - Hoppe, A.; Boccardi, Elena; Ciraldo, Francesca; Boccaccini, Aldo R.; Hill, R. G. (Comprehensive Biomaterials II, 2017)
The processing route and synthesis of glass-ceramics are briefly reviewed including crystal nucleation and crystal growth. This is followed by a review of apatite-based glass-ceramics. The apatite-wollastonite (AW) system is reviewed in terms of its crystallization behavior, physical and mechanical properties, and biological behavior. Subsequently, other types of apatite glass-ceramics are reviewed including apatite-mullite (AM) glass-ceramics, which has good mechanical properties like the AW glass-ceramics and can be cast to shape. Also, advances in bioactive glass-ceramics based on 45S5 Bioglass and other silicate compositions are discussed.
CRIS-Team Scopus Importer:2022-08-05
Keywords: Apatite-mica glass-ceramics; Apatite-mullite glass-ceramics; Apatite-wollastonite (AW) glass-ceramics; Bioactive glass; Bioceramic; Hydroxyapatite; Tetrasilicic mica; Trisilicic mica

Bioactive glass-ceramic scaffolds: Processing and properties - Boccardi, Elena; Ciraldo, Francesca; Boccaccini, Aldo R. (Mrs Bulletin, 2017)
Keywords: biomedical; bone; ceramic; tissue

Bioactive glass coating using aerosol deposition - Eckstein, Udo; Detsch, Rainer; Khansur, Neamul Hayet; Brehl, Martin; Deisinger, Ulrike; de Ligny, Dominique; Boccaccini, Aldo R.; Webber, Kyle Grant (Ceramics International, 2019)
This work demonstrates the successful deposition of bioactive glass (BG)45S5 coatings on various metallic and ceramic substrates at room temperature under low vacuum condition by using aerosol deposition (AD). This room temperature and particle impact consolidation-based deposition method enabled us to deposit well-adhered and dense BG coatings directly on metallic and ceramic substrates. In vitro tests with human osteoblast-like cells on substrates with a 45S5 BG coating demonstrated high cell activity on the surfaces. All tested materials exhibited high in vitro biocompatibility as no inhibition in cell proliferation could be observed. The utilization of AD process for achieving non-crystalline BG coatings is promising for practical bio-medical applications, e.g., bioactive coatings on bioinert metallic and ceramic substrates.
CRIS-Team Scopus Importer:2019-05-17
Keywords: Aerosol deposition; Bioactive coatings; Bioactive glasses; In vitro

Bioactive glass combined with zein as composite material for the application in bone tissue engineering - Hum, Jasmin; Naseri, Shiva; Boccaccini, Aldo R. (Biomedical Glasses, 2018)
Keywords: bone tissue engineering; Bioactive glass; plasticization; composite material; zein; scaffold

Bioactive Glass Containing Coatings by Electrophoretic Deposition: Development and Applications - Heise, Svenja; Ramos Rivera, Laura; Boccaccini, Aldo R. (Biomedical, Therapeutic and Clinical Applications of Bioactive Glasses, 2018)

Bioactive glasses and glass-ceramics versus hydroxyapatite: Comparison of angiogenic potential and biological responsiveness - Bellucci, Devis; Braccini, Simona; Chiellini, Federica; Balasubramanian, Preethi; Boccaccini, Aldo R.; Cannillo, Valeria (Journal of Biomedical Materials Research Part A, 2019)
Different bioactive glasses (BGs), bioceramics, and their composites were extensively analyzed in terms of biological responsiveness and angiogenic potential. In particular several inorganic materials were considered, namely the widely used 45S5 BG, an experimental BG with low tendency to crystallize, other three experimental BGs doped with strontium and/or magnesium, a commercial hydroxyapatite (HA), and two BG–HA composites (with varying percentages of BG and HA). All these materials were ad hoc prepared and in vitro tested by means of an extensive biological analysis, such as MC3T3-E1 cell viability and proliferation by direct contact assay, alkaline phosphatase activity, mineralized matrix deposition analysis by alizarin red staining, as well as evaluation of angiogenic potential and vascular endothelial growth factor release using ST2 cells. Thus, this investigation allows gaining a deeper insight into the biological performance of different inorganic material categories, and to critically compare the different possible solutions, as bone/tissue substitutes for enhanced healing and repair, in terms of bioactivity and regenerative potential.
CRIS-Team Scopus Importer:2019-08-27
Keywords: angiogenesis; bioactive composites; bioactive glasses; bioceramics; in vitro biological tests; magnesium; strontium

BIOACTIVE GLASSES AND THE IMMUNE SYSTEM: RECENT FINDINGS AND FUTURE PERSPECTIVES - Boccaccini, Aldo R.; Schuhladen, Katharina; Steinkasserer, Alexander; Zinser, Elisabeth (TISSUE ENGINEERING PART A, 2022)
CRIS-Team WoS Importer:2022-08-12

Bioactive glasses as angiogenic agents for tissue engineering - Schuhladen, Katharina; Boccaccini, Aldo R. (Encyclopedia of Tissue Engineering and Regenerative Medicine, 2019)
Angiogenesis is controlled by several regulators and is essential for the success of any healing or regenerative process in the human body. By using bioactive glasses (BGs) of varying compositions, angiogenesis and its regulators can be effective stimulated. The angiogenic effect of BGs is mainly the result of the release of biologically active ions during their immersion in the human body. By fine-tuning the compositions of BGs, the release kinetics of ions can be controlled and specific cellular responses and tissue reactions can be achieved. This article discusses BGs of different compositions in their applications in vascularization strategies for tissue engineering.
CRIS-Team Scopus Importer:2020-02-21
Keywords: Angiogenesis; Bioactive glasses; Borate glasses; Ion concentration; Ion doping; Ion release; Mesoporous glasses; Regulators of angiogenesis; Silicate glasses; Therapeutic ions; Tissue engineering; Vascularization; VEGF

Bioactive glasses as carriers for bioactive molecules and therapeutic drugs: a review - Hum, Jasmin; Boccaccini, Aldo R. (Journal of Materials Science: Materials in Medicine, 2012)
Bioactive glasses (BG) show great promise for bone tissue engineering based on their key properties, e.g., biocompatibility, biodegradability, osteoconductivity as well as osteogenic and angiogenic potential, which make them excellent candidates for bone tissue scaffolds and bone substitute materials. Recent work has shown that dissolution products of bioactive glasses have the potential to induce angiogenesis in addition to their known effect of influencing gene expression and promoting osteoblastic differentiation. One of the most interesting features of BG is their ability to bond both to soft and hard tissues, depending on their composition. To intensify the positive impact of BG for medical applications, there are considerable research efforts on using bioactive glass based platforms as carriers for the encapsulation, delivery and controlled release of bioactive molecules and therapeutic drugs. Different types of bioactive glasses have been considered in combination with different therapeutic drugs, hormones, growth factors and peptides. Using bioactive glasses as drug delivery system combines thus the effectiveness of therapeutic drugs (or bioactive/signaling molecules) with the intrinsic advantages of this inorganic biomaterial. Considering research carried out in the last 15 years, this review presents the different chemical compositions and morphologies of bioactive glasses used as carrier for bioactive molecules and therapeutic drugs and discusses the expanding potential of BG with drug delivery capability focusing in the field of bone tissue engineering. © Springer Science+Business Media, LLC 2012.
UnivIS-Import:2015-03-09:Pub.2012.tech.IW.LM.bioact

Bioactive glasses beyond bone and teeth: Emerging applications in contact with soft tissues - Miguez Pacheco, Valentina; Hench, Larry L.; Boccaccini, Aldo R. (Acta Biomaterialia, 2015)
The applications of bioactive glasses (BGs) have to a great extent been related to the replacement, regeneration and repair of hard tissues, such as bone and teeth, and there is an extensive bibliography documenting the role of BGs as bone replacement materials and in bone tissue engineering applications. Interestingly, many of the biochemical reactions arising from the contact of BGs with bodily fluids, in particular the local increase in concentration of various ions at the glass-tissue interface, are also relevant to mechanisms involved in soft tissue regeneration. An increasing number of studies report on the application of BGs in contact with soft tissues, aiming at exploiting the well-known bioactive properties of BGs in soft tissue regeneration and wound healing. This review focuses on research, sometimes involving preliminary in vitro studies but also in vivo evidence, that demonstrates the suitability of BGs in contact with tissues outside the skeletal system, which includes studies investigating vascularization, wound healing and cardiac, lung, nerve, gastrointestinal, urinary tract and laryngeal tissue repair using BGs in various forms of particulates, fibers and nanoparticles with and without polymer components. Potentially active mechanisms of interaction of BGs and soft tissues based on the surface bioreactivity of BGs and on biomechanical stimuli affecting the soft tissue-BG collagenous bonding are discussed based on results in the literature. (C) 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
Keywords: Bioactive glasses; Soft tissue engineering; Vascularisation; Wound healing

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 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)

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

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

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 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)