Oxidized alginate hydrogels with the GHK peptide enhance cord blood mesenchymal stem cell osteogenesis: A paradigm for metabolomics-based evaluation of biomaterial design

Klontzas ME, Reakasame S, Silva R, Morais JCF, Vernardis S, Macfarlane RJ, Heliotis M, Tsiridis E, Panoskaltsis N, Boccaccini AR, Mantalaris A (2019)


Publication Type: Journal article

Publication year: 2019

Journal

Book Volume: 88

Pages Range: 224-240

DOI: 10.1016/j.actbio.2019.02.017

Abstract

Oxidized alginate hydrogels are appealing alternatives to natural alginate due to their favourable biodegradability profiles and capacity to self-crosslink with amine containing molecules facilitating functionalization with extracellular matrix cues, which enable modulation of stem cell fate, achieve highly viable 3-D cultures, and promote cell growth. Stem cell metabolism is at the core of cellular fate (proliferation, differentiation, death) and metabolomics provides global metabolic signatures representative of cellular status, being able to accurately identify the quality of stem cell differentiation. Herein, umbilical cord blood mesenchymal stem cells (UCB MSCs) were encapsulated in novel oxidized alginate hydrogels functionalized with the glycine-histidine-lysine (GHK) peptide and differentiated towards the osteoblastic lineage. The ADA-GHK hydrogels significantly improved osteogenic differentiation compared to gelatin-containing control hydrogels, as demonstrated by gene expression, alkaline phosphatase activity and bone extracellular matrix deposition. Metabolomics revealed the high degree of metabolic heterogeneity in the gelatin-containing control hydrogels, captured the enhanced osteogenic differentiation in the ADA-GHK hydrogels, confirmed the similar metabolism between differentiated cells and primary osteoblasts, and elucidated the metabolic mechanism responsible for the function of GHK. Our results suggest a novel paradigm for metabolomics-guided biomaterial design and robust stem cell bioprocessing.

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APA:

Klontzas, M.E., Reakasame, S., Silva, R., Morais, J.C.F., Vernardis, S., Macfarlane, R.J.,... Mantalaris, A. (2019). Oxidized alginate hydrogels with the GHK peptide enhance cord blood mesenchymal stem cell osteogenesis: A paradigm for metabolomics-based evaluation of biomaterial design. Acta Biomaterialia, 88, 224-240. https://dx.doi.org/10.1016/j.actbio.2019.02.017

MLA:

Klontzas, Michail E., et al. "Oxidized alginate hydrogels with the GHK peptide enhance cord blood mesenchymal stem cell osteogenesis: A paradigm for metabolomics-based evaluation of biomaterial design." Acta Biomaterialia 88 (2019): 224-240.

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