Biomaterials, Biodegradables and Biomimetics Research Group

Papers in Scientific Journals

Hydrogel depots for local co-delivery of osteoinductive peptides and mesenchymal stem cells

Abstract

The outcome of cell-based therapies can benefit from carefully designed cell carriers. A multifunctional injectable vehicle for the co-delivery of human mesenchymal stem cells (hMSCs) and osteoinductive peptides is proposed, to specifically direct hMSCs osteogenic differentiation. The osteogenic growth peptide (OGP) inspired the design of two peptides, where the bioactive portion of OGP was flanked by a protease-sensitive linker, or its scrambled sequence, to provide faster and slower release rates, respectively. Peptides were fully characterized and chemically grafted to alginate. Both OGP analogs released bioactive fragments in vitro, at different kinetics, which stimulated hMSCs proliferation and osteogenesis. hMSCs-laden OGP–alginate hydrogels were tested at an ectopic site in a xenograft mouse model. After 4 weeks, OGP–alginate hydrogels were more degraded and colonized by vascularized connective tissue than the control (without OGP). hMSCs were able to proliferate, migrate outward the hydrogels, produce endogenous extracellular matrix and mineralize it. Moreover, OGP-groups stimulated hMSCs osteogenesis, as compared with the control. Overall, the ability of the proposed platform to direct the fate of transplanted hMSCs in loco was demonstrated, and OGP-releasing hydrogels emerged as a potentially useful system to promote bone regeneration.

Journal
Journal of controlled release
Volume
189
Pagination
158-168
URL
http://www.sciencedirect.com/science/article/pii/S0168365914004295
Keywords
bone regeneration, Co-delivery systems, Guided differentiation, Injectable alginate hydrogels, mesenchymal stem cells, Osteoinductive peptides
Rights
Open Access
Peer Reviewed
Yes
Status
published
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