title: 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 4weeks, 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.
authors: INEB-Instituto de Engenharia Biomédica, Rua do Campo Alegre, n.° 823, 4150-180 Porto, Portugal; FEUP-Faculdade de Engenharia Universidade do Porto, Rua Dr. Roberto Frias s/n, 4200-465 Porto, Portugal.
authors: F Raquel
authors: FR
authors: Maia
authors: INEB-Instituto de Engenharia Biomédica, Rua do Campo Alegre, n.° 823, 4150-180 Porto, Portugal.
authors: Mariana
authors: M
authors: Barbosa
authors: INEB-Instituto de Engenharia Biomédica, Rua do Campo Alegre, n.° 823, 4150-180 Porto, Portugal; FEUP-Faculdade de Engenharia Universidade do Porto, Rua Dr. Roberto Frias s/n, 4200-465 Porto, Portugal.
authors: David B
authors: DB
authors: Gomes
authors: CIQ-UP, Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade do Porto, Rua do Campo Alegre 687, 4169-007 Porto, Portugal.
authors: Nuno
authors: N
authors: Vale
authors: CIQ-UP, Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade do Porto, Rua do Campo Alegre 687, 4169-007 Porto, Portugal.
authors: Paula
authors: P
authors: Gomes
authors: INEB-Instituto de Engenharia Biomédica, Rua do Campo Alegre, n.° 823, 4150-180 Porto, Portugal; FEUP-Faculdade de Engenharia Universidade do Porto, Rua Dr. Roberto Frias s/n, 4200-465 Porto, Portugal; ICBAS-Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Rua de Jorge Viterbo Ferreira n.° 228, 4050-313 Porto, Portugal.
authors: Pedro L
authors: PL
authors: Granja
authors: INEB-Instituto de Engenharia Biomédica, Rua do Campo Alegre, n.° 823, 4150-180 Porto, Portugal. Electronic address: ccbarrias@ineb.up.pt.
authors: Cristina C
authors: CC
authors: Barrias
mesh_terms: D000464:Alginates / Q000737:chemistry; D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D016503:Drug Delivery Systems; D020723:Glucuronic Acid / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry; D006657:Histones / Q000008:administration & dosage* / Q000737:chemistry; D006801:Humans; D020100:Hydrogels / Q000008:administration & dosage* / Q000737:chemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000008:administration & dosage* / Q000737:chemistry; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000166:cytology; D016513:Mice, SCID; D010012:Osteogenesis
chemical_list: D000464:Alginates; D006603:Hexuronic Acids; D006657:Histones; D020100:Hydrogels; D036341:Intercellular Signaling Peptides and Proteins; C074533:osteogenic growth peptide; D020723:Glucuronic Acid
keywords: Bone regeneration; Co-delivery systems; Guided differentiation; Injectable alginate hydrogels; Mesenchymal stem cells; Osteoinductive peptides