title: Photocrosslinked alginate with hyaluronic acid hydrogels as vehicles for mesenchymal stem cell encapsulation and chondrogenesis.
abstract: Ionic crosslinking of alginate via divalent cations allows for high viability of an encapsulated cell population, and is an effective biomaterial for supporting a spherical chondrocyte morphology. However, such crosslinking chemistry does not allow for injectable and stable hydrogels which are more appropriate for clinical applications. In this study, the addition of methacrylate groups to the alginate polymer chains was utilized so as to allow the free radical polymerization initiated by a photoinitiator during UV light exposure. This approach establishes covalent crosslinks between methacrylate groups instead of the ionic crosslinks formed by the calcium in unmodified alginate. Although this approach has been well described in the literature, there are currently no reports of stem cell differentiation and subsequent chondrocyte gene expression profiles in photocrosslinked alginate. In this study, we demonstrate the utility of photocrosslinked alginate hydrogels containing interpenetrating hyaluronic acid chains to support stem cell chondrogenesis. We report high cell viability and no statistical difference in metabolic activity between mesenchymal stem cells cultured in calcium crosslinked alginate and photocrosslinked alginate for up to 10 days of culture. Furthermore, chondrogenic gene markers are expressed throughout the study, and indicate robust differentiation up to the day 14 time point. At early time points, days 1 and 7, the addition of hyaluronic acid to the photocrosslinked scaffolds upregulates gene markers for both the chondrocyte and the superficial zone chondrocyte phenotype. Taken together, we show that photocrosslinked, injectable alginate shows significant potential as a delivery mechanism for cell-based cartilage repair therapies.
authors.affiliation: Fischell Department of Bioengineering, University of Maryland, College Park, Maryland, USA.
authors.forename: Emily E
authors.initials: EE
authors.lastname: Coates
authors.forename: Corinne N
authors.initials: CN
authors.lastname: Riggin
authors.forename: John P
authors.initials: JP
authors.lastname: Fisher
mesh_terms: D000464:Alginates / Q000737:chemistry*; D000818:Animals; D001854:Bone Marrow Cells / Q000502:physiology; D002454:Cell Differentiation; D002470:Cell Survival; D002478:Cells, Cultured; D019902:Chondrocytes / Q000378:metabolism / Q000502:physiology; D020219:Chondrogenesis / Q000502:physiology*; D003432:Cross-Linking Reagents; D004285:Dogs; D005456:Fluorescent Dyes; D005819:Genetic Markers; D006820:Hyaluronic Acid / Q000737:chemistry*; D020100:Hydrogels; D009682:Magnetic Resonance Spectroscopy; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D014677:Pharmaceutical Vehicles; D060888:Real-Time Polymerase Chain Reaction; D013778:Tetrazolium Salts; D013844:Thiazoles
chemical_list: D000464:Alginates; D003432:Cross-Linking Reagents; D005456:Fluorescent Dyes; D005819:Genetic Markers; D020100:Hydrogels; D014677:Pharmaceutical Vehicles; D013778:Tetrazolium Salts; D013844:Thiazoles; D006820:Hyaluronic Acid; C022616:thiazolyl blue