title: Hydrogel for Simultaneous Tunable Growth Factor Delivery and Enhanced Viability of Encapsulated Cells in Vitro.
abstract: Poor cell survival in vitro and in vivo is one of the key challenges in tissue engineering. Prosurvival therapeutic proteins, such as insulin-like growth factor-1 (IGF-1), can promote cell viability but require controlled delivery systems due to their short half-lives and rapid clearance. Biocompatible materials are commonly used for drug delivery platforms or to encapsulate cells for increased viability, but few materials have been used for both applications simultaneously. In this work, we present a dual-use platform. A blend of hyaluronan and methylcellulose, known to promote cell survival, was covalently modified with Src homology 3 (SH3)-binding peptides and demonstrated tunable, affinity-based release of the prosurvival fusion protein SH3-IGF-1. The material also significantly increased the viability of retinal pigment epithelium cells under anchorage-independent conditions. This novel platform is applicable to a broad range of cells and protein therapeutics and is a promising drug delivery/cell transplantation strategy to increase the viability of both exogenous and endogenous cells in tissue engineering applications.
authors.affiliation: Department of Chemistry, University of Toronto , 80 St. George Street, Toronto, Ontario M5S 3H6, Canada.|Donnelly Centre, University of Toronto , 160 College Street, Toronto, Ontario M5S 3E1, Canada.
authors.forename: James
authors.initials: J
authors.lastname: Parker
authors.affiliation: Donnelly Centre, University of Toronto , 160 College Street, Toronto, Ontario M5S 3E1, Canada.|Institute of Biomaterials and Biomedical Engineering, University of Toronto , 164 College Street, Toronto, Ontario M5S 3G9, Canada.
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Mitrousis
authors.affiliation: Department of Chemistry, University of Toronto , 80 St. George Street, Toronto, Ontario M5S 3H6, Canada.|Donnelly Centre, University of Toronto , 160 College Street, Toronto, Ontario M5S 3E1, Canada.|Institute of Biomaterials and Biomedical Engineering, University of Toronto , 164 College Street, Toronto, Ontario M5S 3G9, Canada.|Department of Chemical Engineering and Applied Chemistry, University of Toronto , 200 College Street, Toronto, Ontario M5S 3E1, Canada.
authors.forename: Molly S
authors.initials: MS
authors.lastname: Shoichet
mesh_terms: D018929:Cell Culture Techniques; D049109:Cell Proliferation; D002470:Cell Survival; D002478:Cells, Cultured; D003470:Culture Media / Q000737:chemistry; D004847:Epithelial Cells / Q000502:physiology; D000066449:Human Embryonic Stem Cells / Q000502:physiology; D006801:Humans; D020100:Hydrogels / Q000737:chemistry*; D007334:Insulin-Like Growth Factor I / Q000737:chemistry / Q000494:pharmacology*; D055213:Retinal Pigment Epithelium
chemical_list: D003470:Culture Media; D020100:Hydrogels; C583557:IGF1 protein, human; D007334:Insulin-Like Growth Factor I