title: Oxidized alginate hydrogels as niche environments for corneal epithelial cells.
abstract: Chemical and biochemical modification of hydrogels is one strategy to create physiological constructs that maintain cell function. The aim of this study was to apply oxidised alginate hydrogels as a basis for development of a biomimetic niche for limbal epithelial stem cells that may be applied to treating corneal dysfunction. The stem phenotype of bovine limbal epithelial cells (LEC) and the viability of corneal epithelial cells (CEC) were examined in oxidised alginate gels containing collagen IV over a 3-day culture period. Oxidation increased cell viability (P ≤ 0.05) and this improved further with addition of collagen IV (P ≤ 0.01). Oxidised gels presented larger internal pores (diameter: 0.2-0.8 µm) than unmodified gels (pore diameter: 0.05-0.1 µm) and were significantly less stiff (P ≤ 0.001), indicating that an increase in pore size and a decrease in stiffness contributed to improved cell viability. The diffusion of collagen IV from oxidised alginate gels was similar to that of unmodified gels suggesting that oxidation may not affect the retention of extracellular matrix proteins in alginate gels. These data demonstrate that oxidised alginate gels containing corneal extracellular matrix proteins can influence corneal epithelial cell function in a manner that may impact beneficially on corneal wound healing therapy.
authors.affiliation: School of Chemistry, Food and Pharmacy, Department of Pharmaceutics, University of Reading, Reading, Berkshire, RG6 6UB, United Kingdom.
authors.forename: Bernice
authors.initials: B
authors.lastname: Wright
authors.forename: Paul A
authors.initials: PA
authors.lastname: De Bank
authors.forename: Kim A
authors.initials: KA
authors.lastname: Luetchford
authors.forename: Fernando R
authors.initials: FR
authors.lastname: Acosta
authors.forename: Che J
authors.initials: CJ
authors.lastname: Connon
mesh_terms: D000464:Alginates / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D002417:Cattle; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D060833:Cellular Microenvironment / Q000187:drug effects*; D024141:Collagen Type IV / Q000378:metabolism; D004058:Diffusion; D004847:Epithelial Cells / Q000166:cytology*; D019573:Epithelium, Corneal / Q000166:cytology*; D020723:Glucuronic Acid / Q000737:chemistry / Q000494:pharmacology; D006603:Hexuronic Acids / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D020100:Hydrogels / Q000494:pharmacology*; D016850:Limbus Corneae / Q000166:cytology*; D010084:Oxidation-Reduction; D010641:Phenotype; D016062:Porosity; D014867:Water / Q000737:chemistry
chemical_list: D000464:Alginates; D024141:Collagen Type IV; D006603:Hexuronic Acids; D020100:Hydrogels; D014867:Water; D020723:Glucuronic Acid
keywords: alginate gel porosity; alginate gel stiffness; limbal epithelial cells; limbal stem cell deficiency; oxidised alginate