title: Synthesis of "click" alginate hydrogel capsules and comparison of their stability, water swelling, and diffusion properties with that of Ca(+2) crosslinked alginate capsules.
abstract: Ionically crosslinked alginate hydrogels have been extensively explored for encapsulation and immunoisolation of living cells/tissues to develop implantable cell therapies, such as islet encapsulation for bioartificial pancreas. Chemical instability of these hydrogels during long-term implantation hinders the development of viable cell therapy. The exchange between divalent crosslinking ions (e.g., Ca(+2) ) with monovalent ions from physiological environment causes alginate hydrogels to degrade, resulting in exposure of the donor tissue to the host's immune system and graft failure. The goal of this study was to improve stability of alginate hydrogels by utilizing covalent "click" crosslinking while preserving other biomedically viable hydrogel properties. Alginate was first functionalized to contain either pendant alkyne or azide functionalities, and subsequently reacted via "click" chemistry to form "click" gel capsules. Alginate functionalization was confirmed by NMR and gel permeation chromatography. When compared with Ca(+2) capsules, "click" capsules exhibited superior stability in ionic media, while showing higher permeability to small size diffusants and similar molecular weight cut-off and water swelling. Physicochemical properties of "click" alginate hydrogels demonstrate their potential utility for therapeutic cell encapsulation and other biomedical applications.
authors.affiliation: Center for Devices and Radiological Health/Office of Science and Engineering Laboratories/FDA, Silver Spring, Maryland, 20993-002.|Department of Chemical and Biomolecular Engineering, University of Maryland, Maryland, 20742-2115.
authors.forename: Joyce C
authors.initials: JC
authors.lastname: Breger
authors.affiliation: Center for Devices and Radiological Health/Office of Science and Engineering Laboratories/FDA, Silver Spring, Maryland, 20993-002.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Fisher
authors.affiliation: Center for Devices and Radiological Health/Office of Science and Engineering Laboratories/FDA, Silver Spring, Maryland, 20993-002.
authors.forename: Raghu
authors.initials: R
authors.lastname: Samy
authors.affiliation: Center for Devices and Radiological Health/Office of Science and Engineering Laboratories/FDA, Silver Spring, Maryland, 20993-002.
authors.forename: Steven
authors.initials: S
authors.lastname: Pollack
authors.affiliation: Department of Chemical and Biomolecular Engineering, University of Maryland, Maryland, 20742-2115.
authors.forename: Nam Sun
authors.initials: NS
authors.lastname: Wang
authors.affiliation: Center for Drug Evaluation and Research/Office of Pharmaceutical Science/Office of Generic Drugs/Division of Chemistry III/FDA, Silver Spring, Maryland, 20993-002.
authors.forename: Irada
authors.initials: I
authors.lastname: Isayeva
mesh_terms: D000464:Alginates / Q000737:chemistry*; D002118:Calcium / Q000737:chemistry*; D057930:Click Chemistry; D020723:Glucuronic Acid / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry; D020100:Hydrogels / Q000737:chemistry*; D019397:Pancreas, Artificial
chemical_list: D000464:Alginates; D006603:Hexuronic Acids; D020100:Hydrogels; D020723:Glucuronic Acid; D002118:Calcium
keywords: EDTA titration; NMR; alginate; bioartificial pancreas; cell encapsulation; diffusion; hydrogels; stability; “click” chemistry