title: Improving alginate-poly-L-ornithine-alginate capsule biocompatibility through genipin crosslinking.
abstract: DIABECELL® capsules comprise an inner core of alginate (Alg) coated with a polycationic polymer, poly-L-ornithine (PLO), designed as a stabilizing agent for strengthening the capsule wall, which is masked by an outer layer of biocompatible Alg. These polymeric microcapsules have demonstrated excellent mechanical properties and a reduction in hypoglycemia after tranplantation in human clinical trials; however, degradation of the outer Alg layer leaves the underlying layers of PLO exposed, which ultimately leads to reduced biocompatibility in vivo. Here we aim to improve capsule biocompatibility and to increase the hydrophilic properties of the capsule surface through chemical crosslinking/modification of the PLO layer using genipin. Fluorescence microscopy established crosslinking was limited to the layers of PLO. In vitro experiments confirmed islet viability and insulin release within chemically modified capsules over the course of a month and in vivo investigations demonstrated improved biocompatibility when comparing standard Alg/PLO/Alg capsules with genipin modified capsules.
authors.affiliation: Living Cell Technologies (LCT), Auckland, New Zealand. awilliams@lctglobal.com
authors.forename: Anna L
authors.initials: AL
authors.lastname: Hillberg
authors.forename: Kalyani
authors.initials: K
authors.lastname: Kathirgamanathan
authors.forename: Janice B B
authors.initials: JB
authors.lastname: Lam
authors.forename: Lee Yong
authors.initials: LY
authors.lastname: Law
authors.forename: Olga
authors.initials: O
authors.lastname: Garkavenko
authors.forename: Robert B
authors.initials: RB
authors.lastname: Elliott
mesh_terms: D000464:Alginates / Q000737:chemistry*; D000818:Animals; D000831:Animals, Newborn; D001672:Biocompatible Materials / Q000737:chemistry*; D002214:Capsules; D020099:Coated Materials, Biocompatible; D003432:Cross-Linking Reagents; D015194:Diffusion Chambers, Culture; D004355:Drug Stability; D020723:Glucuronic Acid / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D039823:Iridoids; D016381:Islets of Langerhans Transplantation / Q000379:methods; D008422:Materials Testing; D051379:Mice; D010455:Peptides / Q000737:chemistry*; D034421:Sus scrofa; D014183:Transplantation, Heterologous
chemical_list: D000464:Alginates; D001672:Biocompatible Materials; D002214:Capsules; D020099:Coated Materials, Biocompatible; D003432:Cross-Linking Reagents; D006603:Hexuronic Acids; D039823:Iridoids; D010455:Peptides; C008973:polyornithine; D020723:Glucuronic Acid; C007834:genipin