title: Encapsulation of porcine pancreatic islets within an immunoprotective capsule comprising methacrylated glycol chitosan and alginate.
abstract: Encapsulation of cells in biocompatible polymer matrices represents a powerful tool for cell-based therapies and therapeutic delivery systems. This technology has successfully been used to deliver pancreatic islets to humans for the treatment of Type 1 diabetes. However, the clinical impact of this technology may be improved by reducing the inflammatory response brought on after implantation of capsules in vivo. Within this study a biocompatible polymeric delivery system combining alginate and photo-crosslinked methacrylated glycol chitosan (MGC) was developed. This approach involved encapsulating cells in calcium-alginate beads, coating with MGC and photo-polymerizing using UVA in the presence of photo-initiator (VA-086), resulting in the formation of capsules ∼600 µm in size. Crosslinking of the MGC outer wall allowed control over capsule swelling and improved the capsules overall properties. Capsule characterization demonstrated the stabilizing influence of polymerization and fluorescence imaging showed that the distribution of glycol chitosan is dependent on molecular weight. Good islet viability and insulin release was demonstrated in vitro over the course of a month, and in vivo transplantation of the capsules demonstrated good biocompatibility, particularly when compared with standard alginate/poly-l-ornithine/alginate capsules.
authors.affiliation: Living Cell Technologies (LCT), Auckland, New Zealand.
authors.forename: Anna Louise
authors.initials: AL
authors.lastname: Hillberg
authors.forename: Matthew
authors.initials: M
authors.lastname: Oudshoorn
authors.forename: Janice B B
authors.initials: JB
authors.lastname: Lam
authors.forename: Kalyani
authors.initials: K
authors.lastname: Kathirgamanathan
mesh_terms: D000464:Alginates / Q000737:chemistry* / Q000302:isolation & purification; D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry*; D002214:Capsules; D002236:Carbohydrate Conformation; D002478:Cells, Cultured; D048271:Chitosan / Q000031:analogs & derivatives* / Q000737:chemistry / Q000276:immunology / Q000302:isolation & purification / Q000528:radiation effects; D004339:Drug Compounding / Q000379:methods*; D005260:Female; D005549:Foreign-Body Reaction / Q000517:prevention & control; D020723:Glucuronic Acid / Q000737:chemistry / Q000276:immunology / Q000302:isolation & purification; D006084:Graft Rejection / Q000517:prevention & control*; D006603:Hexuronic Acids / Q000737:chemistry / Q000276:immunology / Q000302:isolation & purification; D020100:Hydrogels; D057927:Hydrophobic and Hydrophilic Interactions; D007515:Islets of Langerhans / Q000378:metabolism; D016381:Islets of Langerhans Transplantation / Q000379:methods*; D008033:Limulus Test; D008297:Male; D008422:Materials Testing; D008689:Methacrylates / Q000737:chemistry* / Q000302:isolation & purification / Q000528:radiation effects; D051379:Mice; D008863:Microspheres; D015394:Molecular Structure; D010455:Peptides; D010529:Peritoneal Cavity; D010539:Permeability; D058105:Polymerization / Q000528:radiation effects; D034421:Sus scrofa; D013552:Swine; D014183:Transplantation, Heterologous; D014466:Ultraviolet Rays
chemical_list: D000464:Alginates; D001672:Biocompatible Materials; D002214:Capsules; D006603:Hexuronic Acids; D020100:Hydrogels; D008689:Methacrylates; D010455:Peptides; C008973:polyornithine; D020723:Glucuronic Acid; D048271:Chitosan
keywords: cell therapy; diabetes; encapsulated cells; foreign body reactions (response); xenotransplantation