title: Evaluation of a collagen-chitosan hydrogel for potential use as a pro-angiogenic site for islet transplantation.
abstract: Islet transplantation to treat type 1 diabetes (T1D) has shown varied long-term success, due in part to insufficient blood supply to maintain the islets. In the current study, collagen and collagen:chitosan (10:1) hydrogels, +/- circulating angiogenic cells (CACs), were compared for their ability to produce a pro-angiogenic environment in a streptozotocin-induced mouse model of T1D. Initial characterization showed that collagen-chitosan gels were mechanically stronger than the collagen gels (0.7 kPa vs. 0.4 kPa elastic modulus, respectively), had more cross-links (9.2 vs. 7.4/µm(2)), and were degraded more slowly by collagenase. After gelation with CACs, live/dead staining showed greater CAC viability in the collagen-chitosan gels after 18 h compared to collagen (79% vs. 69%). In vivo, collagen-chitosan gels, subcutaneously implanted for up to 6 weeks in a T1D mouse, showed increased levels of pro-angiogenic cytokines over time. By 6 weeks, anti-islet cytokine levels were decreased in all matrix formulations ± CACs. The 6-week implants demonstrated increased expression of VCAM-1 in collagen-chitosan implants. Despite this, infiltrating vWF(+) and CXCR4(+) angiogenic cell numbers were not different between the implant types, which may be due to a delayed and reduced cytokine response in a T1D versus non-diabetic setting. The mechanical, degradation and cytokine data all suggest that the collagen-chitosan gel may be a suitable candidate for use as a pro-angiogenic ectopic islet transplant site.
authors.affiliation: University of Ottawa Heart Institute, Ottawa, Canada ; Department of Cellular & Molecular Medicine, University of Ottawa, Ottawa, Canada.
authors.forename: Joanne E
authors.initials: JE
authors.lastname: McBane
authors.forename: Branka
authors.initials: B
authors.lastname: Vulesevic
authors.forename: Donna T
authors.initials: DT
authors.lastname: Padavan
authors.forename: Kimberly A
authors.initials: KA
authors.lastname: McEwan
authors.forename: Gregory S
authors.initials: GS
authors.lastname: Korbutt
authors.forename: Erik J
authors.initials: EJ
authors.lastname: Suuronen
mesh_terms: D042501:Angiogenic Proteins / Q000378:metabolism*; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D048271:Chitosan / Q000494:pharmacology*; D003094:Collagen / Q000494:pharmacology*; D016207:Cytokines / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism; D006801:Humans; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000494:pharmacology*; D016381:Islets of Langerhans Transplantation / Q000379:methods; D008297:Male; D051379:Mice; D051381:Rats
chemical_list: D042501:Angiogenic Proteins; D016207:Cytokines; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D003094:Collagen; D048271:Chitosan