title: Vasculogenic bio-synthetic hydrogel for enhancement of pancreatic islet engraftment and function in type 1 diabetes.
abstract: Type 1 diabetes (T1DM) affects one in every 400 children and adolescents in the US. Due to the limitations of exogenous insulin therapy and whole pancreas transplantation, pancreatic islet transplantation has emerged as a promising therapy for T1DM. However, this therapy is severely limited by donor islet availability and poor islet engraftment and function. We engineered an injectable bio-synthetic, polyethylene glycol-maleimide hydrogel to enhance vascularization and engraftment of transplanted pancreatic islets in a mouse model of T1DM. Controlled presentation of VEGF-A and cell-adhesive peptides within this engineered material significantly improved the vascularization and function of islets delivered to the small bowel mesentery, a metabolically relevant site for insulin release. Diabetic mice receiving islets transplanted in proteolytically degradable hydrogels incorporating VEGF-A exhibited complete reversal of diabetic hyperglycemia with a 40% reduction in the number of islets required. Furthermore, hydrogel-delivered islets significantly improved weight gain, regulation of a glucose challenge, and intra-islet vascularization and engraftment compared to the clinical standard of islet infusion through the hepatic portal vein. This study establishes a simple biomaterial strategy for islet transplantation to promote enhanced islet engraftment and function.
authors.affiliation: Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA.
authors.forename: Edward A
authors.initials: EA
authors.lastname: Phelps
authors.forename: Devon M
authors.initials: DM
authors.lastname: Headen
authors.forename: W Robert
authors.initials: WR
authors.lastname: Taylor
authors.forename: Peter M
authors.initials: PM
authors.lastname: Thulé
authors.forename: Andrés J
authors.initials: AJ
authors.lastname: García
mesh_terms: D000818:Animals; D003922:Diabetes Mellitus, Type 1 / Q000601:surgery*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D020100:Hydrogels / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity; D007515:Islets of Langerhans / Q000098:blood supply / Q000502:physiology* / Q000648:ultrastructure; D016381:Islets of Langerhans Transplantation / Q000379:methods*; D008297:Male; D008301:Maleimides / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity; D051379:Mice; D011092:Polyethylene Glycols / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity; D054457:Tissue Scaffolds / Q000737:chemistry*; D042461:Vascular Endothelial Growth Factor A / Q000008:administration & dosage*
chemical_list: D020100:Hydrogels; D008301:Maleimides; D042461:Vascular Endothelial Growth Factor A; D011092:Polyethylene Glycols
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