![]() ![]() Up to 2/3 of transplanted islets die in the first few days post-transplant, and while the remaining islets are sufficient to achieve initial diabetes reversal, hyperglycemia eventually returns as islets are lost. This islet mass represents nearly tenfold more than theoretically needed to maintain normoglycemia. To achieve diabetes reversal, patients generally receive islets from 2 to 4 donors via hepatic portal infusion. Although current protocols achieve an initial diabetes reversal of over 90%, this rate drops as low as 30% and 10% by 2 and 5 years post-transplantation. Islet transplantation is a promising treatment to ameliorate diabetes and eliminate the need for exogenous insulin therapy. Despite advances in insulin types and delivery mechanisms, hypoglycemic events and micro/macro-vascular complications persist. Type 1 diabetes mellitus (T1DM) is a life-long endocrine disorder managed by chronic insulin therapy. ![]() These results demonstrate scaffolds support murine islet transplantation with high efficiency, and feasibility studies in large animals support continued pre-clinical studies with scaffolds as a platform to control the transplant microenvironment. Transplantation into the porcine omentum provided greater islet engraftment than the gastric submucosa. Increasing the islet seeding density led to a greater mass of engrafted islets, though the efficiency of islet survival decreased. The porcine model was used to investigate early islet engraftment. Increasing the pore size to increase islet-islet interactions did not significantly impact islet function. In the diabetic mouse model, 125 islets seeded on scaffolds implanted into the epididymal fat pad restored normoglycemia within an average of 1.95 days and transplantation of only 75 islets required 12.1 days. Scaffold architecture was modified to enhance cell infiltration leading to re-vascularization of the islets with minimal inflammatory response. We investigated non-encapsulating, porous, biodegradable polymer scaffolds as a vehicle for islet transplantation into extrahepatic sites, using syngeneic mouse and allogeneic porcine models. However, intravascular infusion and the intrahepatic site contribute to significant early and late islet loss, yet a clinical alternative has remained elusive. Intraportal transplantation of islets has successfully treated select patients with type 1 diabetes. ![]()
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