Intracutaneous Transplantation of Islets within a Biodegradable Temporizing Matrix (BTM) as an Alternative Site for Islet Transplantation

Intra-hepatic islet transplantation for type-1 diabetes is limited by the need for multiple infusions and poor islet viability post-transplantation. The development of alternative transplantation sites is necessary to improve islet survival, and facilitate monitoring and retrieval. We tested a clinically proven Biodegradable Temporizing Matrix (BTM), a polyurethane-based scaffold, to generate a well vascularized intracutaneous ‘neo-dermis’ within the skin for islet transplantation.  In murine models, BTM did not impair syngeneic islet renal-subcapsular transplant viability or function, and facilitated diabetes cure for over 150 days. Further, BTM supported functional neonatal porcine islet transplants into RAG-1-/- mice for 400 days. Hence, BTM is non-toxic for islets. two-photon intravital imaging used to map vessel growth through time identified dense vascular networks, with significant collagen deposition and increases in vessel mass up to 30 days post-BTM implantation. In a pre-clinical porcine skin model, BTM implants created a highly-vascularized intracutaneous site by day 7 post-implantation. When syngeneic neonatal porcine islets were transplanted intracutaneously the islets remained differentiated as insulin producing cells, maintained normal islet architecture, secreted c-peptide, and survived for over 100 days. Here we show that BTM facilitates formation of an islet-supportive intracutaneous ‘neo-dermis’ in a porcine pre-clinical model, as an alternative islet transplant site.