Introduction: Hepatic islets transplantation procedure to treat type I diabetes often results in limited islets survival presumably due to uneven islet distribution, acute inflammatory response and the corresponding oxidative damage. The objective of this study was to assess whether an antioxidant thermoresponsive hydrogel scaffold would support the viability and function of the transplanted islets at an extrahepatic location.

Materials and Methods: To study the antioxidant protection effect of the PPCN scaffold, Redox-sensitive islets were created by transducing the islets with RoGFP lentivirus. The in vivo study is conducted using the streptozotocin-induced diabetic mice model. Islets from syngeneic donors were transplanted either: a) on the epididymal fat pad with PPCN scaffold or b) into the kidney capsule.

Results: Under the induced hydrogen peroxide oxidation stimulation, PPCN scaffold was able to protect the encapsulated islets, minimize the oxidative damage and maintaining the original morphology for upto 18 hrs. For the in vivo islets transplantation, with 200 islets, euglycemia was restored and maintained the next day following the transplantation. IPGTT results suggested comparable glycaemia control to the kidney capsule. Histology study showed that PPCN scaffold got fully integrated with the surrounding native tissue by day 65 with islets and neovasculature observed at the graft site. Meanwhile, we also showed that euglycemia could be achieved 18 days post transplantation with marginal number of islets isolated from single donor.

Discussion: We demonstrated the ability for PPCN to preserve islets viability and protect them from the potential oxidative damage before and after the transplantation. The observed restoration of euglycemia is superior to what has been reported for other hydrogels when taking into account the number of islets required to achieve euglycemia and the time it took to reach the euglycemic state. These findings confirm that a novel citrate-based thermoresponsive scaffold can serve as a versatile platform for extrahepatic islet transplantation.

CITATION INFORMATION: Zhu Y, Zhang X, Ameer G, Luo X. Antioxidant Thermoresponsive Hydrogel as a Versatile Islets Scaffolds for Treating Type I Diabetes. Am J Transplant. 2017;17 (suppl 3).

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