A stepwise funnel selection approach identifying natural polymer-derived hydrogels for long-term islet delivery, restoring normoglycemia in type-1 diabetes

Abstract

Transplantation of encapsulated islet cells can restore the normal physiological glycemic level in type-1 diabetic patients. However, the clinical rate of success of islet transplantation is limited by robust immune response, inadequate insulin release, and acute hypoxic stress. The physico-biochemical properties of an encapsulating hydrogel play an important role in successful islet transplantation, mitigating the challenges. Herein, we report a comprehensive screening of 20 different commonly available natural polymers based on their various physico-biochemical properties, ease of islet delivery (MIN6), and biological functioning. From the initial screening, the top four leads (alginate, pectin, agarose, and cellulose) were selected based on their long-term degradation, mechanical stability, and insulin release kinetics. Based on further in vitro assessment, pectin was identified as the lead polymer for the in vivo diabetes treatment study. Subcutaneous implantation of MIN6 (mouse beta pancreatic islet) encapsulated pectin hydrogel capsules restored and maintained normoglycemia for 60 days in both C57BL/6 (allogeneic) mice and Wistar rats (xenogeneic) in a streptozotocin-induced diabetic model, without the requirement of any external immunosuppressant. Furthermore, when pectin was used for encapsulation and delivery of isolated primary rat islets to diabetic C57BL/6 mice, it also restored normoglycemia within 3 days of transplantation in the xenogeneic setup and sustained it for 30 days. This study successfully identified a novel natural polymer, pectin, demonstrating potential for maintaining long-term islet viability in vivo and acting as an independent, promising platform for islet delivery in the management of type-1 diabetes.