Hydrogel injection molded complex macroencapsulation device geometry improves long-term cell therapy viability and function in the rat omentum transplant site

Abstract

Insulin-secreting allogeneic cell therapies are a promising treatment for type 1 diabetes, with the potential to eliminate hypoglycemia and long-term complications of the disease. However, chronic systemic immunosuppression is necessary to prevent graft rejection, and the acute risks associated with immunosuppression limit the number of patients who can be treated with allogeneic cell therapies. Islet macroencapsulation in a hydrogel biomaterial is one proposed method to reduce or eliminate immune suppression; however, macroencapsulation devices suffer from poor oxygen transport and limited efficacy as they scale to large animal model preclinical studies and clinical trials. Hydrogel geometric device designs that optimize nutrient transport combined with methods to promote localized vasculogenesis may improve in vivo macroencapsulated cell viability and function. Here, we demonstrate with finite element modeling that a high surface area-to-volume ratio spiral geometry can increase macroencapsulated islet viability and function relative to a traditional cylindrical design, and we validate these observations in vitro under normoxic and physiological oxygen conditions. Finally, we evaluate macroencapsulated syngeneic islet survival and function in vivo in a diabetic rat omentum transplant model, and demonstrate that high surface area-to-volume hydrogel device designs improved macroencapsulated syngeneic islet function relative to traditional device designs.