Evaluation of a functionalized chitosan and alginate multilayer conformal nanocoating toward improving islet survival in syngeneic mouse islet transplantation

Abstract Encapsulation of pancreatic islet transplants with nano‐thin conformal coatings has been reported to maintain islet cell function and minimize immune rejection in type 1 diabetes (T1D) treatment. Our work investigated a novel combination of non‐immunogenic polyelectrolytes, tetrahydropyran triazole phenyl‐alginate (TZ‐AL) and quaternized phosphocholine‐chitosan (PC‐QCH), for layer‐by‐layer self‐assembly onto the surface of mouse islets. Building on previous work validating coating characteristics and biocompatibility using cell‐derived spheroids, we assessed the immunoprotective properties of the polyelectrolyte coating. This was done through in vitro co‐culture of the polyelectrolytes with mouse‐derived splenocytes enriched for antigen‐presenting cells (APCs) and syngeneic transplantation of coated mouse islets into STZ‐induced diabetic mice. Results indicated that the polyelectrolytes may downregulate APC activation and maturation in vitro. In addition, coated islets successfully restored normoglycemia in syngeneic transplants, as demonstrated by blood glucose measurements, intraperitoneal glucose tolerance tests, and graft immunostaining. These results suggest that the polyelectrolyte coating may modulate APC activation and that coated islets exhibit therapeutic efficacy for glycemic control in T1D.