Engineering early immune resilience in islet transplantation

Pancreatic islet transplantation holds the promise of restoring natural insulin control in type 1 diabetes, yet most transplanted islets are destroyed within hours by the instant blood-mediated inflammatory reaction (IBMIR), a thrombo-inflammatory burst that has long limited clinical success. This early barrier matters because it prevents durable graft function even when immunosuppression is optimal. Recent advances in pharmacological and cell-intrinsic interventions, biomaterial-based modulation, and the strategic use of extrahepatic transplant sites have begun to transform our ability to modulate this reaction. This review integrates these developments to reposition IBMIR as a targetable and mechanistically understood process. We provide a forward-looking synthesis that outlines how converging technologies can build an immune-resilient microenvironment for durable, scalable islet transplantation.