| Summary: | Abstract Islet transplantation has shown promise as a curative therapy for type 1 diabetes (T1D). However, the side effects of systemic immunosuppression and limited long‐term viability of engrafted islets, together with the scarcity of donor organs, highlight an urgent need for the development of new, improved, and safer cell‐replacement strategies. Induction of local immunotolerance to prevent allo‐rejection against islets and stem cell derived β cells has the potential to improve graft function and broaden the applicability of cellular therapy while minimizing adverse effects of systemic immunosuppression. In this mini review, recent developments in non‐encapsulation, local immunomodulatory approaches for T1D cell replacement therapies, including islet/β cell modification, immunomodulatory biomaterial platforms, and co‐transplantation of immunomodulatory cells are discussed. Key advantages and remaining challenges in translating such technologies to clinical settings are identified. Although many of the studies discussed are preliminary, the growing interest in the field has led to the exploration of new combinatorial strategies involving cellular engineering, immunotherapy, and novel biomaterials. Such interdisciplinary research will undoubtedly accelerate the development of therapies that can benefit the whole T1D population.
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