Type 1 diabetes mellitus (T1DM) is an autoimmune condition that results in the destruction of insulin-secreting β cells of the islets of Langerhans. Allogeneic islet transplantation could be a successful treatment for T1DM; however, it is limited by the need for effective, permanent immunosuppression to prevent graft rejection. Upon transplantation, islets are rejected through non-specific, alloantigen specific, and recurring autoimmune pathways. Immunosuppressive agents used for islet transplantation are generally successful in inhibiting alloantigen rejection, but they are suboptimal in hindering non-specific and autoimmune pathways. In this review, we summarize the challenges with cellular immunological rejection and therapeutics used for islet transplantation. We highlight agents that target these three immune rejection pathways and how to package them for controlled, local delivery via biomaterials. Exploring macro-, micro-, and nano-scale immunomodulatory biomaterial platforms, we summarize their advantages, challenges, and future directions. We hypothesize that understanding their key features will help identify effective platforms to prevent islet graft rejection. Outcomes can further be translated to other cellular therapies beyond T1DM.

1 型糖尿病(T1DM) 是一种自身免疫性疾病，会导致胰岛分泌胰岛素的 β 细胞遭到破坏。同种异体胰岛移植可能是 T1DM 的成功治疗方法；然而，由于需要有效、永久的免疫抑制来防止移植物排斥，它受到限制。移植后，胰岛通过非特异性、同种异体抗原特异性和反复出现的自身免疫途径被排斥。用于胰岛移植的免疫抑制剂通常能成功抑制同种抗原排斥，但在阻碍非特异性和自身免疫途径方面效果不佳。在这篇综述中，我们总结了细胞免疫排斥和胰岛移植治疗所面临的挑战。我们重点介绍针对这三种免疫排斥途径的药物，以及如何将它们包装起来，通过生物材料进行受控的局部递送。通过探索宏观、微观和纳米级免疫调节生物材料平台，我们总结了它们的优势、挑战和未来方向。我们假设了解它们的主要特征将有助于确定预防胰岛移植排斥的有效平台。结果可以进一步转化为 T1DM 以外的其他细胞疗法。