Rational Engineering of Islet Tolerance via Biomaterial-Mediated Immune Modulation

Type 1 diabetes (T1D) onset is characterized by an autoimmune attack on b islet cells within the pancreas, preventing the insulin secretion required to maintain glucose homeostasis. Targeted modulation of key immunoregulatory cell populations is a promising strategy to restore tolerance to b cells. This strategy can be used to prevent T1D onset or reverse T1D with transplanted islets. To this end, drug delivery systems can be employed to transport immunomodulatory cargo to specific cell populations that inhibit autoreactive T cell -mediated destruction of the b cell mass. The rational engineering of biomaterials into nanoscale and microscale drug carriers can facilitate targeted interactions with immune cells. The physicochemical properties of the biomaterial, the delivered immunomodulatory agent, and the target cell populations are critical variables in the design of these delivery systems. In this review, we discuss recent biomaterialsbased drug delivery approaches to induce islet tolerance and the need to consider both immune and metabolic markers of disease progression.