Engineering β Cell Replacement Therapies for Type 1 Diabetes: Biomaterial Advances and Considerations for Macroscale Constructs

While significant progress has been made in treatments for type 1 diabetes (T1D) based on exogenous insulin, transplantation of insulin-producing cells (islets or stem cell-derived beta cells) remains a promising curative strategy. The current paradigm for T1D cell therapy is clinical islet transplantation (CIT)-the infusion of islets into the liver-although this therapeutic modality comes with its own limitations that deteriorate islet health. Biomaterials can be leveraged to actively address the limitations of CIT, including undesired host inflammatory and immune responses, lack of vascularization, hypoxia, and the absence of native islet extracellular matrix cues. Moreover, in efforts toward a clinically translatable T1D cell therapy, much research now focuses on developing biomaterial platforms at the macroscale, at which implanted platforms can be easily retrieved and monitored. In this review, we discuss how biomaterials have recently been harnessed for macroscale T1D beta cell replacement therapies.