Type 1 Diabetes (T1D) leads to autoimmune destruction of pancreatic islet β cells, the body's sole source of insulin, resulting in potentially life-threatening impairment of glucose and metabolic regulation. The current standard of care involves daily measures of blood glucose, and injection of exogenous insulin. Recent advances suggest that transplanted replacement islets could functionally 'cure' T1D, but these strategies require chronic immunosuppression to prevent destruction of the transplanted allogeneic cells. Additionally, islet cells are currently sourced from cadaveric donors, resulting in highly variable islet supply and quality. In this Bio-X proposal, we propose to develop an implantable cell-device combination technology that concentrates reaggregated human islet cells in an immunoprotective bioelectronic device. The reaggregated islets, known as pseudo-islets (p-islets) and developed by Prof. Seung K. Kim’s group, have enhanced size uniformity and potency in regulated insulin output compared to native pancreatic islets, thereby addressing quality and variability challenges. The bioelectronic encapsulation devices, developed by Prof. Siddharth Krishnan’s lab, provide essential 'life support' to islet cells through immune-protection, oxygenation and 3D organization, and ensure access to nutrients in the bloodstream. Together, combination of human p-islets and bioelectronic studies to provide islet replacement without systemic immunosuppression would be a transformative breakthrough for diabetes care.