The goal of the Islet Group is to engineer a synthetic poly(ethylene glycol) (PEG) hydrogel system, modified with critical extracellular matrix molecules that support long-term islet survival and function and suppress cell damage from stresses of the immune system. Towards this goal, we are synthesizing gel niches that introduce both cell-cell and cell-matrix interactions and then monitoring functions critical to the overall success of islet transplantation therapies. We are identifying ‘permissive’ hydrogel chemistries, defined as ones that support islet survival and function over the course of 1 monthin vitroand testing the ability of these permissive formulations to support islet function under physiological stress. We also exploit microfabrication technology to create highly defined cell aggregates to better understand the role of islet size on survival and function. Finally, with this understanding, these gel formulations are further modified with immune modulatory antibodies, immunosuppressive proteins and anti-inflammatory anti-oxidative enzymes to establish new strategies to actively promote islet function and long-term survival by locally suppressing the effects of the cells of the host immune and inflammatory responses. The effectiveness of these bioactive cell carriers are then tested in a diabetic animal model in collaborations with Professor Katie Haskins group in Immunology at the National Jewish Health in Denver.