Executive Summary : | Type-1 diabetes (T1D) is an autoimmune disorder affecting over 8 million people globally, including 78,000 children below 15. It is associated with vascular anomalies and an increased death rate. T1D patients rely on exogenous insulin shots to control their blood glucose, but challenges like insulin resistance and organ damage limit permanent cure. The 'holy grail' of diabetes therapy research is achieving insulin independence for TID patients through transplantation of exogenous donor islet cells or tissues. However, transplantation has disadvantages such as blood-mediated reactions, life-long immunosuppression due to foreign body response (FBR), and scarcity of donors. In the last two decades, researchers have attempted to create immunoprotective biomaterials for islet transplantation, but long-lasting treatments are still not present due to lack of long-term cell survival and host acceptance. The proposal aims to develop an implantable device using natural polymers loaded with xenogeneic islets to provide patients with long restoration of normoglycemia. A 3D-printed implantable hydrogel device with patterned channels will be created and loaded with engineered cells secreting fibroblast growth factor 1 (FGF1) stimulating rapid vasculature formation in vivo. Surface coating the construct with immune modulatory small molecules can inhibit damage to beta cells, restoring host acceptance. Xenogeneic rat islets will be inserted into the hydrogel device and transplanted in a T1D diabetic mouse model, potentially causing long-term diabetic reversal for over one year. This technology could significantly impact the lives of millions of individuals affected by T1D by developing a cell therapy solution. |