Vascularization is one of the biggest challenges in tissue engineering. For people with type 1 diabetes, re-vascularization is essential for the long-term survival and function of transplanted pancreatic islet cells. After transplantation, more than 90% of the islets can be lost, mainly because they do not get enough nutrients and oxygen. As a result, pancreatic islets without blood vessels often die after transplantation, which limits how well islet replacement therapies work. We believe that adding blood vessels to supply nutrients will improve islet survival and function. To achieve this, we are creating blood vessel cells from human pluripotent stem cells, including endothelial cells, smooth muscle cells, and fibroblasts, to build 3D blood vessels. We will combine these with pancreatic islets to produce 'pre-vascularized' islets, which could help develop new cell replacement treatments for diabetes. Our project focuses on two main challenges. First, while engineered microvessels can form hollow tubes in the lab, these tubes often become narrow, collapse, or leak over time. To overcome this, we will test whether natural blood flow helps keep vessels stable and functional (Aim 1). Second, although some tissue interactions that support vascularization are known, they have not yet been found in islets. To fill this gap, we will study whether signals from nearby islets help blood vessels grow and connect (Aim 2).