Pancreatic tissue engineering faces vascularization hurdle in type 1 diabetes therapy

Type 1 diabetes results from autoimmune destruction of pancreatic β-cells, and while whole-organ pancreas and islet transplantation can restore endogenous insulin secretion, both are limited by donor scarcity, early inflammatory injury, hypoxia, and the need for lifelong immunosuppression. Pancreatic tissue engineering has therefore emerged as a strategy to generate scalable, transplantable constructs capable of reestablishing physiological glucose regulation. However, as native islets depend on a robust microvascular network for oxygen delivery, nutrients and coordinated hormone secretion, insufficient vascularization remains the dominant cause of engineered graft failure. This review provides an overview of (a) the current state of pancreas transplant, (b) strategies for vascularized and immunoprotective pancreatic constructs, (c) cell differentiation strategies beyond of pancreatic β-cells, (d) translational progress in animal and human clinical trials, (e) key challenges in clinical translation, (f) ethical and regulatory considerations, and (g) future directions for tissue engineered pancreatic constructs. Our goal is to provide the reader with a translational overview that spans biology, tissue engineering, and clinical translation. This translational review provides a concise review of tissue engineering efforts to date within the context of engineered pancreatic constructs. Our paper systematically and logically discusses current developments, challenges, and novel approaches in pancreatic tissue engineering. It provides a digestible starting point for understanding the various approaches and the implications of successful tissue engineering strategies that can be used to develop transplantable pancreatic constructs.