Injectable self-healing hydrogels loaded with islet-integrated microfiber scaffolds for islet transplantation in diabetes mellitus

Current research on islet transplantation is aimed at prolonging the survival time and enhancing the functionality of the transplantation system. Owing to the good biocompatibility of hydrogels and their ability to provide mechanical support and immunological isolation of islet cells, hydrogel encapsulation of islets offers an innovative solution for islet transplantation. In this work, inspired by the extracellular matrix structure of the pancreatic islets, an injectable self-healing hydrogel loaded with islet-integrated microfiber scaffolds was constructed for islet transplantation. The short microfiber was fabricated by introducing a gaseous phase into microfluidic spinning, causing the continuous microfibers to break into short segments due to bubble rupture. These short microfibers provide mechanical support for pancreatic islets and can be integrated into a self-healing matrix to form a vascularized hydrogel through Schiff base bonding of oxidized sodium alginate aldehyde groups with carboxymethyl chitosan amino groups. With the loading of human umbilical vein endothelial cells and vascular endothelial growth factor, this composite is both injectable and provides mechanical support for the grafts, extends islet survival time, and improves islet function. In vivo experiments further confirm that this bioinspired composite system minimizes implantation-associated trauma while promoting neovascularization at the graft site in diabetic rodents, thereby achieving prolonged glycemic control compared to non-vascularized systems. These findings demonstrate that this hierarchically structured multifunctional graft platform has substantial research value and extensive therapeutic potential in the fields of cell therapy and tissue engineering for the treatment of diabetes and related diseases.