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Pancreatic Extracellular Matrix and Platelet-rich Plasma Constructing Injectable Hydrogel For Pancreas Tissue Engineering.

The development of pancreatic extracellular matrices enriched with insulin-secreting β cells is a promising tissue engineering approach to treat type-1 diabetes. However, its long-term therapeutic efficacy is restricted by the defensive mechanism of host immune response and the lack of developed vascularization as appropriate after transplantation. Platelet-rich plasma (PRP), as an autologous platelet concentrate, contains a large number of active factors that are essential for the cell viability, vascularization, and immune regulation. In this study, we have incorporated pancreatic extracellular matrix (PEM) with PRP to develop a three-dimensional (3D) injectable PEM-PRP hydrogel to co-culture and transplant rat insulinoma cells (INS-1) and human umbilical vein endothelial cells (HUVEC). Results from this study demonstrated that PEM-PRP hydrogel mimicked the biochemical compositions of native extracellular matrices, and possessed the enhanced elastic modulus and resistance to enzymatic degradation that enabled biomaterials to maintain its volume and slowly degrade. Additionally, PEM-PRP hydrogel could release growth factors in a sustained manner. In vitro, PEM-PRP hydrogel significantly promoted the viability, insulin-secreting function and insulin gene expression of gel encapsulated INS-1 cells. Moreover, HUVECs encapsulated in PEM-PRP hydrogel was found to constitute many lumen-like structure and exhibited high expression of proangiogenic genes. In vivo transplantation of PEM-PRP hydrogel encapsulated with INS-1 cells and HUVECs improved the viability of INS-1 cells, promoted vascularization, inhibited the host inflammatory response, and reversed hyperglycemia of diabetic rats. Our study suggests that the PEM-PRP hydrogel offers excellent biocompatibility and proangiogenic property, and may serve as an effective biomaterial platform to maintain the long-term survival and function of insulin-secreting β cells.