Development of implantable vascularized pancreatic construct by 3D cell printing technology

Abstract

The transplantation of pancreatic islets is promising treatment for patients of type 1 diabetes, suffering hypoglycaemia and secondary complications. The primary goal of this treatment is to supply sufficient amount of insulin in the bloodstream, however, several limitations still remain. Large number of the islet graft in the intrahepatic transplant site is difficult to survive due to low engraftment rate and hostile environment. In case of subcutaneous transplantation, the viability and function of the implanted islet is diminished because of the low vascularity occurring hypoxic condition. With the convergence of 3D bioprinting, bioink and stem cell biology approaches, tissue engineering offers a promising alternative. Pancreatic islets were encapsulated in Pancreas tissue-derived extracellular matrix (pdECM) bioink in order to provide a physiologically relevant microenvironment, which could improve the viability and functionality of the cells. Also, insulin producing cells(IPCs) were differentiated from human pluripotent stem cells. Human umbilical vein endothelial cells (HUVECs) were co-cultured with the cells in the pancreatic construct in order to prevent hypoxia and provide a positive effect on the islets. We developed the 3D cell printed pancreatic construct using pdECM bioink, IPC and vascular cells that could potential be an advanced islet delivery method for the treatment of type 1 diabetes.