Pancreatic islet transplantation (PIT) has been tried with consistent and sustained type 1 diabetes reversal. However, the substantial loss of islet cells during the peritransplant period which limits islet graft survival represents a major problem for practical implementation of PIT. Two significant factors associated with this problem are: 1) loss of natural islet extracellular matrix (ECM) microenvironment during islet isolation and 2) the inherent characteristics of particular surgical implantation site for PIT The goal of this proposalis to develop an innovative strategy to provide an ECM mimicking microenvironment that enhances islet survival, function, and engraftment in the omentum. Our proposed hybrid nanosack will serve as a clinically-applicable innovative strategy, as it will be designed for both reconstructing islet-ECM microenvironment and inducing islet revasculazation in the omentum. The hybrid nanosack will consist of 1) a self-assembled peptide amphiphile (PA) nanomatrix gel capable of encapsulating islets with a nurturing microenvironment and 2) a poly (?-caprolactone) electrospun (ePCL) nanofiber sheet with a craterlike porous structure for infiltration of blood vessels and a mechanically stable structure for surgical manipulation. Outcomes from this proposal will support feasibility of the hybrid nanosack for enhanced islet engraftments in the omuntum through following two Specific Aims.
Specific Aim 1 : To demonstrate enhanced survival and function of islets encapsulated in a self-assembled peptide amphiphile nanomatrix gel in vitro.
Specific Aim 2 : To fabricate a hybrid nanosack for extrahepatic islet transplantation and determine revascularization around the omentum in vivo.
Type 1 diabetes has a significant societal impact through long-term complications including kidney failure, blindness, nerve damage, and cardiovascular problems. The goal of this proposal is to develop an innovative strategy to enhance islet survival, function, and engraftment in the omentum to treat type I diabetes.
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