Development of "Active" Biomaterial Scaffolds for Islet Transplantation

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DESCRIPTION (provided by applicant): Our long-term objective is to treat type 1diabetes mellitus (T1DM) by developing a biocompatible, cell-based, bioartificial pancreas. Specifically, this proposal is focused on the development of bioactive, microporous scaffolds to provide mechanical support, spatial distribution, and enhanced nutrient delivery to transplanted islets. A significant hindrance for current efforts in the development of a functional bioartificial pancreas is poor oxygenation of pancreatic islets. In this research proposal, we aim to advance towards that goal by developing and incorporating oxygen enhancing materials within a microporous scaffold. The specific aims of this proposal are to: 1.) Design a highly porous scaffold capable of providing mechanical support and spatial distribution to the islets, while permitting intra-device vascularization, thereby improving implant efficacy in vivo; and 2.) Introduce oxygen enhancing materials and free-radical scavengers into the macroporous scaffold as a complementary approach designed to optimize islet engraftment and long-term islet survival in vivo. The degree of oxygenation of islets will be determined by non-invasive oxygen monitoring in vitro. Islet viability and functionality will be assessed by a multitude of tests that include: Live/Dead staining, MTT assay, insulin secretion ratio (ISR), and histological examination. Marginal mass rodent models will be used to assess the effects of bioactive scaffolds in improving implant efficacy within allogeneic diabetic rats. PUBLIC HEALTH RELEVANCE: The widespread prevalence of T1 DM, coupled with the severity of the disease and its complications, warrants immediate attention. This research is a significant and necessary step to advancing current therapeutic methods for treating Type 1 diabetes mellitus (T1DM). It will improve the success and efficacy of current and future therapeutic diabetes treatment.