Development of "Active" Biomaterial Scaffolds for Islet Transplantation

描述（由申请人提供）：我们的长期目标是通过开发生物相容的、基于细胞的生物人工胰腺来治疗1型糖尿病（T1 DM）。具体而言，该提案的重点是开发生物活性的微孔支架，以提供机械支持，空间分布和增强移植胰岛的营养输送。目前在开发功能性生物人工胰腺方面的努力的一个重要障碍是胰岛的氧合不良。在这项研究提案中，我们的目标是通过在微孔支架内开发和整合氧增强材料来实现这一目标。本提案的具体目标是：1）设计高度多孔的支架，其能够为胰岛提供机械支撑和空间分布，同时允许装置内血管化，从而改善体内植入物功效;以及2.）将氧增强材料和自由基清除剂引入大孔支架中，作为旨在优化胰岛植入和体内长期胰岛存活的补充方法。胰岛的氧合程度将通过体外无创氧监测来确定。将通过多种试验评估胰岛活力和功能，包括：活/死染色、MTT试验、胰岛素分泌率（ISR）和组织学检查。边缘质量啮齿动物模型将用于评估生物活性支架在同种异体糖尿病大鼠中改善植入物功效的作用。公共卫生相关性：T1 DM的广泛流行，加上疾病及其并发症的严重程度，值得立即关注。这项研究是推进目前治疗1型糖尿病（T1 DM）的治疗方法的重要和必要的一步。它将提高目前和未来糖尿病治疗的成功率和疗效。

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.