Development of "Active" Biomaterial Scaffolds for Islet Transplantation

描述(申请人提供)：我们的长期目标是通过开发一种生物相容的、基于细胞的生物人工胰腺来治疗1型糖尿病(T1 DM)。具体地说，这项建议的重点是开发生物活性、微孔支架，为移植的胰岛提供机械支持、空间分布和增强营养输送。目前开发功能性生物人工胰腺的一个重要障碍是胰岛的氧合不良。在这项研究提案中，我们的目标是通过开发并在微孔支架中加入氧气增强材料来实现这一目标。这项建议的具体目的是：1.设计一种高度多孔的支架，能够为胰岛提供机械支持和空间分布，同时允许设备内的血管形成，从而提高体内的植入效率；将氧增强材料和自由基清除剂引入到大孔支架中，作为一种互补的方法，旨在优化胰岛在体内的植入和长期存活。胰岛的氧合程度将通过体外无创氧气监测来确定。胰岛的活性和功能将通过多种测试进行评估，其中包括：活/死染色、四甲基偶氮唑盐比色法、胰岛素分泌比率(ISR)和组织学检查。边缘质量啮齿动物模型将被用来评估生物活性支架在提高同种异体糖尿病大鼠体内植入效率方面的效果。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性，值得立即关注。本研究是推进1型糖尿病现有治疗方法的重要而必要的一步。它将提高目前和未来治疗糖尿病的成功率和有效性。

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.