Functionalized, Nanoscale Coatings for Islet Encapsulation

用于胰岛封装的功能化纳米级涂层

• 批准号: 8139436
• 负责人: Cherie L Stabler
• 金额: $ 0.23万
• 依托单位: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-30 至 2013-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8139436
• 关键词: Anti-Inflammatory Agents; Antigens; Biocompatible Materials; Cell surface; Clinical; Encapsulated; Engraftment; Environment; Enzymes; Failure; Grant; Immune response; Implant; Individual; Inflammatory; Insulin-Dependent Diabetes Mellitus; Islets of Langerhans Transplantation; Lead; Link; Nutritional; Polymers; Proteins; Public Health; Research; Structure; Surface; Therapeutic immunosuppression; Thick; Transplantation; capsule; design; glucose transport; implantation; improved; islet; loss of function; nano; nanometer; nanoparticle; nanoscale; novel; response

Grant: RFA- DK-08-001 Title: Functionalized, Nanoscale Coatings for Islet Encapsulation PI: Cherie Stabler Project Summary While clinical islet transplantation (CIT) has shown promise for the treatment of Type 1 diabetes, it is dampened by the impaired function and loss of islets following implantation. This loss is attributed to strong inflammatory and immunological response to the transplant, primarily due to cell surface inflammatory proteins and antigens. In this proposal, we seek to minimize detrimental host responses that lead to islet engraftment failure by encapsulating the islets in novel nanoscale biomaterial layers. By developing stable capsules on the order of 1000-fold smaller than standard practices via controlled covalent linking of individual polymers layers on the islet surface, void volumes are dramatically reduced and nutritional transport and glucose sensing is unaffected. Nanoscale layers not only serve as a means to immunocamouflage the implant, but also have tremendous potential to optimize the composition, structure, thickness, and function of these layers on the nanometer level. Once fabricated, these nanoscale layers serve as ideal platforms for the tethering of functional agents, proteins or markers capable of dynamically interacting at the implant-host interface. Therefore, the inert biomaterial layer can be converted to a bioactive surface capable of actively altering the localized implant environment. In this proposal, we seek to tether active immunomodulatory proteins/enzymes, anti-inflammatory agents, and/or engraftment- enhancing nanoparticles to the nanolayer surface. The design of effective strategies to build tailored nano-layers on the islet surface capable of expressing active pro- engraftment agents could significantly improve transplant efficacy and long-term stability. The public health implications of this research are that this approach may provide a means to dramatically improve current clinical islet transplantation results, by reducing or completely eliminating the need for immunosuppressive therapy and improving long- term implant function.

赠款：RFA-DK-08-001 标题：胰岛封装功能化的纳米级涂料 PI：Cherie Stabler 项目摘要 虽然临床胰岛移植（CIT）显示出对1型治疗的有望 糖尿病，它因功能受损和胰岛损失而抑制 植入。这种损失归因于强烈的炎症和免疫反应 移植，主要是由于细胞表面炎症蛋白和抗原。在这个 提案，我们试图最大程度地减少导致胰岛植入的有害宿主的反应 通过将胰岛封装在新型纳米级生物材料层中的失败。通过发展 通过受控的稳定胶囊比标准实践小1000倍 胰岛表面上各个聚合物层的共价链接，空体积为 急剧减少，营养转运和葡萄糖感应不受影响。 纳米级层不仅是免疫植入物的一种手段，而且还可以作为 具有优化组成，结构，厚度的巨大潜力，并且 这些层在纳米水平上的功能。一旦捏造，这些纳米级 层是束缚功能剂，蛋白质或标记的理想平台 能够在植入物宿主接口上动态相互作用。因此，惰性 生物材料层可以转化为能够主动改变的生物活性表面 局部植入环境。在此提案中，我们试图束缚活跃 免疫调节蛋白/酶，抗炎剂和/或植入 - 增强纳米颗粒到纳米层表面。有效策略的设计 在胰岛表面上构建量身定制的纳米层 植入剂可以显着提高移植功效和长期稳定性。 这项研究的公共卫生影响是，这种方法可能会提供 通过减少或 完全消除了对免疫抑制疗法的需求并改善了长期 术语植入功能。