Functionalized, Nanoscale Coatings for Islet Encapsulation

授权：RFA- DK-08-001 标题：用于胰岛封装的功能化纳米涂层 PI：Cherie Stabler 项目摘要 虽然临床胰岛移植（CIT）已显示出治疗1型糖尿病的前景， 糖尿病，它是由受损的功能和损失的胰岛以下 置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 建议，我们寻求最大限度地减少有害的宿主反应，导致胰岛移植 通过将胰岛包封在新型纳米级生物材料层中而失败。发展中 通过控制， 胰岛表面上的单个聚合物层的共价连接， 显著减少，营养转运和葡萄糖感知不受影响。 纳米级层不仅作为一种手段，免疫移植，而且 具有优化成分、结构、厚度的巨大潜力， 这些层在纳米水平上的功能。一旦制造出来，这些纳米级的 层作为理想的平台，用于束缚功能剂、蛋白质或标记物 能够在植入物-宿主界面处动态地相互作用。因此，惰性 生物材料层可以转化为能够主动改变生物活性的生物活性表面。 局部植入环境。在这个提议中，我们试图将活跃的 免疫调节蛋白质/酶、抗炎剂和/或植入物- 增强纳米颗粒到纳米层表面。制定有效的战略， 在胰岛表面构建能够表达活性前体的定制纳米层， 植入剂可以显著提高移植效率和长期稳定性。 这项研究对公共卫生的影响是，这种方法可能提供一种 显著改善目前临床胰岛移植结果的手段， 完全消除了对免疫抑制治疗的需要，并改善了长期- 术语植入物功能。

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.