Functionalized, Nanoscale Coatings for Islet Encapsulation

资助金：RFA-DK-08-001 标题：用于胰岛封装的功能化纳米涂层 少年派：切丽·斯泰勒 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，它是由于以下的胰岛功能受损和丢失而受到抑制的 植入。这种损失归因于强烈的炎症和免疫反应。 对移植，主要是由于细胞表面的炎性蛋白和抗原。在这 建议，我们寻求将导致胰岛植入的有害宿主反应降至最低 将胰岛包裹在新的纳米级生物材料层中而失败。通过开发 稳定的胶囊比标准做法小1000倍，通过受控 胰岛表面上单个聚合物层的共价连接，空隙体积为 显著减少，营养转运和葡萄糖传感不受影响。 纳米层不仅可以作为免疫伪装植入物的手段，而且还可以 具有巨大的潜力来优化成分、结构、厚度和 这些层在纳米级别上的功能。一旦制造出来，这些纳米级的 层是连接功能试剂、蛋白质或标记的理想平台 能够在植入物-主机界面处动态地相互作用。因此，惰性 生物材料层可以转化为生物活性表面，能够主动改变 局部化的种植环境。在这项提议中，我们寻求将积极的 免疫调节蛋白/酶、抗炎药和/或植入- 增强纳米颗粒对纳米层表面的作用。设计有效的战略来 在胰岛表面构建能够表达活性亲和素的量身定制的纳米层 植入剂能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，这种方法可能会提供一种 显著改善当前临床胰岛移植结果的手段，通过减少或 完全消除了免疫抑制治疗的需要，并改善了长期 术语植入功能。

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.