3D Nanoporous microcontainers for cell encapsulation therapy

描述(申请人提供)：细胞包囊疗法(CET)提供了一种诱人的方法来移植细胞(同种或异种移植)，而不需要免疫抑制。通常，细胞包膜剂通过将细胞包裹在人工、半渗透的纳米孔大小排除膜周围来保护细胞免受免疫排斥反应，这种膜允许营养物质和治疗分子选择性地渗透到细胞和从细胞中渗透，同时防止免疫系统的成分攻击被包裹的细胞。尽管有相当大的兴趣和几项临床试验，该技术仍受到一系列挑战的限制，包括缺乏重复性；无法在形状、大小、形态和孔隙率方面制造统一的胶囊；由于曲折的孔隙率导致植入的胶囊剂产生生物污染；胶囊剂缺乏化学和机械稳定性；以及无法对移植细胞进行成像以监测疗效。其结果是，该领域的进展没有达到预期。我们开发了一种新型的纳升尺度的多孔容器，采用光刻制造和自组装相结合的方法。此外，我们已经获得了初步结果，这些结果提供了证据，证明可以制造出孔径小到20纳米的容器。这些容器具有优异的化学和机械稳定性，将生物降解的可能性降至最低；相同的形状、大小和精确的体积控制，将促进可预测的剂量并提高移植的重复性；以及已知不太容易受到生物污染的直接单分散孔隙率。此外，由于集装箱是金属的，它们与远程电磁场相互作用，从而可以使用磁共振成像(MRI)和计算机断层扫描(CT)等射频仪器对其进行非侵入性监测、控制和成像。我们建议在制备纳米孔(20 nm孔)容器的初步工艺的基础上，促进其在CET中的应用。我们还建议评估纳米孔容器在从包裹的胰岛细胞输送胰岛素方面的体外效果。纳米多孔、金属、自组装容器代表了一种全新的精密工程密封剂，将克服目前CET中使用的设备的局限性。CET与公共卫生高度相关，因为它为糖尿病、血友病、癌症、肾功能衰竭和帕金森氏症等一系列疾病提供了一系列有前途的治疗方法。我们建议制造纳米多孔、金属、自组装容器，这代表了一种全新的精密工程细胞密封剂，将克服目前用于细胞封装治疗(CET)的设备的局限性。CET与公共卫生高度相关，因为它为糖尿病、血友病、癌症、肾功能衰竭和帕金森氏症等一系列疾病提供了一系列有前途的治疗方法。

DESCRIPTION (provided by applicant): Cell encapsulation therapy (CET) provides an attractive means to transplant cells (allo- or xenotransplantation) without the need for immunosuppression. Typically, the cell encapsulant protects the cells from immune rejection by surrounding them with an artificial, semipermeable nanoporous size exclusion membrane that allows selective permeation of nutrients and therapeutic molecules to and from cells while preventing elements of the immune system from attacking the encapsulated cells. Despite considerable interest and several clinical trials, the technology is limited by a range of challenges including a lack of reproducibility; the inability to fabricate uniform capsules in terms of shape, size, morphology, and porosity; biofouling of implanted encapsulants due to tortuous porosity; the lack of chemical and mechanical stability of the encapsulants; and the inability to image transplanted cells to monitor efficacy. The result is that progress in the field has not lived up to expectations. We have developed a new class of nanoliter scale, porous containers using a combination of lithographic fabrication and self-assembly. Additionally, we have obtained preliminary results that provide evidence that containers with a pore size as small as 20 nm can be fabricated. The containers have excellent chemical and mechanical stability, minimizing the possibility of biodegradation; identical shapes, sizes and precise volumetric control that will facilitate predictable dosages and improve reproducibility in transplantation; and straight monodisperse porosity that is known to be less susceptible to biofouling. Moreover, since the containers are metallic, they interact with remote electromagnetic fields that allow them to be monitored, controlled and imaged non- invasively using radio frequency instrumentation such as magnetic resonance imaging (MRI) and computed tomography (CT). We propose to build on the preliminary process developed to fabricate nanoporous (20 nm pores) containers to facilitate their use in CET. We also propose to evaluate the in-vitro efficacy of the nanoporous containers in the delivery of insulin from encapsulated pancreatic islet cells. The nanoporous, metallic, self-assembled containers represent an entirely new class of precisely engineered encapsulants that will overcome the limitations of present day devices used in CET. CET is highly relevant to public health as it provides a range of promising therapeutic treatments for a wide range of diseases such as diabetes, hemophilia, cancer, renal failure, and Parkinson's disease. We propose to fabricate nanoporous, metallic, self-assembled containers that represent an entirely new class of precisely engineered cell encapsulants that will overcome the limitations of present day devices used in cell encapsulation therapy (CET). CET is highly relevant to public health as it provides a range of promising therapeutic treatments for a wide range of diseases such as diabetes, hemophilia, cancer, renal failure, and Parkinson's disease.