3D Nanoporous microcontainers for cell encapsulation therapy

用于细胞封装治疗的 3D 纳米多孔微容器

基本信息

批准号：
7568185
负责人：
David H Gracias
金额：
$ 23.98万
依托单位：
JOHNS HOPKINS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-02-15 至 2010-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7568185
关键词：
Biochemical Biodegradation Cell Therapy Cell Transplants Cells Characteristics Chemicals Clinical Clinical Trials Defect Devices Diabetes Mellitus Diffusion Disease Electromagnetic Fields Electron Microscopy Elements Encapsulated Engineering Environment Exclusion Face Frequencies Glucose Hemophilia A Image Immune Immune response Immune system Immunoglobulin G Immunosuppression Implant In Vitro Insulin Islet Cell Islets of Langerhans Kidney Failure Life Literature Magnetic Resonance Imaging Malignant Neoplasms Mechanics Membrane Monitor Morphology Nutrient Operative Surgical Procedures Optics Parkinson Disease Polystyrenes Porosity Process Property Public Health Publishing Radio Reproducibility Research Shapes Technology Therapeutic Time Translating Transplantation Universities X-Ray Computed Tomography Xenograft procedure biomaterial compatibility capsule cellular engineering chemical stability diabetes mellitus therapy dosage expectation implantation improved instrumentation interest minimally invasive nanolitre nanolitre scale prevent research study self assembly simulation

项目摘要

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.

描述（由申请人提供）：细胞封装疗法（CET）为移植细胞（同种或异种移植）提供了一种有吸引力的方法，而无需免疫抑制。通常，通过用人工，可半透明的纳米多孔尺寸排除膜环绕细胞，可以保护细胞免疫排斥，从而可以选择性地渗透营养物质和治疗分子到和免受细胞的渗透，同时防止免疫系统的元素攻击包含的细胞。尽管有很大的兴趣和几项临床试验，但该技术仍受到一系列挑战的限制，包括缺乏可重复性。无法在形状，大小，形态和孔隙率方面制造均匀的胶囊；由于曲折的孔隙度而生物染色的封装剂；封装物缺乏化学和机械稳定性；以及无法成像移植细胞以监测功效。结果是该领域的进步尚未达到预期。我们已经开发了一种新的纳米尺度，即使用光刻制造和自组装的多孔容器。此外，我们获得了初步结果，这些结果提供了证据，表明可以制造孔径小至20 nm的容器。容器具有出色的化学和机械稳定性，最大程度地降低了生物降解的可能性。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可重复性；和直的单分散孔隙率不易生物污染。此外，由于容器是金属的，因此它们与远程电磁场相互作用，这些电磁场可以使用磁共振成像（MRI）和计算机断层扫描（CT）进行监测，控制和成像的远程电磁场。我们建议建立在制造纳米孔（20 nm孔）容器以促进其在CET中使用的初步过程。我们还建议评估纳米多孔容器在从包裹的胰岛细胞中传递胰岛素时的体外功效。纳米孔，金属，自组装的容器代表了一类全新的精确封装，将克服CET中使用的当今设备的局限性。 CET与公共卫生高度相关，因为它为糖尿病，血友病，癌症，肾衰竭和帕金森氏病等多种疾病提供了一系列有希望的治疗疗法。我们建议制造纳米方面的，金属的，自组装的容器，这些容器代表一类全新的精确的细胞包装剂，这些封装将克服细胞包封疗法（CET）中使用的当今设备的局限性。 CET与公共卫生高度相关，因为它为糖尿病，血友病，癌症，肾衰竭和帕金森氏病等多种疾病提供了一系列有希望的治疗疗法。

项目成果

期刊论文数量（5）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Size selective sampling using mobile, 3D nanoporous membranes.

DOI：
10.1007/s00216-008-2538-2
发表时间：
2009-02
期刊：
ANALYTICAL AND BIOANALYTICAL CHEMISTRY
影响因子：
4.3
作者：
Randall, Christina L.;Gillespie, Aubri;Singh, Siddarth;Leong, Timothy G.;Gracias, David H.
通讯作者：
Gracias, David H.

Dual-Gel 4D Printing of Bioinspired Tubes