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. ? ? ?
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