High Cell Density Bioartificial Pancreas Enabled by Implantable Oxygen Generator

描述（由申请人提供）：这个拟议的SBIR项目的总体目标是开发一种微型植入式氧气发生器，它将持续向免疫隔离细胞植入装置内的细胞供应氧气。这将在高细胞密度下保持细胞活力和功能，从而使植入体的整体尺寸最小化。氧气发生器将由远程充电电池供电。该平台技术的第一个应用是胰岛植入治疗1型糖尿病（T1D）。氧合器与特性良好的免疫隔离装置的结合称为植入式供氧生物人工胰腺（BAPIOS）。植入式氧气发生器也是一种平台技术，可以与其他细胞植入设备和其他治疗细胞类型相结合，用于肝衰竭等疾病的其他细胞治疗，

DESCRIPTION (provided by applicant): The overall goal of this proposed SBIR project is to develop a miniaturized implantable oxygen generator that will continuously supply oxygen to cells within an immunoisolation cell implant device. This will maintain cellular viability and function at high cell densities thus minimizing overall implant size. The oxygen generator will be powered by a remotely rechargeable battery. The first proposed application of this platform technology is pancreatic islet implant for the treatment of Type 1 diabetes (T1D). The combination of the oxygenator with a well-characterized immunoisolation device is termed a bioartificial pancreas with implantable oxygen supply (BAPIOS). The implantable oxygen generator is also a platform technology that could be combined with other cell implant devices and other therapeutic cell types for other cellular therapies for conditions such as liver failure, Parkinson's disease, (para)thyroid disease and hemophilia. Pancreatic islet allotransplantation is in U.S. clinical trials. There are also results from leading centers demonstrating insulin independence for more than 5 years for 50% of the recipients. However, widespread clinical application of for T1D is hindered by two critical barriers: 1) the need for systemic immunosuppression for the current intraportal liver transplant site; and 2) by the finite and low supply of human islet tissue (a few thousand suitable donors per year). The use of biocompatible, retrievable, cell isolating devices may address these critical barriers by enabling the more effective and efficient use of allogeneic islets without immunosuppression and the eventual use of stem cell-derived or xenogeneic islets with minimum or no immunosuppression. Autotransplantation (for pancreatitis patients and pre-cancer diagnosis) could also benefit from a simple implant procedure with retrievability and cellular immunoisolation. Current cell implant devices have insufficient oxygen (even with prevascularization of the device) to provide the high cellular densities required for practically-sized clinical implants. The proposed technology would include the first implantable, continuous oxygen supply with integrated rechargeable battery. The Specific Aims of the 12 month Phase I project are: Aim 1: Design and fabrication of a miniature oxygen generator (oxygenator); Aim 2: In vitro evaluation of the Ph I miniature oxygenator and the oxygenated implant device; Aim 3: Preliminary in vivo testing in a diabetic nude rat model; and Aim 4: Design of complete bioartificial pancreas with implantable oxygen supply (BAPIOS) for implementation in Ph II. This aim includes a fully implantable oxygenator as well as customization of the cell implant device for this application. This Ph I feasibility stuy will provide the groundwork for final design and fabrication of a fully implantable oxygenated cell implant in Phase II and large animal studies ultimately leading to the treatment of T1D in humans.