High Cell Density Bioartificial Pancreas Enabled by Implantable Oxygen Generator

 描述(由申请人提供)：可植入氧气发生器实现的高细胞密度生物人工胰腺SBIR项目的总体目标是开发和测试具有可植入氧气供应的人体规模的生物人工胰腺(BAPIOS(Tm))。这包括一个微型植入式电化学氧气发生器(EOG)，它将持续向免疫隔离细胞植入设备中的胰岛或？细胞供应氧气。氧合在高细胞密度下维持细胞的活性和功能，最大限度地减少植入物的总尺寸。该平台技术的第一个拟议应用是用于治疗1型糖尿病(T1D)的人胰岛植入物。植入式EOG也是一种平台技术，可以与各种细胞植入设备和治疗性细胞类型相结合，用于肝功能衰竭、帕金森病、甲状腺疾病和胰腺切除术等适应症的额外细胞治疗。Giner BAPIOS(Tm)系统包括一个细胞植入胶囊，该胶囊具有临床测试和经过验证的安全记录。BAPIOS(Tm)系统将被完全植入皮下，不需要容易感染的经皮管/引线。门脉内胰岛同种异体肝移植(IPIATx)是治疗T1D患者的一种很有前途的治疗方法。领先中心的结果显示，50%的受者胰岛素独立5年以上；这接近复杂的全胰腺移植的成功率，但IPIATx目前需要2-3名捐赠者的胰岛。胰岛移植治疗T1D的广泛临床应用受到关键障碍的阻碍，这些障碍包括：1)当前移植部位需要全身免疫抑制；2)人类胰岛组织供应有限(每年&lt；5000美国胰腺捐赠者)。生物兼容、可回收的细胞分离设备的使用解决了这些关键障碍，因为它能够在没有免疫抑制的情况下更有效和高效地使用同种异体胰岛，并最终使用葡萄糖反应和胰岛素分泌细胞的替代来源。在Phi项目中，在大鼠模型中明确证明了氧气是维持高密度植入物(每平方厘米8000个人胰岛当量(IE))的生存和功能所必需的。结果还显示，在该动物模型中，皮下包埋充氧植入物逆转糖尿病的胰岛(边缘质量较低)比文献中肝或肾包膜部位的结果要少。设计和制造了微型EOG；测试表明，足够的氧气支持人类植入预期的胰岛剂量。PhII项目的结果将是第一个具有植入性氧气供应的生物人工胰腺。PhII Giner BAPIOS(Tm)系统将采用模块化设计，包括：a)可植入人体规模的EOG，具有生物兼容性和获取体水的新规定；b)利用经皮能量转移的电力系统；c)专为氧气输送而定制的细胞胶囊(TheraCyte(Tm))。该计划的结论是：1)对完全可植入的PHI系统进行临床前试验；2)为未来的实施和临床测试完成Giner BAPIOS(Tm)系统的人体临床模型设计。

 DESCRIPTION (provided by applicant): High Cell Density Bioartificial Pancreas Enabled by Implantable Oxygen Generator The overall goal of the SBIR project is to develop and test a human scale BioArtificial Pancreas with Implantable Oxygen Supply (BAPIOS(tm)). This consists of a miniaturized implantable electrochemical oxygen generator (EOG) that will continuously supply oxygen to islets or ß-cells within an immunoisolation cell implant device. Oxygenation maintains cell viability and function at high cellular densities, minimizing overall implant size. The first proposed application of this platform technology is a human pancreatic islet implant for the treatment of Type 1 diabetes (T1D). The implantable EOG is also a platform technology that may be combined with various cell implant devices and therapeutic cell types for additional cell therapies for indications such as liver failure, Parkinson's disease, (para)thyroid disease and pancreatectomy. The Giner BAPIOS(tm) system includes a cell implant capsule with clinical testing and proven safety records. The BAPIOS(tm) system will be fully implanted subcutaneously without infection-prone percutaneous tubes/leads. Intraportal Pancreatic Islet Allogeneic Transplantation (IPIATx) liver is emerging as a promising treatment for select T1D patients. Results from leading centers demonstrate insulin independence for more than 5 years for 50% of the recipients; this approaches the success rate of a complex whole pancreas transplant, but IPIATx currently requires islets from 2-3 donors. Widespread clinical application of islet transplantation for T1D is hindered by critical barriers including: 1) the need for systemic immunosuppression for the current transplant site; and 2) the limited supply of human islet tissue (<5,000 U.S. pancreas donors per year). The use of biocompatible, retrievable, cell isolating devices addresses these critical barriers by enabling the more effective and efficient use of allogeneic islets without immunosuppression and the eventual use of alternative sources of glucose-responsive, insulin-secreting cells. In the PhI project, it was definitively demonstrate in a rat model that oxygen is necessary to allow the viability and function of a high density implant (8,000 human islet equivalents (IE) per cm2). The results also showed that subcutaneous encapsulated oxygenated implants reversed diabetes with fewer islets (lower marginal mass) than literature results for the liver or kidney capsule sites in this animal model. miniature EOG was designed and fabricated; testing demonstrated more than sufficient oxygen for supporting the islet dose anticipated for human implant. The outcome of the PhII project will be the first bioartificial pancreas with implantable oxygen supply. The Ph II Giner BAPIOS(tm) system will have a modular design including: a) an implantable human scale EOG with novel provisions for biocompatibility and access to body water; b) a power system utilizing transcutaneous energy transfer; and c) an established cell capsule (TheraCyte(tm)) tailored for oxygen delivery. The program concludes with: 1) preclinical trial testing the fully implantable PhI system; and 2) complete design for the human clinical model of the Giner BAPIOS(tm) system for future implementation and clinical testing.