Research Project
9107450
? 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.
