Pressure Management Technologies for Oxygenation of Implanted Insulin-Secreting Cells The overall goal of the SBIR project is to develop an advanced, miniaturized implantable electrochemical oxygen generator that supplies oxygen at well-regulated dose and concentration to cells within an immunoisolation device, so as to ensure their viability and function at high density and minimize overall implant size. The proposed Phase II program addresses several key areas of emphasis in this NIDDK special RFA. The core innovation is a patent-pending, self-regulating electrochemical gas generator (SREGG), which intrinsically manages the pressure of oxygen generated; this allows for careful control over oxygen dose, device simplicity and dependability. The SREGG will be the definitive oxygen generation module of the Giner bioartificial pancreas with implanted oxygen supply (BAPIOS?) system. The fully implantable BAPIOS? system includes the SREGG, cell capsule filled with glucose-regulating cells and power/control electronics; system recharging is via wireless transcutaneous energy transfer in the evenings. The BAPIOS? system development is taking place under separate Giner and NIDDK (R44DK100999) funding. Oxygenation of implanted cells is critical to maintaining viability and function at high cellular densities, minimizing overall implant size. The first proposed application of the Giner BAPIOS? system is a human pancreatic islet implant for treatment of type 1 diabetes (T1D), with future application to type 2 diabetes. The SREGG is also a platform technology that may be combined with various cell implant devices and therapeutic cell types for additional cell therapies. The BAPIOS? system includes a cell implant capsule with clinical testing and proven safety records, and will be fully implanted subcutaneously without infection-prone percutaneous tubes/leads. This approach is superior to allogenic pancreas or intraportal islet transplantation because it will involve simple surgery and avoids the cost and health hazards of long term systemic immunosuppression. Giner?s ultimate solution will leverage the most recent progress in stem cell-derived cell sourcing, obviating the need to procure allogeneic islets by donation and isolation. The BAPIOS? treatment will eliminate accumulated strain of standard insulin drug therapy (i.e., glycosylation of proteins and risk of sequelae due to frequent high blood sugar) by imparting natural glucose control; and the absence of worn pumps, frequent blood testing and injections promises renewed freedom and active lifestyles for T1D sufferers. In the Phase I project, significant progress was achieved in selection of materials and optimization of the SREGG cell design and construction. Excellent pressure regulation, cell efficiency and long-term performance were demonstrated in bench testing of several SREGG cell prototypes. Development of a novel, complementary current control chipset was also undertaken, and this circuitry showed high efficiency, reliability and amenability to substantial future miniaturization for implant applications. A detailed SREGG design was generated to transition the cell beyond feasibility toward implant testing in Phase II. The Phase II effort will further develop the SREGG cell for integration and implantation, design and fabricate electronic controls and pressure monitoring devices in support of preclinical tests, and demonstrate pressure control using the SREGG cell and associated bioartificial pancreas components in a small animal model, with the goal of achieving 30 days of glucose control in a diabetic rat model. Giner will subcontract with a medical device manufacturer to specify, derisk and fabricate advanced preclinical systems under ISO 13485 design control. Giner will additionally assemble a collaborative team to support and conduct animal studies, develop protocols for preclinical/clinical implementation, and perform in vivo and post-explant evaluations of the implanted devices. The program will also contribute to the body of scientific work toward the understanding of the metabolic and insulin secretion behavior of high purity human islets under the conditions of macroencapsulation.
The goal of the Phase II program is to optimize and integrate a novel, implantable electrochemical oxygen generator which has passive pressure and generation rate limiting capability, and thereby achieves fine control over oxygen dose while decreasing size and complexity of the implanted device. The oxygen produced will be a critical enabler of compact cell therapy implants. The priority application for this transformative platform technology is a pancreatic islet implant with the potential to cure diabetes. The biocompatibility and performance of the generator, as well as the efficacy of a combination of the implanted generator and encapsulated pancreatic islets, will be evaluated in small animal models.