Implantable Electrospun Cell Chamber Device with Immune-Evasive Properties for Beta Cell Replacement Therapy

Type 1 diabetes (T1D) is a disease caused by destruction of pancreatic beta cells (-cells) due to an auto- immune response. T1D exerts a tremendous burden on quality of life for patients, and leads to a wide range of serious lifelong health consequences. T1D also places a tremendous economic burden on health care systems. The market for treatment of T1D is expected to reach $29 billion by 2029. Current treatments for T1D include insulin injections/infusions, pancreas transplant, or transplantation of isolated pancreatic islets of Langerhans for replacement of -cells. Replacement of the -cells by pancreas or pancreatic islets transplantation is a highly promising approach to T1D treatment, but is limited by a scarcity of donors. Furthermore, protection of the cells from the host immune system by immunosuppressive drugs is still required to avoid transplant rejection. To avoid the need for immunosuppression, efforts have been made to encapsulate isolated islets or -cells in an immune– protected environment. Although some promising results have been reported, thick fibrotic tissue formation around the encapsulation device has remained a persistent problem. The fibrotic capsule may block release of insulin and cause nutrient limitation and hypoxic conditions within the device, leading to -cell death and subsequent device failure. Furthermore, devices that do not provide adequate immune protection for the encapsulated cells still require lifelong immunosuppression of patients. This Phase I SBIR proposal will evaluate a novel electrospun (e-spun) cell chamber (Bio-Spun™ Cell Chamber or BSCC). Due to the unique nanofiber nature of e-spun materials, the device does not induce thick fibrotic capsule formation following implantation. A cell barrier layer within the device offers an immune-protected environment that supports growth and long-term maintenance of cells inside the chambers without immunosuppression. The BSCC device will be loaded with freshly isolated human pancreatic islets (hPI) containing functional pancreatic -cells, and the BSCC-hPI will be tested for glucose-stimulated insulin secretion, biocompatibility and efficacy for providing insulin independence following implantation in a diabetic rat model. The milestone for successful completion of these aims will be efficacy for providing insulin independence in diabetic rats for 60 days (primary endpoint) and demonstration of biocompatibility of the BSCC-hPIs with the host animals, including engraftment of heathy, non-fibrotic tissue into the outer layer of the BSCC device (secondary endpoint). The BSCC-hPI device is expected to overcome two major shortfalls (i.e., need for lifelong immunosuppression drugs, and lack of biocompatibility of currently available encapsulation devices) encountered to-date with attempts at -cell replacement therapy. Successful completion of these aims will demonstrate the feasibility for advancement of the project to more comprehensive Phase II SBIR biocompatibility and efficacy studies to be conducted in a diabetic porcine model. These will be followed by human clinical trials, and introduction of the BSCC-hPI device into the clinical marketplace as an important new treatment option for T1D patients.