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

1型糖尿病(T1D)是一种胰岛β细胞(细胞)破坏引起的疾病，其原因是自身 免疫反应。T1D给患者的生活质量带来了巨大的负担，并导致了广泛的 严重的终身健康后果。T1D还给卫生保健系统带来了巨大的经济负担。 到2029年，治疗T1D的市场预计将达到290亿美元。目前治疗T1D的方法包括 胰岛素注射/输注、胰腺移植或孤立的朗格汉斯胰岛移植 细胞的更替。用胰腺或胰岛移植替代细胞是一种高度有效的方法 T1D治疗的前景看好，但受到捐赠者稀缺的限制。此外，对细胞的保护 仍需通过免疫抑制药物从宿主免疫系统中避免移植排斥反应。为了避免 由于免疫抑制的需要，人们已经努力将分离的胰岛或细胞包裹在免疫- 受保护的环境。尽管已经报道了一些有希望的结果，但厚重的纤维组织形成 围绕封装设备的问题一直是个老大难问题。纤维化胶囊可能会阻碍药物的释放 胰岛素和引起营养限制和设备内的低氧条件，导致细胞死亡和 随后的设备故障。此外，不能提供足够的免疫保护的设备 被包裹的细胞仍然需要患者终身免疫抑制。此第一阶段SBIR建议书将评估 一种新型的电纺(e纺)电池室(生物纺丝™电池室或BSCC)。由于独特的纳米纤维 由于电子纺丝材料的性质，该设备在植入后不会导致厚厚的纤维性囊膜形成。一个 设备内的细胞屏障层提供了免疫保护的环境，支持生长和长期 在没有免疫抑制的情况下维持小室内的细胞。BSCC设备将加载 新鲜分离的含有功能性胰腺-细胞的人胰岛， 测试葡萄糖刺激的胰岛素分泌、生物相容性和提供胰岛素独立性的有效性 在糖尿病大鼠模型中植入后。成功完成这些目标的里程碑将是 为糖尿病大鼠提供60天胰岛素非依赖性的有效性(主要终点)和示范 BSCC-HPI与宿主动物的生物相容性，包括将健康的非纤维化组织植入 BSCC设备的外层(辅助端点)。BSCC-HPI设备预计将克服两个 主要不足(即，需要终身免疫抑制药物，以及目前缺乏生物相容性 可用的封装设备)在细胞替代疗法的尝试中遇到。成功 这些目标的完成将证明项目推进到更全面的可行性 将在糖尿病猪模型中进行第二阶段SBIR生物兼容性和有效性研究。这些将是 随后是人体临床试验，并将BSCC-HPI设备作为一种 T1D患者的重要新治疗选择。

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.