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

1型糖尿病（T1 D）是由胰腺β细胞（β细胞）的破坏引起的疾病， 免疫反应T1 D对患者的生活质量造成巨大负担，并导致广泛的 严重的终身健康后果。T1 D也给卫生保健系统带来巨大的经济负担。 T1 D治疗市场预计到2029年将达到290亿美元。目前T1 D的治疗方法包括 胰岛素注射/输注、胰腺移植或分离的胰岛移植， 更换电池。用胰腺或胰岛移植替代胰岛细胞是一种高度有效的方法， 这是一种很有前途的T1 D治疗方法，但受到供体稀缺的限制。此外，保护细胞 从宿主免疫系统的免疫抑制药物仍然需要，以避免移植排斥。避免 由于免疫抑制的需要，已经努力将分离的胰岛或胰岛细胞包封在免疫- 保护环境。虽然已经报道了一些有希望的结果，但厚纤维化组织形成 在封装装置周围仍然是一个持续的问题。纤维化囊可以阻断 胰岛素，并在装置内引起营养限制和缺氧条件，导致胰岛细胞死亡， 后续设备故障。此外，不能为受试者提供足够免疫保护的装置， 包封的细胞仍然需要患者终身免疫抑制。第一阶段SBIR提案将评估 新型电纺（e-spun）细胞室（Bio-Spun™ Cell Chamber或BSCC）。由于其独特的 由于静电纺丝材料的性质，该装置在植入后不会诱导厚纤维化囊形成。一 设备内的细胞屏障层提供了一个支持生长和长期的免疫保护环境 在没有免疫抑制的情况下维持腔室内的细胞。BSCC设备将加载 新鲜分离的人胰岛（hPI）含有功能性胰腺β细胞，并且BSCC-hPI将是 测试了葡萄糖刺激的胰岛素分泌、生物相容性和提供胰岛素非依赖性的功效 植入糖尿病大鼠模型后。成功实现这些目标的里程碑将是 在糖尿病大鼠中提供胰岛素非依赖性60天的功效（主要终点）和证明 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宿主动物中， BSCC器械的外层（次要终点）。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，并且目前缺乏生物相容性， 可用的包封装置）。成功 这些目标的完成将证明该项目推进到更全面的可行性。 将在糖尿病猪模型中进行II期SBIR生物相容性和功效研究。这些将是 随后进行人体临床试验，并将BSCC-hPI装置作为一种 T1 D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.