A high oxygen capacity cell scaffold for the intravascular bioartifical pancreas (iBAP)

用于血管内生物人工胰腺（iBAP）的高氧容量细胞支架

• 批准号: 9899079
• 负责人: Charles Blaha
• 金额: $ 29.84万
• 依托单位: SILICON KIDNEY, LLC
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-19 至 2023-09-18
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9899079
• 关键词: Adult; Affect; American; Anastomosis - action; Area; Arteries; Award; Blood; Blood Pressure; Blood Vessels; Blood flow; California; Catheters; Cells; Consumption; Convection; Devices; Diffuse; Diffusion; Drops; Emulsions; Encapsulated; Family suidae; Fasting; Fluorocarbons; Geometry; Glucose; Grant; Healthcare Systems; Hemoglobin; Hour; Housing; Immunosuppression; Insulin; Insulin-Dependent Diabetes Mellitus; Islet Cell; Islets of Langerhans Transplantation; Kidney; Kinetics; Legal patent; Mechanics; Membrane; Modeling; National Institute of Diabetes and Digestive and Kidney Diseases; Nutrient; Organ; Outcome; Oxygen; Oxygen Consumption; Pancreas; Patients; Permeability; Phase; Physiological; Polymers; Production; Property; Quality of life; Safety; San Francisco; Silicon; Small Business Innovation Research Grant; Technology; Testing; Therapeutic immunosuppression; Tissue Donors; Transplantation; Ultrafiltration; United States; Universities; Veins; Venous; arm; base; cost; density; design; glycemic control; hemocompatibility; hypoglycemia unawareness; implantation; improved; innovation; islet; multidisciplinary; nanopore; off-patent; patient subsets; pressure; prototype; scaffold; scale up; type I diabetic

PROJECT SUMMARY Type 1 Diabetes (T1D) affects nearly 3 million people in the United States over 20 million people globally. A subset of patients have unstable T1D because they possess poor glycemic control and severe hypoglycemia unawareness. While whole organ pancreas and islet transplantation can cure unstable T1D, these treatments are limited by immunosuppression therapy and scarcity of donor tissue. In contrast, encapsulating islets within an immunoprotecting membrane is a promising approach to eliminate the need for immunosuppression, but previous attempts suffered from low mass transfer rates of oxygen, glucose, and insulin in diffusion-based devices. In order to solve the limitations of diffusion, previous groups tested intravascular convection-based devices and showed some promise, but they provided insufficient ultrafiltration rates to provide sufficient islet oxygenation and glucose-insulin kinetics. In contrast, Silicon Kidney is commercializing the silicon nanopore membrane (SNM), which produces high levels of ultrafiltrate (>10x polymer membranes used in previous ultrafiltrate-based BAP devices) at physiologic blood pressures, providing exceptional convective mass transfer enabling a functional BAP. To further enhance islet oxygenation, perfluorocarbons, which are high oxygen capacity materials, can be incorporated into the islet cell scaffold to mimic the oxygen storage and release properties of hemoglobin by allowing oxygen to be stored during the islet’s low oxygen consumption state (fasting state) and released during the islet’s high oxygen consumption state (post-meal). In this Phase I SBIR project, we will combine the SNM-enabled convection and a perfluorocarbon-based cell scaffold to demonstrate unprecedented islet oxygenation and function, while allowing a reduction in overall device size.

项目摘要 1型糖尿病（T1D）在美国影响了近300万人，全球超过2000万人。一个 患者的子集具有不稳定的T1D，因为他们的血糖控制差和严重的低血糖 不知情。虽然整个器官胰腺和胰岛移植可以治愈不稳定的T1D，但这些治疗方法 受到免疫抑制疗法和供体组织的稀缺的限制。相反，将胰岛包装在 免疫保护膜是消除免疫抑制的必要方法，但 以前的尝试在基于扩散的基于扩散的氧，葡萄糖和胰岛素的传质速率低。 设备。为了解决扩散的局限性，先前的组测试了基于血管内连接的局限性 设备并表现出一些希望，但它们提供了不足的超滤率来提供足够的胰岛 氧合和葡萄糖胰岛素动力学。相比之下，硅肾正在商业化硅纳米孔 膜（SNM），产生高水平的超滤（>> 10倍的聚合物膜 在生理血压上，基于超滤光的BAP设备），提供了异常的对流传质 启用功能性BAP。为了进一步增强胰岛氧合，全氟化合物，高氧 容量材料可以将胰岛细胞支架纳入模拟氧气存储并释放 血红蛋白的特性通过允许在胰岛低氧状态下储存氧 （禁食状态）并在胰岛高氧消耗状态（后）发行。在这个阶段我 项目，我们将结合启用SNM的连接和全氟化合物的细胞支架 展示了前所未有的胰岛氧合和功能，同时允许降低整体设备尺寸。