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.

项目概要 1 型糖尿病 (T1D) 影响着美国近 300 万人，全球超过 2000 万人。一个 部分患者患有不稳定的 T1D，因为他们的血糖控制不佳且存在严重低血糖 无意识。虽然全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 受到免疫抑制治疗和供体组织稀缺的限制。相反，将胰岛封装在 免疫保护膜是消除免疫抑制需求的一种有前途的方法，但是 之前的尝试因基于扩散的氧气、葡萄糖和胰岛素的传质率较低而受到影响。 设备。为了解决扩散的局限性，之前的小组测试了基于血管内对流的 设备并显示出一些希望，但它们提供的超滤率不足以提供足够的胰岛 氧合和葡萄糖-胰岛素动力学。相比之下，Silicon Kidney 正在将硅纳米孔商业化 膜 (SNM)，可产生高水平的超滤液（>10 倍于之前使用的聚合物膜） 基于超滤的 BAP 装置）在生理血压下，提供卓越的对流传质 启用功能性 BAP。为了进一步增强胰岛氧合，全氟化碳（高氧） 容量材料，可以合并到胰岛细胞支架中以模拟氧气的储存和释放 通过在胰岛的低耗氧状态下储存氧气来改变血红蛋白的特性 （空腹状态）并在胰岛的高耗氧状态（餐后）期间释放。在第一阶段 SBIR 中 项目中，我们将结合 SNM 支持的对流和基于全氟化碳的细胞支架 展示了前所未有的胰岛氧合和功能，同时减少了整体设备尺寸。