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

项目摘要 1型糖尿病（T1 D）影响美国近300万人，全球超过2000万人。一 由于血糖控制不良和严重低血糖，一部分患者患有不稳定型T1 D 无知虽然整个器官胰腺和胰岛移植可以治愈不稳定的T1 D，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。相比之下， 免疫保护膜是消除免疫抑制需要的有希望的方法，但是 先前的尝试遭受了基于扩散的氧气、葡萄糖和胰岛素的低传质速率 装置.为了解决扩散的局限性，之前的研究小组测试了基于血管内对流的 设备，并显示出一些承诺，但他们提供了不足的超滤率，以提供足够的胰岛 氧合和葡萄糖-胰岛素动力学。相比之下，硅肾公司正在将硅纳米孔商业化 膜（SNM），其产生高水平的超滤液（> 10倍的聚合物膜，用于以前的 基于超滤的BAP装置），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， 容量材料，可以并入胰岛细胞支架中以模拟氧储存和释放 通过允许在胰岛的低氧消耗状态期间储存氧气来改善血红蛋白的性质 在胰岛的高耗氧状态（餐后）期间释放。在本阶段I SBIR中， 项目，我们将结合联合收割机的SNM启用对流和全氟化碳为基础的细胞支架， 显示出前所未有的胰岛氧合和功能，同时允许减小整体装置尺寸。

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.