An Intravascular Bioartificial Pancreas (iBAP)

 描述(申请人提供)：大约300万美国人和全世界大约2400万人受到1型糖尿病(T1D)的影响。血糖监测、外源性胰岛素注射、同种异体器官胰腺移植和同种异体胰岛移植是治疗T1D最常见的治疗方法。这些治疗对许多患者达到了血糖控制，但导致了严重的并发症。生物人工胰腺是一种 T1D是一种有希望的治疗方法，因为它含有功能性胰岛。不幸的是，之前开发BAP的尝试因胰岛腔内传质不足而受到严重限制。Silicon Kidney的创始人开发了硅纳米孔膜(SNM)，以实现高效的血液超滤，同时选择性地保留特定的溶质 对于生物人工肾项目和这个项目的成功可以直接转移到 IBAP。SNM的超高水力渗透特性将使胰岛腔内进行适当的质量传输(特别是氧气、葡萄糖和胰岛素)，以实现最佳的胰岛性能，而SNM的超选择性特性将实现前所未有的免疫隔离。IBAP将在动脉和静脉移植物之间连接，穿过胰岛腔的压力降将在胰岛腔内产生超滤液流动。超滤液将营养物质(特别是氧气和葡萄糖)对流地输送到胰岛腔，并将胰岛素输送到血液通道。我们项目的长期目标是创造血管内生物人工胰腺(IBAP)，以实现1型糖尿病(T1D)的外源性胰岛素非依赖性血糖控制。这个第一阶段的SBIR项目将通过在体外展示合适的胰岛小室性能和在体内展示IBAP的血液相容性来证明IBAP的可行性。

 DESCRIPTION (provided by applicant): Approximately 3 million Americans and around 24 million people worldwide are affected by Type 1 Diabetes (T1D). Glucose monitoring followed by exogenous insulin injection, allogeneic whole organ pancreas transplantation, and allogeneic islet transplantation are the most common treatments for T1D. These treatments have achieved glycemic control for many patients but result in serious complications. A bioartificial pancreas is a promising treatment for T1D because it contains functional islets. Unfortunately previous attempts at BAP development have been severely limited by insufficient mass transfer within the islet chamber. The founders of Silicon Kidney have developed silicon nanopore membranes (SNM) to achieve high-efficiency blood ultrafiltration while selectively retaining specific solutes for the Bioartificial Kidney Project and this project's successes are directly transferrable to the iBAP. The ultra-high-hydraulic-permeable characteristic of the SNM will enable appropriate mass transport (especially oxygen, glucose, and insulin) within the islet chamber to achieve optimal islet performance, while the ultra-selective characteristic of the SNM enable unprecedented immunoisolation. The iBAP will be connected between an arterial and venous graft and a pressure drop across the Islet Chamber will produce an ultrafiltrate flow within the Islet Chamber. The ultrafiltrate will provide convective mass transport of nutrients (especially oxygen and glucose) to the Islet Chamber and insulin to the blood channels. The long-term objective of our project is to create the intravascular Bioartificial Pancreas (iBAP) to achieve exogenous insulin independent glycemic control of Type 1 Diabetes (T1D). This Phase I SBIR project will prove the feasibility of the iBAP by demonstrating proper Islet Chamber performance in vitro and iBAP hemocompatibility in vivo.