DEVELOPMENT OF A BIOARTIFICIAL KIDNEY

已经实现了肾衰竭的长期离体治疗， 肾脏可能是第一个组织工程 概念可以产生用于长期体内植入的可植入装置 替代疗法 为了取代肾脏的排泄功能， 可植入的生物人工肾既需要一种装置来替代血液， 通过肾小球进行的超滤和替代装置 肾小管的运输调节功能。 我们已经开发 能够实现这些功能的早期原型设备。 第一阶段的努力 将通过确定以下方面的最佳组合来巩固这些努力 合成材料、生物化合物和细胞成分， 植入式生物人工肾 一个生物人造肾小球将 使用两种不同的方法制作。 一种方法是促进 使用血管生成因子促进靶向血管生成 聚砜中空纤维周围的毛细生长 渗透性，但具有高反射系数的蛋白质更大 超过25,000道尔顿 第二种方法是促进 自体内皮细胞单层生物反应器沿着内 聚砜中空纤维表面。 计划进行实验以测试 这两种方法的功能能力，以取代肾过滤。 这项建议的最终目标是发展初步的功能 含有过滤器的可植入生物人工肾的原型 设备连接到小管处理单元。 第一阶段赠款将 为第二阶段赠款奠定关键基础， 用于替代终末期患者肾功能的植入式装置 肾脏疾病，以避免长期透析治疗的需要，或 肾移植

Long term ex vivo therapy for kidney failure has been achieved, so that the kidney may be the first solid organ in which tissue engineering concepts can produce an implantable device for long-term in vivo replacement therapy. To replace the kidney's excretory function, an implantable bioartificial kidney requires both a device to replace blood ultrafiltration performed by renal glomeruli and a device to replace transport regulatory function of the renal tubule. We have developed early prototypic devices capable of these functions. The Phase I efforts will consolidate these efforts by identifying the best combination of synthetic materials, biologic compounds and cell components to produce an implantable bioartificial kidney. A bioartificial glomerulus will be produced using two different approaches. One approach is to promote targeted angiogenesis with the use of angiogenic factors to promote capillary growth around polysulfone hollow fibers with high hydraulic permeability but with a high reflection coefficient for proteins greater than 25,000 daltons. A second approach is to promote confluent growth in bioreactors of autologous endothelial cell monolayers along the inner surface of polysulfone hollow fibers. Experiments are planned to test the functional capacity of these two approaches to replace renal filtration. The ultimate goal of this proposal is to develop the initial functioning prototypes of an implantable bioartificial kidney containing a filtration device connected to a tubule processing unit. This Phase I grant will develop a critical foundation for the Phase II grant which will develop an implantable device to replace renal function in patients with end stage renal disease to circumvent the need for long-term dialytic therapy or renal transplantation.