A Hepadtodialysis Bioreactor as Mechanical Support of Liver Failure

肝病是发病的主要原因 and mortality. 肾透析， 彻底改变了肾脏疾病的治疗 失败，没有成功的肝脏 对应物。 这一提议的目的是 研究是为了开发一种技术， 有效的肝透析系统， 培养的肝细胞作为 "生物人工肝"。 私家侦探的很 开发新型中空纤维生物反应器， 其中肝细胞被包埋在基质中 在中空纤维的内腔中形成凝胶。 同时和持续提供 肝细胞的营养物质 在中空纤维腔内， 不断地沐浴在 纤维 这种设计允许水的透析 可溶性毒素-包括毒品- 促进其他人的新陈代谢， 肝细胞转化为代谢性肝细胞 然后用管腔移除的形式 养分流动 拟议的研究将 发展必要的工程知识 用于设计临床适用的 "生物人工"肝脏。 研究计划 包括三个阶段：1）定义 环境工程条件 其维持最佳的生物反应器功能; 2)使系统适应大规模使用 同系肝细胞; 3）大型动物试验 使用同种异体的 肝细胞 研究团队包括 具有工程专业知识的个人， 开发成功的生物反应器技术 以及肝细胞方面的生物学专业知识 培养和功能。

Liver disease is a major cause of morbidity and mortality. Renal dialysis, which revolutionized the treatment of renal failure, does not have a successful hepatic counterpart. The goal of this proposed research is to develop the technology for an effective hepatodialylsis system using cultured hepatocytes to function as a "bioartificial liver". The P.I.'s are developing a new hollow fiber bioreactor in which hepatocytes are entrapped in a matrix gel within the lumen of the hollow fibers. Simultaneous and continuous provision of nutrients to the hepatocytes also occurs within the hollow fiber lumens while blood continuously bathes the outer surface of the fibers. This design allows dialysis of water soluble toxins -- including drugs -- and facilitates the metabolism of others by the hepatocytes with conversion to metabolic forms that are then removed with the luminal nutrient flow. The proposed research will develop the engineering knowledge necessary for the design of a clinically applicable "bioartificial" liver. The research plan consists of three phases: 1) Defining environmental and engineering conditions which maintain optimal bioreactor function; 2) Adapting the system to large scale using syngeneic hepatocytes; 3) Large animal trials of the developed technology using allogeneic hepatocytes. The research team includes individuals with engineering expertise in developing successful bioreactor technology as well as biological expertise in hepatocyte cultivation and function.