A Hepadtodialysis Bioreactor as Mechanical Support of Liver Failure

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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.