Bioreactors for hybrid liver support: historical aspects and novel designs

A novel bioreactor construction has been designed for the utilization of hepatocytes and sinusoidal endothelial cells. The reactor is based on capillaries for hepatocyte aggregate immobilization. Three separate capillary membrane systems, each permitting a different function are woven in order to create a three dimensional network. Cells are perfused via independent capillary membrane compartments. Decentralized oxygen supply and carbon dioxide removal with low gradients are possible. The use of identical parallel units to supply hepatocytes facilitates scale up. In vitro studies demonstrate long-term external metabolic function in primary isolated hepatocytes within bioreactors. These systems are capable of supporting essential liver functions. Animal experiments have verified the possibility of scaling-up the bioreactors for clinical treatment. However, since there is no reliable animal model for investigation of the treatment of acute liver failure, the promising results obtained from these studies have limited relevance. The small number of clinical studies performed so far is not sufficient to reach conclusions about improvements in the therapy of acute liver failure. Although important progress has been made in the development of these systems, various hepatocyte culture models and bioreactor constructions are being discussed in the literature, which indicates competition in this field of medical research. An overview, which emphasizes the development of hepatocyte culture models for bioreactors, subsequent in vitro studies, animal studies, and clinical application, is also provided.