Liver, Bio-Artificial

The liver is one of the most complex and metabolically active organs in the body and performs many detoxification and protein synthetic functions that are essential to life. Extracorporeal bioartificial liver (BAL) systems consisting of functioning, viable hepatocytes may provide temporary support for patients with acute hepatic failure and save the lives of patients awaiting orthotopic liver transplantation (OLT). In the past few years, we have seen several clinical studies testing the efficacy of BAL devices. These preliminary studies have provided some promising results, although current-generation liver-assist devices have not yet demonstrated sufficient efficacy and reliability for routine use. Some of the issues that the field of BAL development continues to wrestle with are: 1) how to support a large cell mass without substrate limitations so that cells function with maximum efficiency; 2) how to maintain high levels of stable long-term liver-specific function in an artificial (and potentially inhospitable) environment; and 3) how to minimize the priming volume (or dead space) that must be filled by blood or plasma from the patient. It is becoming clearer every day that a more fundamental understanding of the effect of environmental parameters on hepatocellular function, as well as host-BAL interactions, is necessary before the concept of BAL becomes a reality available at reasonable cost. This article describes the tissue-engineering principles and critical technologies that are relevant to the design of BAL devices, and provides future directions for the development of the next generation of BAL support systems.