A novel bioreactor with glass bead matrix (GBM) has been developed at Monsanto and Washington University, in which porcine hepatocytes aggregate into the interstices of the beads, leaving pathways for passage of plasma directly over the cells (as in the native liver). Versus bioreactors with cells placed on the opposite side of membranes from plasma, the GBM has: higher loading capacity, more normal intercellular connections within the aggregates, better mass transfer of chemicals to and from plasma, and chemical function for weeks rather than hours (during albumin solution perfusion). In Phase I, we will determine whether the GBM functions for long periods during xenogenic plasma perfusion and whether there is damage from cytotoxic antibodies. These studies will determine whether the GBM can be used with a simple plasma perfusion circuit or whether a more complex system must be created to immune-isolate the GBM and perfuse it with a serum filtrate containing albumin but no antibodies. The GBM will eventually be used in conjunction with the BioLogic detoxifier system which will remove hepatic failure toxins from the plasma of patients with hepatic failure concomitant with chemical and synthetic function of the GBM. PROPOSED COMMERCIAL APPLICATION Worldwide, over 2 billion people are infected with hepatitis viruses and 10 percent of these patients have chronic liver insufficiency. When complications such as GI bleeding or infection result in acute hepatic failure and coma, an effective and relatively inexpensive liver support device is needed, to support the patients until the complications can be corrected; the patient can then return to their usual health. The market for such a device is much larger than for devices treating kidney failure
Thesaurus Terms:biomedical equipment development, bioreactor, glass, liver cell, plasma antigen antibody reaction, blood treatment, clinical biomedical equipment, extracorporeal circulation, perfusion animal tissue, immature animal, laboratory rat, mature animal, swine
