Bioreactor device with application as a bioartificial liver

Abstract

A bioreactor apparatus comprising two chambers, a feed and waste chamber and a cell chamber separated by a selectively permeable membrane. Within the cell chamber, a biocompatible three-dimensional matrix entraps animal cells or genetic modifications thereof. Due to the presence of this biocompatible matrix, the cell chamber generally has a gel phase, i.e., the biocompatible matrix and cells, and a liquid phase containing a concentrated solution of the cell product to be harvested. Thus, the bioreactor of this invention uses only two chambers to achieve three distinct zones within the apparatus. A bioartificial liver is based on a bioreactor of the type having two fluid paths separated by a permeable medium. The bioreactor can be of either hollow fiber or flat-bed configuration. In the configuration using hollow fibers, the two fluid paths correspond to the cavity surrounding the hollow fibers (the extracapillary space), and to the lumens of the hollow fibers themselves. Both fluid paths have inlet and outlet ports. Communication between the two fluid paths is across the permeable medium--the hollow fiber material. Hepatocytes are inoculated into the hollow fibers in a solution which quickly forms a highly porous gel. The gel subsequently contracts, leaving an open channel within the hollow fiber adjacent to the gel core entrapped hepatocytes. This channel can be perfused with nutrient media for hepatocytes. The channel can also serve as a waste stream to remove toxins that the hepatocytes have modified to a water soluble form.