Implantable Hepatocyte Culture on 3-D Biopolymers

Acute and chronic liver dysfunction cause approximately 30,000 deaths yearly. Limited supplies of donor organs allow only about 3000 transplants per year. Techniques for temporary liver function replacement (partial transplantation, extracorporeal methods including cross circulation, exchange transfusion, perfusion) are minimally successful. A promising approach is the bioartificial liver (BAL) which can maintain differentiated functions of large numbers of hepatocytes for extended periods. Many investigators have observed that electrical stimulation, either by application of small direct currents or by use of piezoelectric materials, enhances tissue regeneration, e.g., ossification of bone, spinal fusions, and peripheral nerve regeneration. Our concept of an implantable BAL is an open celled polymeric foam scaffold prepared by lyophilization that can support hepatocyte attachment and through which nutrients and waste may be transported. Foams are rendered piezoelectric by high intensity corona poling, a non-discharge process that orients molecular dipoles thus creating electrical polarization parallel to the intense electric field of the corona. Polymers will be selected from the absorbable, biocompatible poly(lactide-co-glycolide)'s. Thus as hepatocytes develop within the foam scaffold and take over liver functions, the scaffold is slowly absorbed. We have shown that mouse neuroblastoma cells cultured on piezoelectric poly(L-lactide), films show statistically greater numbers of cells with neurites, as well as number of neurites per cell than do controls. By analogy, we speculate that foams rendered piezoelectric will be better able to support hepatocyte function and viability than nonpiezoelectric foams. PROPOSED COMMERCIAL APPLICATIONS: This work is significant as a step toward developing an implantable degradable 3-D tissue engineering device for patients suffering acute liver failure. It will replace liver function as liver regeneration occurs.