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.