Development of a scalable throughput Drug hepatotoxicity testing platform based on microfabricated galactosylated silicon nitride membranes

Abstract

Primary hepatocytes are one of the vital components in bioartificial liver assisted devices and drug metabolism/hepatotoxicity study. The major problem of primary hepatocytes is that they loss their hepatic functions quickly in vitro. Many in vitro culture models have been established to help to maintain functional maintenance of primary hepatocytes, among them, collagen gel sandwich culture and bioreactor-based perfusion culture have been attracting interests because of bio-mimic environment provided. However, further applications of sandwich and perfusion are limited by their own disadvantages. In this project, we developed a scalable throughput sandwich perfusion culture system with controllable mass transport and in vivo-like environments based on microfabricated galactosylated porous silicon nitride membrane and 96-well bioreactor. Primary hepatocytes in this sandwich perfusion culture system exhibited long-term maintenance of hepatic functions. Drug-induced hepatotoxicity study by using several model drugs demonstrated that primary hepatocytes in this scalable throughput sandwich perfusion culture system obtained higher drug sensitivity long-term drug testing capability.