Bioreactor for a larger scale hepatocyte in vitro perfusion

Abstract

A bioreactor construction for hepatocytes and liver sinusoidal endothelial cells is described. The reactor is based on capillaries for hepatocyte immobilization. Four discrete capillary membrane systems, each serving different purposes, are woven to create a three-dimensional framework for decentralized cell perfusion with low metabolite gradients and decentralized oxygenation and CO2 removal. The biochemical performance of reactors initially seeded with 2.5 x 10(9) hepatocytes were evaluated over 3 weeks. On day 21, pig albumin synthesis was 4.7 mg/day, lidocaine metabolism was 813.7 +/- 23 micrograms/hr, galactose elimination was 210.1 +/- 3 mg/hr, and midazolam metabolism was 37.1 +/- 2 micrograms/hr. The specific construction of the reactor enables scale-up to hybrid liver support systems as extracorporeal bridging devices for liver transplantation.