Development of a Hybrid Artificial Liver using a Polyurethane Foam/Hepatocyte-Spheroid Packed-Bed Module

Abstract

Primary dog hepatocytes spontaneously formed spheroids in the pores of polyurethane foam (PUF) within 1–2 days of stationary culture. The spheroids, about 100–150 μm in diameter, partly attached to the surface and immobilized inside these pores. The lidocaine disappearance rate decreased to about 4 μg/105 viable cells/day for 10 days, while in the PUF/spheroid culture the rate was maintained at almost the initial level of 8 μg/105 viable cells/day for 10 days. Then, two scales of PUF packed-bed modules were designed. A small module (PUF volume; 14.5 cm3) was used for in vitro culture to investigate optimum culture conditions, and a large module (PUF volume; 300 cm3) was designed for dog experiments. Hepatocytes inoculated in these modules also formed spheroids and maintained almost the same activity of albumin secretion rate (111 μg/cm3 PUF/day in the small module and 87.7 μg/cm3 PUF/day in the large module). These results indicate that the PUF packed-bed module containing hepatocyte-spheroids is promising as a hybrid artificial liver