Development of a hybrid artificial liver using a polyurethane foam/hepatocyte-spheroid packed-bed module

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 mu m in diameter partly attached to the surface and immobilized inside these pores. The lidocaine disappearance rate decreased to about 4 mu g/10(5) viable cells/day for 10 days, while in the PUF/spheroid culture the rate was maintained at almost the initial level of 8 mu g/10(5) viable cells/day for 10 days. Then, two scales of PUF packed-bed modules were designed. A small module (PUF volume; 14.5 cm(3)) was used for in vitro culture to investigate optimum culture conditions, and a large module (PUF volume; 300 cm(3)) was designed for dog experiments. Hepatocytes inoculated in these modules also formed spheroids and maintained almost the same activity of albumin secretion rate (111 mu g/cm(3) PUF/day in the small module and 87. 7 mu g/cm(3) 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.