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 poly urethane foam (PUF) within 1-2 days of stationary culture. :The spheroids, about 100-150 mu m in diameter partly attached to the surface and immobiliz ed inside these pores. The lidocaine disappearance rate decreased to about 4 mu g/10(5) viable cel ls/day for 10 days, while in the PUF/spheroid culture the rate was maintain ed 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 optim um culture conditions, and a large module (PUF volume; 300 cm(3)) was desig ned for dog experiments. Hepatocytes inoculated in these modules also forme d spheroids and maintained almost the same activity of albumin secretion ra te (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 modul e containing hepatocyte-spheroids is promising as a hybrid artificial liver .