Numerical model of fluid flow and oxygen transport in a radial-flow microchannel containing hepatocytes

The incorporation of monolayers of cultured hepatocytes into an extracorpor eal perfusion system has become a promising approach for the development of a temporary bioartificial liver (BAL) support system. In this paper we pre sent a numerical investigation of the oxygen tension, shear stress, and pre ssure drop in a bioreactor for a BAL composed of plasma-perfused chambers c ontaining monolayers of porcine hepatocytes. The chambers consist of microf abricated parallel disks with center-to-edge radial flow. The oxygen uptake rate (OUR), measured in vitro for porcine hepatocytes, was curve-fitted us ing Michaelis-Menten kinetics for simulation of the oxygen concentration pr ofile. The effect of different parameters that may influence the oxygen tra nsport inside the chambers, such as the plasma flow rate, the chamber heigh t, the initial oxygen tension in the perfused plasma, the OUR, and K-m was investigated. We found that both the plasma flow rare and the initial oxyge n tension may have an important effect upon oxygen transport. Increasing th e flow rate and/or the inlet oxygen tension resulted in improved oxygen tra nsport to cells in the radial-flow microchannels, and allowed significantly greater diameter reactor without oxygen limitation to the hepatocytes. In the range investigated in this paper (10 mu m < H < 100 mu m), and for a co nstant plasma flow rate, the chamber height, H, had a negligible effect on the oxygen transport to hepatocytes. On the contrary, it strongly affected the mechanical stress on the cells that is also crucial for the successful design of the BAL reactors. A twofold decrease in chamber height from 50 to 25 mu m produced approximately a fivefold increase in maximal shear stress at the inlet of the reactor from 2 to 10 dyn/cm(2). Further decrease in ch amber height resulted in shear stress values that are physiologically unrea listic. Therefore, the channel height needs to be carefully chosen in a BAL design to avoid deleterious hydrodynamic effects an hepatocytes.