A mathematical model describing O-2 transport in a hepatic hollow fiber (HF) bioreactor supplemented with perfluorocarbons (PFCs) in the circulating cell culture media was developed to explore the potential of PFCs in properly oxygenating a bioartificial liver assist device (BLAD). The 2-dimensional model is based on the geometry of a commercial HF bioreactor operated under steady-state conditions. The O-2 transport model considers fluid motion of a homogeneous mixture of cell culture media and PFCs, and mass transport of dissolved O-2 in a single HF. Each HF consists of three distinct regions: (1) the lumen (conducts the homogeneous mixture of cell culture media and PFCs), (2) the membrane (physically, separates the lumen from the extracapillary space (ECS), and (3) the ECS (hepatic cells reside in this compartment). In a single HF, dissolved O-2 is predominantly transported in the lumen via convection in the axial direction and via diffusion in the radial direction through the membrane and ECS. The resulting transport equations are solved using the finite element method. The calculated O-2 transfer flux showed that supplementation of the cell culture media with PFCs can significantly enhance O-2 transport to the ECS of the HF when compared with a control with to PFC supplementation. Moreover, the O-2 distribution and subsequent analysis of ECS zonation demonstrate that limited in vivo-like O-2 gradients can be recapitulated with proper selection of the operational settings of the HF bioreactor. Taken together, this model can also be used to optimize the operating conditions for future BLAD development that aim to fully recapitulate the liver's varied functions. (c) 2009 American Institute of Chemical Engineers Biotechnol. Prog., 25: 1317-1321, 2009