Hepatic hollow fiber (HF) bioreactors are being developed for use as bioartificial liver assist devices (BLADs). In general, BLADs suffer from O-2 limited transport, which reduces their performance. This modeling study seeks to investigate if O-2 carrying solutions consisting of mixtures of hemoglobin-based oxygen carriers (HBOCs) and perfluorocarbons (PFCs) can enhance O-2 transport to hepatocytes cultured in the extra capillary space (ECS) of HF bioreactors. We simulated supplementing the circulating cell culture media stream of the HF bioreactor with a mixture containing these two types of oxygen carriers (HBOCs and PFCs). A mathematical model was developed based on the dimensions and physical characteristics of a commercial HF bioreactor. The resulting set of partial differential equations, which describes fluid transport; as well as, mass transport of dissolved O-2 in the pseudo-homogeneous PFC/water phase and oxygenated HBOC, was solved to yield the O-2 concentration field in the three HT domains (lumen, membrane and ECS). Our results show that mixtures of HBOC and PFC display a synergistic effect in oxygenating the ECS, Therefore, the presence of both HBOC and PFC in the circulating cell culture media dramatically improves transport Of O-2 to cultured hepatocytes. Moreover, the in vivo O-2 spectrum in a liver sinusoid can be recapitulated by supplementing the HF bioreactor with a Mixture of HBOCs and PFCs at an inlet pO(2) of 80 mmHg. Therefore, we expect that PFC-based oxygen carriers will be more efficient at transporting O-2 at higher O-2 levels (e.g., at an inlet pO(2) of 760 mmHg, which corresponds to Pure O-2 in equilibrium with aqueous cell Culture media at 1 atm). Biotechnol. Bioeng. 2010;105: 534-542. (C) 2009 Wiley Periodicals, Inc.