Mixtures of hemoglobin‐based oxygen carriers and perfluorocarbons exhibit a synergistic effect in oxygenating hepatic hollow fiber bioreactors

Hepatic hollow fiber (HF) bioreactors are being developed for use as bioartificial liver assist devices (BLADs). In general, BLADs suffer from O₂ limited transport, which reduces their performance. This modeling study seeks to investigate if O₂ carrying solutions consisting of mixtures of hemoglobin‐based oxygen carriers (HBOCs) and perfluorocarbons (PFCs) can enhance O₂ 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 O₂ in the pseudo‐homogeneous PFC/water phase and oxygenated HBOC, was solved to yield the O₂ concentration field in the three HF 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 O₂ to cultured hepatocytes. Moreover, the in vivo O₂ spectrum in a liver sinusoid can be recapitulated by supplementing the HF bioreactor with a mixture of HBOCs and PFCs at an inlet pO₂ of 80 mmHg. Therefore, we expect that PFC‐based oxygen carriers will be more efficient at transporting O₂ at higher O₂ levels (e.g., at an inlet pO₂ of 760 mmHg, which corresponds to pure O₂ in equilibrium with aqueous cell culture media at 1 atm). Biotechnol. Bioeng. 2010; 105: 534–542. © 2009 Wiley Periodicals, Inc.