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

Abstract

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 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 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).