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Keywords:

  • hemoglobin-based oxygen carrier;
  • perfluorocarbon;
  • hollow fiber bioreactor;
  • bioartificial liver assist device;
  • oxygen transport;
  • mathematical model

Abstract

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.