Simulation of oxygen carrier mediated oxygen transport to C3A hepatoma cells housed within a hollow fiber bioreactor

A priori knowledge of the dissolved oxygen (02) concentration profile within a hepatic hollow fiber (HF) bioreactor is important in developing an effective bioartificial liver assist device (BLAD). O-2 provision is limiting within HF bioreactors and we hypothesize that supplementing a hepatic HF bioreactor's circulating media with bovine red blood cells (bRBCs),which function as an O-2 carrier, will improve oxygenation. The dissolved O-2 concentration profile within a single HF (lumen, membrane, and representative extra capillary space (ECS)) was modeled with the finite element method, and compared to experimentally measured data obtained on an actual HF bioreactor with the same dimensions housing C3A hepatoma cells. Our results (experimental and modeling) indicate bRBC supplementation of the circulating media leads to an increase in O-2 consumed by C3A cells. Under certain experimental conditions (PO2,IN=95 mmHg, Q=8.30 mL/min), the addition of bRBCs at 5% of the average in vivo human red blood cell concentration (% hRBC) results in similar to 50% increase in the O-2 consumption rate (OCR). By simply adjusting the operating conditions (PO2,(IN)=25 mmHg, Q=1.77 mL/min) and increasing bRBC concentration to 25% hRBC the OCR increase is similar to 10-fold. However, the improved 02 concentration profile experienced by the C3A cells could not duplicate the full range of in Vivo O-2 tensions (25-70 mmHg) typically experienced within the liver sinusoid with this particular HF bioreactor. Nonetheless, we demonstrate that the O-2 transport model accurately predicts O-2 consumption within a HF bioreactor, thus setting up the modeling framework for improving the design of future hepatic HF bioreactors. (c) 2005 Wiley Periodicals, Inc.