Hemoglobin-Based Oxygen Carrier and Convection Enhanced Oxygen Transport in a Hollow Fiber Bioreactor

A mathematical model was developed to study O-2 transport in a convection enhanced hepatic hollow fiber (HF) bioreactor, with hemoglobin-based O-2 carriers (HBOCs) present in the flowing cell culture media stream of the HF lumen. In this study, four HBOCs were evaluated: PEG-conjugated human hemoglobin (MP4), human hemoglobin (hHb), bovine hemoglobin (BvHb) and polymerized bovine hemoglobin (PolyBvHb). In addition, two types of convective flow in the HF extra capillary space (ECS) were considered in this study. Starling flow naturally occurs when both of the ECS ports are closed. If one of the ECS ports is open, forced convective flow through the ECS will occur due to the imposed pressure difference between the lumen and ECS. This type of flow is referred to as cross-flow in this work, since some of the fluid entering the HF lumen will pass across the HF membrane and exit via the open ECS port. In this work, we can predict the dissolved O-2 concentration profile as well as the O-2 transport flux in an individual HF of the bioreactor by solving the coupled momentum and mass transport equations. Our results show that supplementation of the cell culture media with HBOCs can dramatically enhance O-2 transport to the ECS (containing hepatocytes) and lead to the formation of an in vivo-like O-2 spectrum for the optimal culture of hepatocytes. However, both Starling flow and cross-flow have a very limited effect on O-2 transport in the ECS. Taken together, this work represents a novel predictive tool that can be used to design or analyze HF bioreactors that expose cultured cells to defined overall concentrations and gradients of O-2.