Comparison between a non-linear and linearized three-compartment model of a bioreactor for hepatocyte culturing

Bioreactor solutions are being increasingly explored as alternatives to surgery treatments of severe hepatic failures. However, complications related to hepatocyte culturing requirements in vitro renders design, operation and optimization of proposed bioreactor solution extremely hard, with stable and durable cultivation of viable and functional cells hardly exceeding ten days. Several factors may limit the survival of hepatocyte cultures in artificial environment including nutrient transport, oxygen diffusion as well as removal of catabolites, but also provision for anchorage support and very limited flow shear stress. In the present work, two versions of a simplified dynamic model of a crossed-hollow-fiber membrane bioreactor are discussed and compared. A linear and non-linear, input-output process models were developed fundamentally, i.e. starting from the equations governing flow, mass transfer, permeation, (bio)chemical reactions, in dynamic conditions.