Transport phenomena in a membrane bioartificial liver

It is well recognized that the fluid-dynamics of membrane bioreactors for cell culture significantly impacts on the design of clinical grafts and implants, and that a well-controlled environment (with respect to mass transfer and reaction kinetics) allows at reproducing all specific functions and bioactive factors that assure viability/regeneration of cells. Here we discuss engineering guidelines, design criteria and optimal operative conditions that enable an efficient mass transport of nutrients and catabolites throughout a bioreactor, including transport through polymeric membranes characterized by different morphological and physic-chemical properties. Mathematical modeling of a bioreactor increases its reproducibility and robustness, and enables the prediction and control of the large number of parameters that mutually influence cells and biomaterials in a increasingly complex tissue-engineered system. In this work, both experimental and computational approaches are presented and discussed: from conventional engineering practices based on Residence Time Distribution (RTD) analysis to the latest progresses in Computational Fluid Dynamics (CFD) tools as related to the challenge to predict oxygen, metabolites and catabolites concentration profiles throughout a variety of high cell-density bio-devices. Success cases related to hepatocytes, chondrocytes, epithelial cells cultured in bioreactors are discussed.