A comprehensive computational study modelling the operation of a rotating hollow-fiber bioreactor for artificial liver (BAL) was performed to explore the interactions between the oxygenated culture medium and the cultured hepatocytes. Computational fluid dynamics investigations were carried out using two-dimensional (2D) and 3D time-dependent numerical simulations, integrating calculations of diffusion, convection, and multiphase fluid dynamics. The analysis was aimed at determining the rotational speed value of the chamber to ensure homogenous distribution of the floating microcarrier-attached aggregated cells (μCAACs) and avoid their sedimentation and excessive packing, analyzing oxygen (O2) delivery and cellular O2 consumption as an index of cellular metabolic activity, and analyzing the fluid-induced mechanical stress experienced by cells. According to our results, homogeneous distribution of cells is reached at a rotational speed of 30 rpm; spreading of cellular concentration at around the initial value of 12% was limited (median = 11.97%, 5th percentile = 10.94%, 95th percentile = 13.2%), resulting in uniform suspension of μCAACs, which did not appear to be excessively packed. Mixing within the rotating fluid caused a maximum fluid-induced stress value of 0.05 Pa, which was neither endangering for liver-specific functions of cultured cells, nor causing disruption of the floating aggregates. Moreover, an inlet medium flow rate of 200 mL/m with a partial pressure of oxygen (pO2) value of 160 mmHg was found to guarantee an adequate O2 supply for the hepatocytes (2.7 × 108 hepatocytes are simulated); under such conditions, the minimum pO2 value (23 mmHg) is above the critical threshold value, causing the onset of cellular hypoxia (10 mmHg). We proved that numerical simulation of transport phenomena is a valuable tool for the computer-aided design of BALs, helping overcome the unsolved issues in optimizing the cell-environment conditioning procedure in rotating BALs.
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