Validation of a novel 3D flow model for the optimization of construct perfusion in radial-flow packed-bed bioreactors (rPBBs) for long-bone tissue engineering

Osteogenic cell culture in three-dimensional (3D) hollow cylindrical porous scaffolds in radial-flow packed-bed bioreactors (rPBBs) may overcome the transport limitations of static and axial perfusion bioreactors in the engineering of long-bone substitutes. Flow models of rPBBs help optimize radial flux distribution of medium and tissue maturation in vitro. Only a 2D model is available for steady flow transport in rPBBs with axisymmetric inlet and outlet accounting for the fluid dynamics of void spaces, assessed against literature information. Here, a novel 3D model is proposed for steady flow transport in the three compartments of rPBBs with a more practical lateral outlet. A 3D model of transient tracer transport was developed based on the flow model to predict bioreactor residence time distribution (RTD). Model-predicted flow patterns were validated in terms of RTD against tracer experiments performed with bioreactor prototypes equipped with commercial scaffolds for bone tissue engineering. Bioreactors were challenged with a step change in entering tracer concentration in an optimized set-up under conditions promoting uniform radial flux distribution and typical shunt flows. Model-predicted RTDs agreed well with those experimentally determined. In conclusion, tracer experiments validate the use of the 3D flow model for optimizing construct perfusion in rPBBs to engineer long-bone substitutes.