Flow rates in perfusion bioreactors to maximise mineralisation in bone tissue engineering in vitro

In bone tissue engineering experiments, fluid-induced shear stress can stimulate cells to produce mineralised extracellular matrix (ECM). The application of shear stress on seeded cells can for example be achieved through bioreactors that perfuse medium through porous scaffolds. The generated mechanical environment (i.e. wall shear stress: WSS) within the scaffolds is complex due to the complexity of scaffold geometry. This complexity has prevented setting an optimal loading (i.e. flow rate) of the bioreactor to achieve an optimal distribution of WSS for stimulating cells to produce mineralised ECM. In this study, a combination of computational fluid dynamics approach with mechano-regulation theory was employed to optimise the external flow rate for a perfusion bioreactor. Such flow rate would maximise the scaffold surface fraction, whose WSS was in the range required for mineralisation. As expected, the optimal flow rate was dependent on the scaffold geometry, in particular on the scaffold porosity. However, it was in a reasonable range of 0.5–5 mL/min (or in terms of fluid velocity: 0.166–1.66 mm/s) for the bioreactor used in our study. It is expected that this approach can lead to the reduction of pilot studies required to find optimal loading conditions as well as to a better insight into the parameters that determine the mineralisation within scaffolds