Fluid flow-induced cell stimulation in bone tissue engineering changes due to interstitial tissue formation in vitro

In tissue engineering experiments in vitro, bioreactors have been used for applying wall shear stress (WSS) on cells to regulate cellular activities. To determine the loading conditions within bioreactors and to design tissue engineering products, in silico models are used. Previous in silico studies in bone tissue engineering (BTE) focused on quantifying the WSS on cells and the influence on appositional tissue growth. However, many BTE experiments also show interstitial tissue formation (i.e., tissue infiltrated in the pores rather than growing on the struts - appositional growth), which has not been considered in previous in silico studies. We hereby used a multiscale fluid-solid interaction model to quantify the WSS and mechanical strain on cells with interstitial tissue formation, taken from a reported BTE experiment. The WSS showed a high variation among different interstitial tissue morphologies. This is different to the situation under appositional tissue growth. It is found that a 35% filling of the pores results (by mineralised bone tissue) when the average WSS increases from 1.530 (day 0) to 5.735 mPa (day 28). Furthermore, the mechanical strain on cells caused by the fluid flow was extremely low (at the level of 10^-14 -10^-15 ), comparing to the threshold in a previous mechanobiological theory of osteogenesis (eg, 10^-2 ). The output from this study offers a significant insight of the WSS changes during interstitial tissue growth under a constant perfusion flow rate in a BTE experiment. It has paved the way for optimising the local micro-fluidic environment for interstitial tissue mineralisation.