Visual mapping of computational shear stresses implies mechanical control of cell proliferation and differentiation in bone tissue engineering cultures

The advantages of longitudinal monitoring techniques are getting more attention in various tissue engineering approaches. They provide consecutive information about one and the same sample over
time and as such may decrease sample numbers tremendously. These techniques also allow taking the actual environmental status of a tissue into account for predicting future development. Micro-computed
tomography has been previously shown to be suitable to monitor mineralized extracellular matrix deposition in bone tissue engineering cultures. In this study, shear stresses (SS) acting on human mesenchymal stromal cells (hMSC) seeded on silk fibroin scaffolds in a flow perfusion bioreactor were calculated by computational fluid dynamics. Two different flow rates were investigated, mimicking expected loads on cells during early bone repair (0.001 m/s) and during bone remodeling (0.061 m/s), respectively. The threedimensional (3D) distribution of these stresses was then visually mapped to the distribution of the mineralized extracellular matrix deposited by the cells. SS values from 0.55–24 mPa were shown to promote osteogenic differentiation of hMSCs, whereas SS between 0.06 and 0.39 mPa were found to induce cell proliferation. Histological and biochemical analyses have confirmed these findings. In the future, these results may allow predicting the behavior of hMSC in 3D tissue culture. The non-destructive nature of this technique may even allow tight control and adaptation of the mechanical load during culture by taking the present status of the tissue into account.