Feihu Zhao ^a,b, Johanna Melke ^a,b, Damien Lacroix ^c, Keita Ito ^a,b,d, Bert van Rietbergen ^a, Sandra Hofmann ^a,b,e

^a. Orthopaedic Biomechanics Group, Dept. Biomedical Engineering, Eindhoven University of Technology, 5600 MB Eindhoven, The Netherlands

^b. Institute for Complex Molecular Systems (ICMS), Eindhoven University of Technology, 5600 MB Eindhoven, The Netherlands

^c. INSIGNEO Institute for in silico Medicine, Dept. Mechanical Engineering, The University of Sheffield, S1 3JD Sheffield, UK

^d. Dept. Orthopaedics, UMC Utrecht, 3508 GA Utrecht, The Netherlands

^e. Institute for Biomechanics, ETH Zurich, Vladimir-Prelog-Weg 3, HCI E355.1, CH-8093 Zurich, Switzerland

In bone tissue engineering (BTE), mineralisation of extracellular matrix (ECM) can be stimulated using for example a perfusion bioreactor, in which fluid flow is used to apply a shear stress to the cells. Irregular scaffold geometries, however, create an extremely complex mechanical environment (i.e. fluid shear stress). To date, it was not possible to quantitatively determine the influence of mechanical stimulation on mineralised matrix formation within a realistic scaffold geometry. In this study, we seek to quantify the wall shear stress change due to the ECM growth within a silk fibroin scaffold. To achieve this, an adaptive in silico model, which can simulate ECM growth and predict ECM mineralisation within scaffold is developed based on the mechano-regulation theory. The irregular geometry of silk fibroin scaffold was reconstructed from micro-computed tomography images. To compute the physical environment within scaffold (i.e. fluid velocity, pressure, shear stress), a combination of homogenisation technique and multiscale computational fluid dynamics approach was employed due to the complexity in geometry. The results show that a constant applied loading to the perfusion bioreactor (i.e. constant flow rate) is not preferable for ECM mineralisation with the growth of ECM within scaffold. This will inform the biomedical engineers to derive an optimal loading profile for achieving higher amount of mineralised bone tissue in vitro.