Multiscale Fluid Structure Interaction Modelling to Determine the Mechanical Stimulation of Bone Cells in a Tissue Engineered Scaffold

Introduction: Although bone tissue engineering and regenerative medicine are promising strategies for reconstructing bone defects, existing tissue approaches have not been able to regenerate tissue in vitro that can be used clinically to replace degenerated bone, support loading or enhance the growth and differentiation of new bone tissue in vivo. Recent studies have shown that mechanical stimulation enhances bone tissue regeneration in vitro to a certain extent [1]. In particular, it has been shown that osteogenic differentiation, as indicated by ALP, COX2 and PGE2 expressions, is enhanced when bone cells seeded on biomaterial scaffolds are exposed to fluid flow perfusion [2][3]. Computational fluid dynamics (CFD) models have characterised fluid flow within scaffolds and have estimated that a wall shear stress (WSS) lower than 10mPa on the scaffold surfaces was favourable for bone cell differentiation [4], while WSS around 50mPa correlated to the highest bone cell viability and proliferation capacity within a cell-seeded scaffold. However, due to the complex multiscale and multiphysics nature of the cellscaffold-fluid environment, the precise nature of mechanical stimulation being applied at a cellular level remains unclear. Fluidstructure interaction (FSI) models have been applied to predict the cellular deformation within tissue engineered scaffolds under flow perfusion in vitro and have highlighted that the nature of cell-scaffold attachment plays an important role local cell stimulation [6