After fracture, mesenchymal stem cells (MSCs) and growth factors migrate into the fracture callus to exert their biological actions. Previous studies have indicated that dynamic loading induced tissue deformation and interstitial fluid flow could produce a biomechanical environment which significantly affects the healing outcomes. However, the fundamental relationship between the various loading regimes and different healing outcomes has not still been fully understood. In this study, we present an integrated computational model to investigate the effect of dynamic loading on early stage of bone fracture healing. The model takes into account cell and growth factor transport under dynamic loading, and mechanical stimuli mediated MSC differentiation and tissue production. The developed model was firstly validated by the available experimental data, and then implemented to identify the loading regimes that produce the optimal healing outcomes. Our results demonstrated that dynamic loading enhances MSC and growth factor transport in a spatially dependent manner. For example, compared to free diffusion, dynamic loading could significantly increase MSCs concentration in endosteal zone; and chondrogenic growth factors in both cortical and periosteal zones in callus. Furthermore, there could be an optimal dynamic loading regime (e.g. 10% strain at 1 Hz) which could potentially significant enhance endochondral ossification.
Keywords: Bone fracture healing; Chondrogenic growth factors; Dynamic loading; Mesenchymal stem cells; Osteogenic growth factors; Solute transport.