Beneficial effects of moderate, early loading and adverse effects of delayed or excessive loading on bone healing.

Fracture healing involves the differentiation and proliferation of cells in the callus and the synthesis and degradation of connective, cartilage and bone tissue. These processes are initiated and tightly regulated by growth factors and by the mechanical environment in the callus. In this work we incorporated the effects of mechanical stimulation on cell differentiation and ossification into a previously developed temporal-spatial model of growth factor mediated fracture healing. In particular, the stimulatory and inhibitory effects of dilatational and deviatoric strains were modeled. This predictive model was then calibrated and validated using well-defined in vivo experiments from the literature. As in the experiments, the results of the model demonstrated the beneficial and adverse effects of moderate and excessive loading, respectively, as well as the negative effects of delaying mechanical stimulation of rigidly fixed calluses. In addition, the model examined loading conditions and time points beyond those used in the experiments, providing a more complete and mechanistic characterization of the effects of loading in the biological tissue response associated with fracture healing.