Simulation of fracture healing incorporating mechanoregulation of tissue differentiation and dispersal/proliferation of cells

Abstract

Modelling the course of healing of a long bone subjected to loading has been the subject of several investigations. These have succeeded in predicting the differentiation of tissues in the callus in response to a static mechanical load and the diffusion of biological factors. In this paper an approach is presented which includes both mechanoregulation of tissue differentiation and the diffusion and proliferation of cell populations (mesenchymal stem cells, fibroblasts, chondrocytes, and osteoblasts). This is achieved in a three-dimensional poroelastic finite element model which, being poroelastic, can model the effect of the frequency of dynamic loading. Given the number of parameters involved in the simulation, a parameter variation study is reported, and final parameters are selected based on comparison with an in vivo experiment. The model predicts that asymmetric loading creates an asymmetric distribution of tissues in the callus, but only for high bending moments. Furthermore the frequency of loading is predicted to have an effect. In conclusion, a numerical algorithm is presented incorporating both mechanoregulation and evolution of cell populations, and it proves capable of predicting realistic difference in bone healing in a 3D fracture callus.