Combined in vivo/in silico study of mechanobiological mechanisms during endochondral ossification in bone healing

Mechanobiological theories have been introduced to illustrate the interaction between biology and the local mechanical environment during bone healing. Although several theories have been proposed, a quantitative validation using histomorphometric data is still missing. In this study, in vivo histological data based on an ovine animal experiment was quantified and used to validate bone healing simulations focussing on the endochondral ossification process. The bone formation at different callus regions (periosteal and endosteal bone at the medial and lateral side) was analyzed from in vivo data and quantitatively compared with in silico results. A histomorphometric difference was found in medial and lateral hard callus formation 3 weeks after osteotomy. However, the same amount of new bone was formed on both sides between week 3 and 6. Using a parametric approach, distinct ranges for mechanical strain levels regulating tissue formation were found, for which the in silico prediction agrees with the in vivo endochondral ossification both in pattern and quantity. According to this finding, a strain range of 1 to 8% seems to be conducive for cartilage formation while bone formation may be facilitated by strains up to 4%. This study demonstrates the potential of a thorough validation of in silico results for gaining a better understanding of mechanobiological mechanisms during bone healing.