BONE HEALING IN MICE: DOES IT FOLLOW GENERIC MECHANO-REGULATION RULES?

Abstract

Mechanical signals are known to influence bone healing progression. Previous studies have postulated inter-species differences in the mechanical regulation of the bone healing process. The aim of this study is to investigate whether mechanical “rules” explaining tissue formation patterns during bone healing in rat can be translated to a mouse model of bone regeneration. We have used an established mechano-biological computer model that uses finite element techniques to determine the mechanical conditions within the healing region and an agent-based approach to simulate cellular activity. The computer model is set up to simulate the course of bone healing in a femoral osteotomy model stabilized with an external fixator. Computer model predictions are compared to corresponding histological data. Generic mechano-regulation “rules” able to explain bone healing progression in the rat are not able to describe tissue formation over the course of healing in the mouse. According to the differentiation theory proposed by Prendergast, mechanical stimuli within the healing region immediately post-surgery are determined to be favorable for cartilage and fibrous tissue formation. In contrast, in vivo histological data showed initial intramembraneous bone formation at the periosteal side. These results suggest that in mice, bone does not require as much stability as is required in rat to reach timely healing. This finding emphasizes the need to further investigate the species-specific mechano-biological regulation of bone regeneration.