A 3D in Silico Multi-Tissue Evolution Model Highlights the Relevance of Local Strain Accumulation in Bone Fracture Remodeling

Front Bioeng Biotechnol. 2022 Mar 31;10:835094. doi: 10.3389/fbioe.2022.835094. eCollection 2022.

Abstract

Since 5-10% of all bone fractures result in non-healing situations, a thorough understanding of the various bone fracture healing phases is necessary to propose adequate therapeutic strategies. In silico models have greatly contributed to the understanding of the influence of mechanics on tissue formation and resorption during the soft and hard callus phases. However, the late-stage remodeling phase has not been investigated from a mechanobiological viewpoint so far. Here, we propose an in silico multi-tissue evolution model based on mechanical strain accumulation to investigate the mechanobiological regulation of bone remodeling during the late phase of healing. Computer model predictions are compared to histological data of two different pre-clinical studies of bone healing. The model predicted the bone marrow cavity re-opening and the resorption of the external callus. Our results suggest that the local strain accumulation can explain the fracture remodeling process and that this mechanobiological response is conserved among different mammal species. Our study paves the way for further understanding of non-healing situations that could help adapting therapeutic strategies to foster bone healing.

Keywords: bone fracture remodeling; in silico modeling; in vivo validation; mechanobiology; multi-tissue evolution.