Multiscale Modeling of Regenerated Bone

Bone is a heterogenous, hierarchical biological composite, with varying organization at different length scales. Improving our understanding of how bone regeneration and healing affect this organization and subsequent mechanical performance at different length scales is vital for targeting human health. The mouse P3 digit regeneration process has been valuable in studying fundamental mechanisms underlying bone regeneration and healing and their connections to aging. Regenerative outcomes in this digit bone have been previously quantified using imaging techniques such as micro-computed tomography (µCT) techniques with focus on architectural parameters. However, while imaging has enabled insight into morphology of regenerative bone formation, evaluation of the structural properties and mechanical response of the regenerated bone material has been largely absent. In response, analysis of regenerated bone structural quality and mechanical response is targeted through development of a µCT to finite element (FE) pipeline, where this work details the development of a FE-based model to predict mechanical performance of regenerated bone. Specific aims include 1) building of morphologically accurate 3D FE models of regenerated and uninjured mouse P3 digit bone from µCT images, 2) local property assignment of mechanical properties, and 3) prediction of mechanical performance of regenerated bone and uninjured bone through simulation. Initial results capture the difference in structure and response between uninjured and regenerated bone and effect of structure on damage initiation and propagation, in particular the increase in stress concentrations and flaws in regenerated bone. The expected outcomes of this ongoing work will advance our ability to evaluate and predict the structure and mechanical response of regenerated bone, enable more powerful evaluation of regeneration treatments, and assist in development of next-generation biomimicking healing materials.