OMIBONE: Omics-driven computer model of bone regeneration for personalized treatment

Abstract

Treatment of bone fractures are standardized according to the AO classification, which mainly refers to the mechanical stabilization required in a given situation but neglect individual differences due to patient's healing potential or accompanying diseases. Specially in elderly or immune-compromised patients, the complexity of individual constrains on a biological as well as mechanical level are hard to account for. Here, we introduce a novel framework that allows to predict bone regeneration outcome using combined proteomic and mechanical analyses in a computer model. The framework uses Ingenuity Pathway Analysis (IPA) software to link protein changes to alterations in biological processes and integrates these in an Agent-Based Model (ABM) of bone regeneration. This combined framework allows to predict bone formation and the potential of an individual to heal a given fracture setting. The performance of the framework was evaluated by replicating the experimental setup of a mouse femur fracture stabilized with an intramedullary pin. The model was informed by serum derived proteomics data. The tissue formation patterns were compared against experimental data based on x-ray and histology images. The results indicate the framework potential in predicting an individual's bone formation potential and hold promise as a concept to enable personalized bone healing predictions for a chosen fracture fixation.