Modelling and Investigating the Interactive Role of Fluid Velocity and Pore Pressure in Load-Induced Osteogenesis

Abstract

Current models propose that osteogenesis occurs in regions of high mechanical stimuli such as strain, fluid velocity, or pore pressure. However, in vivo experiments on mouse tibiae under cantilever loading revealed new bone formation exclusively on the anterolateral side, despite the opposite posteromedial surface experiencing comparable magnitudes of these stimuli. This indicates that individual stimulus magnitude is insufficient and suggests an interactive mechanism among them. To investigate this, a poroelastic finite element model was developed to quantify the combined effects of load-induced fluid velocity and pore pressure. Tensile loading generated negative pore pressure, stretching osteocyte processes, while compressive loading produced positive pore pressure, compressing them. Since fluid flow exerts drag forces that also stretch osteocytes, the combined effect of flow and negative pressure on the tensile side was hypothesized to enhance mechanotransduction and trigger osteogenesis. Four potential stimuli were evaluated: dissipation energy density arising from (i) pore pressure, (ii) fluid velocity, (iii) their non-interactive sum, and (iv) their interaction. Comparison with in vivo data showed that only the interactive dissipation energy density accurately predicted both the spatial pattern and rate of new bone formation under high, low, and rest-inserted loading regimes. These results establish that the interaction between fluid velocity and pore pressure, rather than their independent contributions, governs load-induced osteogenesis. The proposed framework advances the mechanistic understanding of bone adaptation and offers a predictive basis for optimizing mechanical and clinical interventions to promote bone formation and mitigate bone loss.