Modeling and investigating the interactive role of fluid velocity and pore pressure within the lacunar-canalicular...

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 subjected to cantilever loading revealed new bone formation exclusively on the anterolateral side, although the opposite posteromedial surface experienced comparable magnitudes of these stimuli. This indicates that individual stimulus magnitude is insufficient and indicate an interactive mechanism. 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 that stretched osteocyte processes, whereas compressive loading produced positive pore pressure that compressed them. Because 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 candidate 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 the average rate of new bone formation per unit bone surface under high, low, and rest-inserted cantilever loading. The model also predicted osteogenesis under axial loading, demonstrating robustness. These findings advance mechanistic understanding by establishing that the interaction between fluid velocity and pore pressure, rather than their independent effects, governs load-induced osteogenesis, and provide a predictive basis for optimizing mechanical and clinical interventions to promote bone formation and mitigate bone loss.