Multiaxial physiological loading generates complex fluid flow and strain patterns in the osteocyte...

Osteocytes, embedded within the lacunar-canalicular system in bone, play a central role in sensing mechanical stimuli and directing bone adaptation. Fluid-structure interaction (FSI) models have emerged as valuable tools to simulate the mechanical environment surrounding osteocytes, but in silico studies have relied on idealized loading conditions to simplify the complex, multiaxial loading that osteocytes are likely exposed to in vivo. In this study, we model the mechanical environment within the lacunar-canalicular system using multiaxial physiologically relevant loading conditions, by incorporating human tibia strains experimentally measured during walking and running by Lanyon et al. (1975) [1], into 3D osteocyte-scale FSI simulations. We here evaluate how interstitial fluid flow and osteocyte strain patterns generated by physiological loading differ from those obtained using a simplified uniaxial sinusoidal loading. Our findings show that despite similar interstitial fluid velocity magnitude, the spatial flow under multiaxial physiological loading is definitely more complex. Multiaxial physiological loading generates fluid velocities and strains that are highly heterogeneous and shift in direction over time, with dendritic strain exceeding by over an order of magnitude the ones of the cell body. Instead, uniaxial sinusoidal loading produces uniform, periodic flows aligned with the primary loading axis, with minimal strain in dendrites perpendicular to this axis. Notably, multiaxial physiological loading induces localized recirculation zones and broader velocity distributions within canaliculi - with extremely low Reynolds number confirming the laminar flow and excluding true turbulence - that can amplify osteocyte mechanosensitive signals. These are not observed in uniaxial sinusoidal loading. These findings highlight the limitations of uniaxial sinusoidal loading as a model of physiological osteocyte mechanics.