Investigating the effect of Lacunocanalicular Network Morphology Alteration Due To Aging on Osteocyte FFSS Using Computational Modeling
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Abstract
Exercise and physical activity exert mechanical loading on the bones, stimulating bone formation. Osteocytes are thought to be the bone cells that sense and respond to mechanical loading and that loading induces bone strains and fluid flow shear stresses (FFSS) on the osteocytes. However, how the complex morphology of the osteocyte lacunocanalicular network affects local stresses and strains experienced by the osteocytes is not fully understood. In this study, we assessed the effect of morphological parameters including canalicular density, lacunocanalicular space thickness, dendrite diameter, number of fluid inlets to the lacuna, and load direction on FFSS and bone strains and how these might change with the microstructural deterioration of the LCN that occurs with aging. Four distinct theoretical models were initially created of osteocytes with either ten or eighteen dendrites using a fluid-structure interaction (FSI) method with idealized geometries. Next, two models of young and aged osteocytes were developed from 3D confocal images after FITC staining of the LCN in the femur of a 5-month-old and 22-month-old C57BL6 mouse. Also, several simulated osteocyte models were developed from confocal images of a 4-month-old C57BL6 mouse using a geometry modification approach to model different LCN morphologies. Shear stresses on osteocyte and dendritic membranes were estimated using a computational fluid dynamics (CFD) approach considering the average surface area and volume of each model. The models predicted higher fluid velocity in the canaliculi versus the lacuna. Comparison of idealized models with one fluid inlet versus five fluid inlets indicated that the average shear stress increased from 0.13 Pa to 0.28 Pa and one-half of the dendrites experienced FFSS greater than 0.8 Pa with four more fluid inlets. The 3D simulations of models based on confocal images of osteocytes indicated that the velocity profile alters in the tortuous canaliculi, near canalicular branches, and canalicular junctions. Our findings indicate not only a higher ratio of canalicular to lacunar surface area in the young osteocyte model than in the aged model but also a greater average FFSS in the young model than the aged model. Consequently, osteocytes experience lower shear stresses on the osteocyte body and dendritic membranes in the aged models. Importantly, the surface area of the young osteocyte model with required shear stress for osteocyte response was 23 times greater than the aged osteocyte. Therefore, aged osteocyte is less possible to detect mechanical strains due to lower dendritic surface area which explains the lower mechanoresponsiveness of osteocytes with aging with the same physiological activity. We also predicted that with increasing canalicular density or lacunocanalicular space thickness, FFSS experienced by osteocytes increases. Both the realistic aged osteocyte model generated from confocal images of an aged mouse and the simulated aged osteocyte model generated from confocal images of a young mouse using the geometry modification technique showed similar FFSS results. This study shows the significance of this technique in computer modeling of osteocytes. Overall, this modeling approach based on accurate osteocyte morphologies, may explain the impaired mechano-responsiveness of the osteocytes with aging and could be a powerful tool to predict the effect of bone diseases on osteocyte mechanoresponsive ness.
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Introduction -- Methods -- Results -- Discussion -- Conclusion and future work
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Ph.D. (Doctor of Philosophy)