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A multiscale 3D finite element analysis of fluid/solute transport in mechanically loaded bone

View Article: PubMed Central - PubMed

ABSTRACT

The transport of fluid, nutrients, and signaling molecules in the bone lacunar–canalicular system (LCS) is critical for osteocyte survival and function. We have applied the fluorescence recovery after photobleaching (FRAP) approach to quantify load-induced fluid and solute transport in the LCS in situ, but the measurements were limited to cortical regions 30–50 μm underneath the periosteum due to the constrains of laser penetration. With this work, we aimed to expand our understanding of load-induced fluid and solute transport in both trabecular and cortical bone using a multiscaled image-based finite element analysis (FEA) approach. An intact murine tibia was first re-constructed from microCT images into a three-dimensional (3D) linear elastic FEA model, and the matrix deformations at various locations were calculated under axial loading. A segment of the above 3D model was then imported to the biphasic poroelasticity analysis platform (FEBio) to predict load-induced fluid pressure fields, and interstitial solute/fluid flows through LCS in both cortical and trabecular regions. Further, secondary flow effects such as the shear stress and/or drag force acting on osteocytes, the presumed mechano-sensors in bone, were derived using the previously developed ultrastructural model of Brinkman flow in the canaliculi. The material properties assumed in the FEA models were validated against previously obtained strain and FRAP transport data measured on the cortical cortex. Our results demonstrated the feasibility of this computational approach in estimating the fluid flux in the LCS and the cellular stimulation forces (shear and drag forces) for osteocytes in any cortical and trabecular bone locations, allowing further studies of how the activation of osteocytes correlates with in vivo functional bone formation. The study provides a promising platform to reveal potential cellular mechanisms underlying the anabolic power of exercises and physical activities in treating patients with skeletal deficiencies.

No MeSH data available.


Confocal imaging of the murine cortical LCS. A stack of LCS images (a) was acquired. Individual lacuna (b) and canaliculi (c) were segmented and pore volumes measured.
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fig3: Confocal imaging of the murine cortical LCS. A stack of LCS images (a) was acquired. Individual lacuna (b) and canaliculi (c) were segmented and pore volumes measured.

Mentions: Extensive LCS pores were labeled with high-intensity green fluorescence in the high-resolution 3D stacks of confocal images (Figure 3a), and the images were thresholded and segmented into lacunae and canaliculi categories (based on size criteria) for calculation of the porosity (Figure 2b and c). The volume fractions of the lacunae and canaliculi were found to be 1.9% and 13.5%, respectively. The total LCS porosity (15.4%) was then used as an input to the segment model. This porosity was also used to scale the tissue-level fluid flow predicted by the segment model to that at the canalicular level in the ultrastructural model.


A multiscale 3D finite element analysis of fluid/solute transport in mechanically loaded bone
Confocal imaging of the murine cortical LCS. A stack of LCS images (a) was acquired. Individual lacuna (b) and canaliculi (c) were segmented and pore volumes measured.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5037578&req=5

fig3: Confocal imaging of the murine cortical LCS. A stack of LCS images (a) was acquired. Individual lacuna (b) and canaliculi (c) were segmented and pore volumes measured.
Mentions: Extensive LCS pores were labeled with high-intensity green fluorescence in the high-resolution 3D stacks of confocal images (Figure 3a), and the images were thresholded and segmented into lacunae and canaliculi categories (based on size criteria) for calculation of the porosity (Figure 2b and c). The volume fractions of the lacunae and canaliculi were found to be 1.9% and 13.5%, respectively. The total LCS porosity (15.4%) was then used as an input to the segment model. This porosity was also used to scale the tissue-level fluid flow predicted by the segment model to that at the canalicular level in the ultrastructural model.

View Article: PubMed Central - PubMed

ABSTRACT

The transport of fluid, nutrients, and signaling molecules in the bone lacunar–canalicular system (LCS) is critical for osteocyte survival and function. We have applied the fluorescence recovery after photobleaching (FRAP) approach to quantify load-induced fluid and solute transport in the LCS in situ, but the measurements were limited to cortical regions 30–50 μm underneath the periosteum due to the constrains of laser penetration. With this work, we aimed to expand our understanding of load-induced fluid and solute transport in both trabecular and cortical bone using a multiscaled image-based finite element analysis (FEA) approach. An intact murine tibia was first re-constructed from microCT images into a three-dimensional (3D) linear elastic FEA model, and the matrix deformations at various locations were calculated under axial loading. A segment of the above 3D model was then imported to the biphasic poroelasticity analysis platform (FEBio) to predict load-induced fluid pressure fields, and interstitial solute/fluid flows through LCS in both cortical and trabecular regions. Further, secondary flow effects such as the shear stress and/or drag force acting on osteocytes, the presumed mechano-sensors in bone, were derived using the previously developed ultrastructural model of Brinkman flow in the canaliculi. The material properties assumed in the FEA models were validated against previously obtained strain and FRAP transport data measured on the cortical cortex. Our results demonstrated the feasibility of this computational approach in estimating the fluid flux in the LCS and the cellular stimulation forces (shear and drag forces) for osteocytes in any cortical and trabecular bone locations, allowing further studies of how the activation of osteocytes correlates with in vivo functional bone formation. The study provides a promising platform to reveal potential cellular mechanisms underlying the anabolic power of exercises and physical activities in treating patients with skeletal deficiencies.

No MeSH data available.