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.
Highlights
It is well known that bone tissue is capable of adapting its mass and structure in response to mechanical cues.[1]
Quantifying the mechanical stimulation, remains a challenge, because of the complex structure and inhomogeneous material properties of the bone tissue[32] and the different mechanical loading parameters associated with various exercise regimens.[9,10]
One striking feature of the bone tissue is the multiscaled, interconnected pore system housing the cellular components in bone, spanning the central marrow cavity, vascular channels, and the lacunar–canalicular system (LCS).[9]
Summary
It is well known that bone tissue is capable of adapting its mass and structure in response to mechanical cues.[1]. Previous experiments have shown that bone cells were more sensitive to loading-induced fluid flow than matrix strains.[6,7] Recent studies strongly
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