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.

中文翻译：

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机械负载骨骼中流体/溶质传输的多尺度3D有限元分析。

骨腔-小管系统（LCS）中的液体，营养物和信号分子的运输对于骨细胞的存活和功能至关重要。我们已经应用了光漂白后的荧光恢复（FRAP）方法来量化LCS中负载诱导的流体和溶质的原位运输，但是由于激光穿透的限制，测量仅限于骨膜下30-50μm的皮质区域。通过这项工作，我们旨在使用基于图像的多尺度有限元分析（FEA）方法扩大对小梁和皮质骨中负载诱导的流体和溶质运输的理解。首先将完整的小鼠胫骨从microCT图像重建为三维（3D）线性弹性FEA模型，并在轴向载荷下计算各个位置的矩阵变形。然后将上述3D模型的一部分导入到双相多孔弹性分析平台（FEBio）中，以预测载荷引起的流体压力场，以及间隙溶质/流体流经皮质和小梁区域的LCS。此外，使用先前开发的小管中Brinkman流动的超微结构模型，可以得出次要流动效应，例如作用于骨细胞（假定为骨骼中的机械传感器）的切应力和/或拖曳力。针对先前获得的应变和在皮质皮层上测量的FRAP传输数据，对FEA模型中假设的材料特性进行了验证。我们的结果证明了这种计算方法在估计LCS中的流体通量以及骨和小梁的任何骨位置的骨细胞的细胞刺激力（剪切力和阻力）时的可行性，从而可以进一步研究骨细胞的活化与骨质疏松的关系。体内功能性骨形成。这项研究提供了一个有前途的平台，揭示了潜在的细胞机制，这些潜在的细胞机制是在治疗骨骼缺陷患者中进行锻炼和进行体育锻炼的合成代谢能力的基础。