Fan Lixia, Pei Shaopeng, Lucas Lu X, Wang Liyun
Department of Mechanical Engineering, University of Delaware, Newark, DE, USA; School of Mechanical Engineering, Nanjing University of Science and Technology, Nanjing, China.
Department of Mechanical Engineering, University of Delaware , Newark, DE, USA.
Bone Res. 2016 Sep 27;4:16032. doi: 10.1038/boneres.2016.32. eCollection 2016.
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 , 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 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.
骨陷窝-小管系统（LCS）中液体、营养物质和信号分子的运输对于骨细胞的存活和功能至关重要。我们已应用光漂白后荧光恢复（FRAP）方法来量化LCS中负荷诱导的液体和溶质运输，但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，我们旨在使用基于多尺度图像的有限元分析（FEA）方法，扩大对小梁骨和皮质骨中负荷诱导的液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，并计算轴向加载下不同位置的基质变形。然后将上述3D模型的一部分导入双相多孔弹性分析平台（FEBio），以预测负荷诱导的流体压力场，以及皮质和小梁区域中通过LCS的间质溶质/流体流动。此外，使用先前开发的小管中布林克曼流的超微结构模型，推导了作用于骨细胞（假定为骨中的机械传感器）的剪切应力和/或拖曳力等二次流效应。FEA模型中假设的材料特性根据先前在皮质骨皮质上测量的应变和FRAP运输数据进行了验证。我们的结果证明了这种计算方法在估计LCS中的流体通量以及任何皮质和小梁骨位置的骨细胞的细胞刺激力（剪切力和拖曳力）方面的可行性，从而能够进一步研究骨细胞的激活与功能性骨形成之间的相关性。该研究提供了一个有前景的平台，以揭示运动和体育活动在治疗骨骼缺陷患者中的合成代谢能力背后的潜在细胞机制。
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