Muñoz Asier, De Paolis Annalisa, Cardoso Luis, Carriero Alessandra
Department of Biomedical Engineering, The City College of New York, New York, NY, United States.
Front Bioeng Biotechnol. 2025 Sep 12;13:1639788. doi: 10.3389/fbioe.2025.1639788. eCollection 2025.
Osteocytes play a critical role in bone mechanobiology, sensing and responding to mechanical loading through fluid flow within the lacunar-canalicular network (LCN). Experimental measurements of interstitial fluid flow in bone are difficult due to the embedded nature of osteocytes in the dense mineralized matrix. Therefore, accurate computer simulations of these processes are essential for understanding bone mechanobiology. Two computational approaches have mostly been used to characterize convective interstitial fluid flow in bone: poroelastic finite element (FE) models, which treat bone as a homogenized porous medium, and fluid-structure interaction (FSI) models, which incorporate explicit LCN microarchitecture. However, these approaches have predicted fluid velocities that differ by three to four orders of magnitude. Here, we investigate the reasons for this discrepancy and demonstrate how imposed pressure gradients influence the predicted fluid velocities. Using an FSI model of a single osteocyte embedded in the mineralized matrix, we show that when an imposed pore pressure gradient is smaller than that generated by bone matrix deformation under mechanical loading, the convective fluid velocities in the canaliculi reach ∼100 nm/s and scale with the applied strain. In contrast, applying higher pressure gradients decouples fluid flow from the solid bone matrix deformation, resulting in fluid velocities bigger than 100 μm/s that are insensitive to loading conditions. Future studies investigating the effect of load-induced convection flow on osteocyte mechanobiology should therefore apply small imposed pressure gradients to avoid overestimating interstitial flow and more realistically capture load-induced convective flow.
骨细胞在骨力学生物学中起着关键作用，通过腔隙-小管网络（LCN）内的流体流动来感知并响应机械负荷。由于骨细胞嵌入致密矿化基质中的特性，对骨组织间质液流动进行实验测量十分困难。因此，对这些过程进行精确的计算机模拟对于理解骨力学生物学至关重要。目前主要有两种计算方法用于描述骨组织中的对流性间质液流动：多孔弹性有限元（FE）模型，即将骨视为均匀化的多孔介质；以及流固耦合（FSI）模型，该模型纳入了明确的LCN微观结构。然而，这些方法预测的流体速度相差三到四个数量级。在此，我们探究这种差异的原因，并展示施加的压力梯度如何影响预测的流体速度。通过使用嵌入矿化基质中的单个骨细胞的FSI模型，我们发现，当施加的孔隙压力梯度小于机械负荷下骨基质变形产生的压力梯度时，小管中的对流流体速度达到约100纳米/秒，并随施加的应变而变化。相比之下，施加更高的压力梯度会使流体流动与固体骨基质变形解耦，导致流体速度大于100微米/秒，且对负荷条件不敏感。因此，未来研究负荷诱导的对流流动对骨细胞力学生物学的影响时，应施加较小的外加压力梯度，以避免高估间质液流动，并更真实地捕捉负荷诱导的对流流动。
