Biomechanics Research Centre (BMEC), Mechanical and Biomedical Engineering, College of Engineering and Informatics, National University of Ireland, Galway, Ireland.
Biomech Model Mechanobiol. 2014 Jan;13(1):85-97. doi: 10.1007/s10237-013-0487-y. Epub 2013 Apr 9.
Osteocytes are believed to be the primary sensor of mechanical stimuli in bone, which orchestrate osteoblasts and osteoclasts to adapt bone structure and composition to meet physiological loading demands. Experimental studies to quantify the mechanical environment surrounding bone cells are challenging, and as such, computational and theoretical approaches have modelled either the solid or fluid environment of osteocytes to predict how these cells are stimulated in vivo. Osteocytes are an elastic cellular structure that deforms in response to the external fluid flow imposed by mechanical loading. This represents a most challenging multi-physics problem in which fluid and solid domains interact, and as such, no previous study has accounted for this complex behaviour. The objective of this study is to employ fluid-structure interaction (FSI) modelling to investigate the complex mechanical environment of osteocytes in vivo. Fluorescent staining of osteocytes was performed in order to visualise their native environment and develop geometrically accurate models of the osteocyte in vivo. By simulating loading levels representative of vigorous physiological activity ([Formula: see text] compression and 300 Pa pressure gradient), we predict average interstitial fluid velocities [Formula: see text] and average maximum shear stresses [Formula: see text] surrounding osteocytes in vivo. Interestingly, these values occur in the canaliculi around the osteocyte cell processes and are within the range of stimuli known to stimulate osteogenic responses by osteoblastic cells in vitro. Significantly our results suggest that the greatest mechanical stimulation of the osteocyte occurs in the cell processes, which, cell culture studies have indicated, is the most mechanosensitive area of the cell. These are the first computational FSI models to simulate the complex multi-physics mechanical environment of osteocyte in vivo and provide a deeper understanding of bone mechanobiology.
骨细胞被认为是骨骼机械刺激的主要传感器,它协调成骨细胞和破骨细胞,使骨结构和组成适应生理负荷需求。量化骨细胞周围力学环境的实验研究具有挑战性,因此,计算和理论方法分别对骨细胞的固体或流体环境进行建模,以预测这些细胞在体内是如何受到刺激的。骨细胞是一种弹性细胞结构,会对外力加载所产生的外部流体流动产生变形。这代表了一个极具挑战性的多物理问题,其中流体和固体域相互作用,因此,以前没有研究考虑到这种复杂的行为。本研究的目的是采用流固耦合(FSI)建模来研究体内骨细胞的复杂力学环境。通过对骨细胞进行荧光染色,以可视化其天然环境,并对体内骨细胞进行几何精确建模。通过模拟代表剧烈生理活动的载荷水平([Formula: see text]压缩和 300 Pa 压力梯度),我们预测了体内骨细胞周围的平均间质流体速度[Formula: see text]和平均最大剪切应力[Formula: see text]。有趣的是,这些值出现在骨细胞细胞过程周围的小管中,并且处于已知刺激体外成骨细胞产生成骨反应的刺激范围内。值得注意的是,我们的结果表明,骨细胞受到的最大机械刺激发生在细胞过程中,细胞培养研究表明,这是细胞最敏感的机械区域。这些是首次模拟体内骨细胞复杂多物理力学环境的计算 FSI 模型,为骨力学生物学提供了更深入的理解。