Morgan Elise F, Longaker Michael T, Carter Dennis R
Biomechanical Engineering Division, Mechanical Engineering Department, Durand Building, Room 215, Stanford University, Stanford, CA 94305, USA.
Matrix Biol. 2006 Mar;25(2):94-103. doi: 10.1016/j.matbio.2005.10.006. Epub 2005 Dec 5.
Mechanical factors modulate the morphogenesis and regeneration of mesenchymally derived tissues via processes mediated by the extracellular matrix (ECM). In distraction osteogenesis, large volumes of new bone are created through discrete applications of tensile displacement across an osteotomy gap. Although many studies have characterized the matrix, cellular and molecular biology of distraction osteogenesis, little is known about relationships between these biological phenomena and the local physical cues generated by distraction. Accordingly, the goal of this study was to characterize the local physical environment created within the osteotomy gap during long bone distraction osteogenesis. Using a computational approach, we quantified spatial and temporal profiles of three previously identified mechanical stimuli for tissue differentiation-pressure, tensile strain and fluid flow-as well as another candidate stimulus-tissue dilatation (volumetric strain). Whereas pressure and fluid velocity throughout the regenerate decayed to less than 31% of initial values within 20 min following distraction, tissue dilatation increased with time, reaching steady state values as high as 43% strain. This dilatation created large reductions and large gradients in cell and ECM densities. When combined with previous findings regarding the effects of strain and of cell and ECM densities on cell migration, proliferation and differentiation, these results indicate two mechanisms by which tissue dilatation may be a key stimulus for bone regeneration: (1) stretching of cells and (2) altering cell and ECM densities. These results are used to suggest experiments that can provide a more mechanistic understanding of the role of tissue dilatation in bone regeneration.
机械因素通过细胞外基质（ECM）介导的过程调节间充质来源组织的形态发生和再生。在牵张成骨中，通过在截骨间隙上离散施加拉伸位移来生成大量新骨。尽管许多研究已经对牵张成骨的基质、细胞和分子生物学进行了表征，但对于这些生物学现象与牵张产生的局部物理线索之间的关系却知之甚少。因此，本研究的目的是表征长骨牵张成骨过程中截骨间隙内产生的局部物理环境。我们采用计算方法，量化了三种先前确定的用于组织分化的机械刺激——压力、拉伸应变和流体流动——以及另一种候选刺激——组织扩张（体积应变）的空间和时间分布。在牵张后20分钟内，整个再生组织中的压力和流体速度衰减至初始值的31%以下，而组织扩张随时间增加，达到高达43%应变的稳态值。这种扩张导致细胞和ECM密度大幅降低并产生大梯度。当与先前关于应变以及细胞和ECM密度对细胞迁移、增殖和分化影响的研究结果相结合时，这些结果表明组织扩张可能是骨再生关键刺激的两种机制：（1）细胞拉伸和（2）改变细胞和ECM密度。这些结果被用于提出一些实验，这些实验可以提供对组织扩张在骨再生中作用的更具机械性的理解。
