Babalola Omotunde M, Bonassar Lawrence J
Department of Biomedical Engineering, Sibley School of Mechanical and Aerospace Engineering, Cornell University, 151 Weill Hall, Ithaca, NY 14853, USA.
J Biomech Eng. 2009 Jun;131(6):061014. doi: 10.1115/1.3128672.
While mechanical stimulation of cells seeded within scaffolds is widely thought to be beneficial, the amount of benefit observed is highly variable between experimental systems. Although studies have investigated specific experimental loading protocols thought to be advantageous for cartilage growth, less is known about the physical stimuli (e.g., pressures, velocities, and local strains) cells experience during these experiments. This study used results of a literature survey, which looked for patterns in the efficacy of mechanical stimulation of chondrocyte seeded scaffolds, to inform the modeling of spatial patterns of physical stimuli present in mechanically stimulated constructs. The literature survey revealed a large variation in conditions used in mechanical loading studies, with a peak to peak strain of 10% (i.e., the maximum amount of deformation experienced by the scaffold) at 1 Hz on agarose scaffolds being the most frequently studied parameters and scaffold. This loading frequency was then used as the basis for simulation in the finite element analyses. 2D axisymmetric finite element models of 2x4 mm2 scaffolds with 360 modulus/permeability combinations were constructed using COMSOL MULTIPHYSICS software. A time dependent coupled pore pressure/effective stress analysis was used to model fluid/solid interactions in the scaffolds upon loading. Loading was simulated using an impermeable frictionless loader on the top boundary with fluid and solid displacement confined to the radial axis. As expected, all scaffold materials exhibited classic poro-elastic behavior having pressurized cores with low fluid flow and edges with high radial fluid velocities. Under the simulation parameters of this study, PEG scaffolds had the highest pressure and radial fluid velocity but also the lowest shear stress and radial strain. Chitosan and KLD-12 simulated scaffold materials had the lowest radial strains and fluid velocities, with collagen scaffolds having the lowest pressures. Parametric analysis showed maximum peak pressures within the scaffold to be more dependent on scaffold modulus than on permeability and velocities to depend on both scaffold properties similarly. The dependence of radial strain on permeability or modulus was more complex; maximum strains occurred at lower permeabilities and moduli, and the lowest strain occurred at the stiffest most permeable scaffold. Shear stresses within all scaffolds were negligible. These results give insight into the large variations in metabolic response seen in studies involving mechanical stimulation of cell-seeded constructs, where the same loading conditions produce very different results due to the differences in material properties.
虽然普遍认为对接种在支架内的细胞进行机械刺激是有益的，但不同实验系统观察到的益处程度差异很大。尽管已有研究调查了被认为有利于软骨生长的特定实验加载方案，但对于细胞在这些实验中所经历的物理刺激（如压力、速度和局部应变）却知之甚少。本研究利用文献调查结果（该调查寻找了对接种软骨细胞的支架进行机械刺激的效果模式）来指导对机械刺激构建体中存在的物理刺激空间模式进行建模。文献调查显示，机械加载研究中使用的条件差异很大，琼脂糖支架在1 Hz频率下的峰峰值应变10%（即支架经历的最大变形量）是研究最频繁的参数和支架。然后将该加载频率用作有限元分析模拟的基础。使用COMSOL MULTIPHYSICS软件构建了具有360种模量/渗透率组合的2x4 mm2支架的二维轴对称有限元模型。采用与时间相关的耦合孔隙压力/有效应力分析来模拟加载时支架中的流体/固体相互作用。使用不可渗透无摩擦加载器在顶部边界模拟加载，流体和固体位移限制在径向轴上。正如预期的那样，所有支架材料都表现出典型的多孔弹性行为，即具有压力核心，流体流动低，边缘具有高径向流体速度。在本研究的模拟参数下，聚乙二醇（PEG）支架具有最高的压力和径向流体速度，但剪切应力和径向应变最低。壳聚糖和KLD - 12模拟支架材料的径向应变和流体速度最低，胶原蛋白支架的压力最低。参数分析表明，支架内的最大峰值压力更多地取决于支架模量而非渗透率，而速度则同样取决于支架的两种属性。径向应变对渗透率或模量的依赖性更为复杂；最大应变出现在较低的渗透率和模量下，最低应变出现在最硬且渗透率最高的支架中。所有支架内的剪切应力均可忽略不计。这些结果揭示了在涉及对接种细胞的构建体进行机械刺激的研究中所观察到的代谢反应的巨大差异，其中由于材料属性的差异，相同的加载条件会产生非常不同的结果。
