Wahlquist Joseph A, DelRio Frank W, Randolph Mark A, Aziz Aaron H, Heveran Chelsea M, Bryant Stephanie J, Neu Corey P, Ferguson Virginia L
Department of Mechanical Engineering, University of Colorado, Boulder, CO, United States.
Applied Chemicals and Materials Division, Material Measurement Laboratory, National Institute of Standards and Technology, Boulder, CO, United States.
Acta Biomater. 2017 Dec;64:41-49. doi: 10.1016/j.actbio.2017.10.003. Epub 2017 Oct 13.
Osteoarthrosis is a debilitating disease affecting millions, yet engineering materials for cartilage regeneration has proven difficult because of the complex microstructure of this tissue. Articular cartilage, like many biological tissues, produces a time-dependent response to mechanical load that is critical to cell's physiological function in part due to solid and fluid phase interactions and property variations across multiple length scales. Recreating the time-dependent strain and fluid flow may be critical for successfully engineering replacement tissues but thus far has largely been neglected. Here, microindentation is used to accomplish three objectives: (1) quantify a material's time-dependent mechanical response, (2) map material properties at a cellular relevant length scale throughout zonal articular cartilage and (3) elucidate the underlying viscoelastic, poroelastic, and nonlinear poroelastic causes of deformation in articular cartilage. Untreated and trypsin-treated cartilage was sectioned perpendicular to the articular surface and indentation was used to evaluate properties throughout zonal cartilage on the cut surface. The experimental results demonstrated that within all cartilage zones, the mechanical response was well represented by a model assuming nonlinear biphasic behavior and did not follow conventional viscoelastic or linear poroelastic models. Additionally, 10% (w/w) agarose was tested and, as anticipated, behaved as a linear poroelastic material. The approach outlined here provides a method, applicable to many tissues and biomaterials, which reveals and quantifies the underlying causes of time-dependent deformation, elucidates key aspects of material structure and function, and that can be used to provide important inputs for computational models and targets for tissue engineering.
Elucidating the time-dependent mechanical behavior of cartilage, and other biological materials, is critical to adequately recapitulate native mechanosensory cues for cells. We used microindentation to map the time-dependent properties of untreated and trypsin treated cartilage throughout each cartilage zone. Unlike conventional approaches that combine viscoelastic and poroelastic behaviors into a single framework, we deconvoluted the mechanical response into separate contributions to time-dependent behavior. Poroelastic effects in all cartilage zones dominated the time-dependent behavior of articular cartilage, and a model that incorporates tension-compression nonlinearity best represented cartilage mechanical behavior. These results can be used to assess the success of regeneration and repair approaches, as design targets for tissue engineering, and for development of accurate computational models.
骨关节炎是一种影响数百万人的致残性疾病，然而由于这种组织复杂的微观结构，用于软骨再生的工程材料一直难以实现。与许多生物组织一样，关节软骨对机械负荷会产生时间依赖性反应，这对细胞的生理功能至关重要，部分原因是固相和液相相互作用以及多个长度尺度上的特性变化。重现时间依赖性应变和流体流动对于成功构建替代组织可能至关重要，但迄今为止在很大程度上被忽视了。在此，微压痕用于实现三个目标：（1）量化材料的时间依赖性力学响应，（2）在整个带状关节软骨的细胞相关长度尺度上绘制材料特性图，以及（3）阐明关节软骨变形的潜在粘弹性、多孔弹性和非线性多孔弹性原因。将未处理和胰蛋白酶处理的软骨垂直于关节表面切片，并使用压痕评估切片表面整个带状软骨的特性。实验结果表明，在所有软骨区域内，力学响应可以用一个假设非线性双相行为的模型很好地表示，并不遵循传统的粘弹性或线性多孔弹性模型。此外，对10%（w/w）的琼脂糖进行了测试，正如预期的那样，它表现为线性多孔弹性材料。这里概述的方法提供了一种适用于许多组织和生物材料的方法，该方法揭示并量化了时间依赖性变形的潜在原因，阐明了材料结构和功能的关键方面，并且可用于为计算模型提供重要输入以及作为组织工程的目标。
阐明软骨和其他生物材料的时间依赖性力学行为对于充分重现细胞的天然机械感觉线索至关重要。我们使用微压痕来绘制未处理和胰蛋白酶处理的软骨在每个软骨区域的时间依赖性特性图。与将粘弹性和多孔弹性行为结合到单个框架中的传统方法不同，我们将力学响应解卷积为对时间依赖性行为的单独贡献。所有软骨区域的多孔弹性效应主导了关节软骨的时间依赖性行为，并且一个包含拉伸 - 压缩非线性的模型最能代表软骨的力学行为。这些结果可用于评估再生和修复方法的成功与否，作为组织工程的设计目标，以及用于开发精确的计算模型。
