Mapping Shear Properties of Articular Cartilage Using Fast Confocal Microscopy

描述(申请人提供)：关节软骨细胞外基质的高度组织化结构导致组织的复杂力学行为。在骨关节炎等疾病中，这种有组织的结构的破坏会损害组织的功能，导致关节失去活动能力。在组织植入物中重建健康关节软骨的功能异质性的能力限制了替换因关节炎而失去的软骨的努力。开发模拟这种功能异质性的材料的关键第一步是表征微米级组织结构如何影响宏观机械响应。近年来，在表征压缩状态下关节软骨平衡力学响应的空间变化方面取得了长足的进展。这项建议建立在这项工作的基础上，并展示了如何扩展这种测量来解决剪切下关节软骨组织的异质动态响应。此外，共焦显微镜制造方面的最新技术进步使三维材料结构的快速原位成像成为可能。通过将这种成像能力与力测量和图像分析工具相结合，现在可以在局部组织、机械和结构响应与施加的宏观剪应力之间制作三维相关图。所提出的实验将充分利用这些能力来研究施加应变率、应变幅度和组织压缩对宏观和微观水平上的材料响应的影响。通过这些实验获得的软骨剪切特性的详细表征将有助于更彻底地了解正常组织的功能，使疾病能够更有效地诊断和监测，并为替换或再生组织的努力提供基准和设计输入。因此，这些研究对于推进研究人员可用的最先进的方法和技术，以及提供关于这种无处不在的重要组织的特性的有价值的信息都是至关重要的。

DESCRIPTION (provided by applicant): The highly organized structure of the articular cartilage extracellular matrix gives rise to the complex mechanical behavior of the tissue. The destruction of this organized structure in diseases such as osteoarthritis compromises the function of the tissue, leading to loss of mobility in the joint. Efforts to replace cartilage lost to arthritis are limited by the ability to reconstruct the functional heterogeneity of healthy articular cartilage in tissue implants. A critical first step to the development of materials that mimic this functional heterogeneity is the characterization of how the micron scale tissue structure affects the macroscopic mechanical response. Recently, considerable advances have been made towards characterizing spatial variations in the equilibrium mechanical response of articular cartilage under compression. This proposal builds on this work and shows how to extend such measurements to address the heterogeneous dynamic response of articular cartilage tissue under shear. Moreover, recent technological advances in the manufacture of confocal microscopes are allowing for rapid in situ imaging of the three dimensional material structure. By combining this imaging capability with force measurement and image analysis tools it is now possible to make three dimensional correlation maps between the local tissue mechanical and structural responses and the applied macroscopic shear stress. The experiments proposed will take full advantage of these capabilities to investigate the effects of the applied strain rate, strain amplitude, and tissue compression on the material response at the macroscopic and microscopic levels. The detailed characterization of the cartilage shear properties obtained from these experiments will lead to a more thorough understanding of function in normal tissue, enable more effective diagnosis and monitoring of disease, and provide benchmarks and design input for efforts to replace or regenerate tissue. As such, these investigations are critical both for advancing the state of the art methods and technologies available to researchers and providing valuable information on the properties of this ubiquitous and important tissue.