Loading-induced mass transport in articular cartilage

关节软骨是一种光滑的水合组织，排列在关节骨骼的末端。它必须支持大载荷，同时提供非常低的摩擦界面，并持续我们的一生。这种组织的损伤或退化导致关节炎，这是一种相对常见但痛苦且使人衰弱的疾病。软骨细胞有助于维持健康的组织，但必须依赖于从周围组织中迁移的营养物质和其他重要的信号分子（就像细胞编程指令一样）来支持它们的活动。此外，在关节中需要一些载荷来刺激这种细胞的活动。该研究项目将研究关节中发生的载荷和滑动如何通过泵送作用促进分子进入和通过组织液的迁移。在本研究中，将从奶牛软骨中获得与人类软骨相似的标本。滑动和压缩将应用于试样表面使用自定义加载机以前在我的实验室开发。同时，样品表面将暴露在荧光分子浴中，荧光分子的大小与营养物质和信号分子相似。然后将标本切成薄片，用荧光显微镜观察。荧光强度的变化将被用来确定通过组织的深度荧光分子的浓度分布。这将使我们能够对迁移进行数学建模，并研究如何通过施加在表面的特定载荷和滑动来增强这种迁移。我们还将测量从表面到底部变化的组织的组成，并确定这如何影响不同大小的分子的迁移。然后，我们将开发结合生物力学和分子迁移特征的计算机模拟（有限元模型），并通过实验结果证实这些模型的预测。这将使我们能够在未来应用这些技术，在更现实的模型中研究负载和分子迁移控制的细胞活动，这些模型模拟在日常活动（如步行和爬楼梯）中发生的负载和滑动的关节。这些未来的研究将帮助我们制定活动指南，以促进健康的软骨，即使组织随着年龄的增长而变化。我们还将在实验室中应用这些知识来开发更好的工程软骨组织，使其能够承受关节中的力和运动。

Articular cartilage is a smooth, hydrated tissue that lines the ends of bones in our joints. It must support large loads while providing a very low friction interface and last for our lifetime. Damage or degeneration of this tissue leads to arthritis, a relatively common yet painful and debilitating disease. Cells in cartilage help maintain healthy tissue but must rely on migration of nutrients and other important signalling molecules (that act like cell programming instructions) from surrounding tissues in order to support their activity. Furthermore, some loading in the joint is required to stimulate this cell activity. This research program will investigate how loading and sliding that occurs in the joint contribute to the migration of molecules into and through the tissue fluid through a pumping action. For this study, specimens will be obtained from cow cartilage which behaves similarly to human cartilage. Sliding and compression will be applied to the specimen surface using a custom loading machine previously developed in my lab. At the same time, the specimen surface will be exposed to a bath of a fluorescent molecule that is similar in size to nutrients and signal molecules. We will then cut the specimens into thin sections and observe them using a fluorescent microscope. Variation of the fluorescent intensity will be used to determine the concentration profile of the fluorescent molecule through the depth of the tissue. This will allow us to mathematically model the migration, and study how this migration is enhanced by the particular load and sliding applied at the surface. We will also measure the composition of the tissue which varies from the surface to the bottom, and determine how this affects migration of molecules of different sizes. We will then develop computer simulations (finite element models) of the combined biomechanical and molecular migration characteristics and confirm the predictions from these models with experimental results. This will allow us to apply the techniques in the future to study loading- and molecular migration-controlled cell activity in more realistic models that simulate articular joints with loading and sliding that occurs during daily activities such as walking and stair climbing. These future studies will help us develop activity guidelines to promote healthy cartilage, even as the tissue changes with age. We will also apply this knowledge to develop better engineered cartilage tissue in the lab that is capable of withstanding the forces and motions in the joint.