Loading-induced mass transport in articular cartilage

关节软骨是一种光滑的含水组织，排列在我们关节的骨骼末端。它必须支持大负荷，同时提供一个非常低的摩擦界面，并持续我们的生活。这种组织的损伤或退化导致关节炎，这是一种相对常见但疼痛和衰弱的疾病。软骨中的细胞有助于维持健康的组织，但必须依赖于营养物质和其他重要的信号分子（其作用类似于细胞编程指令）从周围组织的迁移，以支持其活动。此外，需要关节中的一些负荷来刺激这种细胞活性。这项研究计划将调查如何加载和滑动发生在关节有助于迁移的分子进入和通过组织液通过泵送行动。对于本研究，将从牛软骨中获得标本，其表现与人软骨相似。滑动和压缩将被施加到试样表面使用自定义加载机以前在我的实验室开发。同时，样品表面将暴露于大小与营养物和信号分子相似的荧光分子浴。然后，我们将把标本切成薄片，用荧光显微镜观察。荧光强度的变化将用于确定荧光分子通过组织深度的浓度分布。这将使我们能够对迁移进行数学建模，并研究这种迁移如何通过施加在表面的特定负载和滑动来增强。我们还将测量从表面到底部变化的组织成分，并确定这如何影响不同大小分子的迁移。然后，我们将开发结合生物力学和分子迁移特性的计算机模拟（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来研究负载和分子迁移控制的细胞活性，这些细胞活性在更真实的模型中模拟关节，这些关节在日常活动中发生负载和滑动，例如行走和爬楼梯。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变化。我们还将应用这些知识在实验室中开发更好的工程软骨组织，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.