Grant: Discovery Grants Program - Individual

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.