Isn't It Swell? [electronic resource] : the effect of osmotic swelling on articular cartilage and meniscal fibrocartilage mechanics and diagnostic approaches

Osteoarthritis (OA) is the most common form of arthritis in adults, affecting over 27 million people in the United States alone in one or more of its most common forms: knees, hips, and hand. OA is characterized by the deterioration of joint tissues, such as articular cartilage and the menisci in the knee, as well as the presence of osteophytes. One of the main roles of articular cartilage and meniscus is to assist with the distribution of loads across the knee joint and provide stability and lubrication. The ability of both cartilage and meniscus to sustain compressive loads comes from an osmotic swelling stress resulting from electrochemical interactions between the ionic interstitial fluid and the net negative matrix fixed charge density. Changes in tissue sulfated-glycosaminoglycan (sGAG) content, such as those that occur with degenerative joint disease, alter such contributions, as do changes to the osmotic environment such as those induced by intraarticular contrast agents for clinical imaging. The first half of this thesis explores the effect of sGAG concentration on the osmotic swelling state of cartilage and meniscus explants. Bovine tissue specimens were subjected to confined compression testing as their osmotic environment was systematically altered to quantify the transient response to these changes. Atomic Force Microscopy (AFM) was then used to visualize the effect that these changes to the osmotic environment have on the structure of the collagen network of cartilage and meniscus. The second half of this thesis focused on the application of these principles in a more clinically relevant context. Quantitative Magnetic Resonance Imaging (qMRI) techniques were used to detect changes in the osmotic swelling state of cartilage and meniscus explants. Finally, the transient effects on cartilage and meniscus mechanics of Omnipaque -- a low-osmolar iodinated contrast agent currently used for Computed Tomography (CT) arthrography -- were examined to provide insight into potential clinical implications of altered osmotic interactions. Results from the transient swelling response study suggest that the role of sGAG in maintaining the structural integrity of cartilage and meniscus is as important for tissues with low sGAG concentration as it is for tissues with high sGAG concentrations. AFM results indicate that changes to the collagen network occur with alterations to the osmotic environment, particularly for the meniscus tissue specimens. Alterations to the swelling state in meniscus tissue explants were partially detected using qMRI, in particular, by measuring changes in the value of their T2* relaxation times. This finding is important as it elucidates how specific water content changes, while keeping other tissue constituents constant, affect a key qMRI metric used to assess cartilage and meniscus integrity. Lastly, results from the Omnipaque study show that exposure to iodinated contrast agents results in long-term swelling of the articular cartilage and deswelling of the meniscus that is not completely recoverable after removal of the contrast agents in an explant model. These results suggest that exposure to iodinated contrast agents might compromise the mechanical integrity of cartilage and meniscus and leave both of these tissues (and potentially other tissues exposed to the contrast agents upon injection) susceptible to surface damage.

Keywords: Mechanical Engineering.
Advisor: Levenston Marc Elliot primary advisor. Thesis advisor
Chaudhuri Ovijit advisor. Thesis advisor
Gold Garry E.