BME PhD Candidate, Margot S. Farnham, will be defending her dissertation.
TITLE:
Redefining Articular Cartilage Lubrication: The Role of Hydration Recovery on Tissue Function in Health and Injury
When: Friday March 26 @ 9:30 AM EST
Where: Zoom Meeting: https://udel.zoom.us/j/95172909309 Password: mfarnham
Committee Chair: Christopher Price, PhD
Committee: David L. Burris, PhD., Kyla F. Ortved, PhD., Sarah I. Rooney, PhD.
ABSTRACT:
Intact articular cartilage is crucial to joint health and function: it provides the load bearing and low friction surface necessary for joint articulation. Healthy articular cartilage is particularly resilient, retaining exceptional mechanical functionality throughout millions of reciprocation cycles every year and across many decades of use, despite being avascular and having poor regenerative capacity. Although cartilage has been studied for more than half a century, neither its lubrication nor resiliency is fully understood. The purpose of this dissertation was to identify contributions from various sliding and environmental inputs to the behavior, lubricity, and tribomechanics of articular cartilage to add to the development of a more holistic lubrication structure that explains how cartilage functions on the benchtop and in the joint.
To accomplish this, a novel benchtop testing approach was utilized: the convergent stationary contact area (cSCA) configuration. The cSCA is unique in that it explicitly attempts to preserve and recover crucial hydration, and thus lubrication, properties of articular cartilage that have been found to be present in the joint, unlike much of the previous work that has utilized configurations that explicitly limit/inhibit specific physiological contributors to lubrication. This configuration was first characterized to demonstrate its unique appropriateness for performing repeated tribological characterization tests on articular cartilage explants (Aim 1). Then, the acute effects of clinically relevant injuries on tribological rehydration and cartilage lubrication were identified (Aim 2) under the same sliding conditions that were characterized in Aim 1. We found that injuries causing damage through the full thickness of cartilage (fissures and defects) acutely reduce cartilage’s ability to rehydrate and maintain low frictions, while injuries causing more surface-limited damage (impacts) do not acutely influence cartilage’s tribological function. These results suggest that these injuries precipitate tissue dysfunction through more complex cell-mediated mechanobiological processes, as opposed to primarily mechanically driven mechanisms like the full-thickness injuries.
Next, we utilized different putative lubricants as bathing solutions during cSCA tests to identify how these solutions alter the ability of sliding to drive tribological rehydration (Aim 3). Additionally, the functional viscosity of in vivo lubricants (synovial fluid and hyaluronic acid) was measured, to help elucidate the mechanism that these lubricants may employ to reduce friction in vivo (Aim 3). We identified that synovial fluid and hyaluronic acid have only 2-5x the viscosity of water (and PBS) at shear rates relevant to cSCA sliding tests and intact joints, and they enhance cartilage’s ability to maintain high fluid load support (and thus low friction) only under conditions that support tribological rehydration.
Finally, we utilized live, mechano-biologically active articular cartilage explants in the cSCA along with different combinations of active sliding, sedentary compression, sliding speed, and bathing lubricants to replicate ‘pathophysiological’ through ‘truly physiological’ sliding environments (Aim 4). We showed that when tribological rehydration was compromised during testing by slow-speed sliding, ‘pathophysiological’ environments and high surface cell death were observed. Conversely, when tribological rehydration was preserved by high-speed sliding (and lubricant supplementation), ‘semi-’ and ‘truly physiological’ sliding environments and suppressed cell death were realized. Pilot data was also collected to investigate the relationship between injurious impact, cell health, and their influence on tribological rehydration and lubrication under physiologically consistent sliding environments (Aim 5) in order to better elucidate why impacts lead to detrimental cartilage function and health.
Overall, the work described in this dissertation leverages the recently re-interrogated and tribologically unique cSCA configuration to investigate the influence of sliding environment on cartilage function and biology in health and injury, and to foster the development of a more holistic lubrication structure to explain how cartilage may function both on the benchtop and in the joint, informing not just knowledge of basic biomechanics, but future translational approaches to targeting articular cartilage damage and disease, and extending joint longevity.