Novel approaches to determine the role of diffusive and convective transport environments in articular cartilage function

Price, ChristopherArticular cartilage is the bearing material of our joints, covering the contacting surfaces of our bones. It facilitates our ability to move around, due to its ability to withstand the compressive loads incurred during activity and promote remarkably low coefficients of friction between articulating cartilage surfaces. Cartilage is incredibly resilient, successfully maintaining these critical functions for nearly the entire duration of one’s lifetime, unless it is compromised by joint disease, e.g. osteoarthritis. Osteoarthritis a common musculoskeletal disease that afflicts millions of people, with disease risk increasing with age, obesity, and history of joint injuries. It is characterized by progressive degradation of the cartilage, which makes movement difficult and painful, ultimately resulting in severe disability. The etiology of osteoarthritis remains unclear, but a mix of mechanical and biological factors are certainly involved. ☐ Cartilage is an avascular, biphasic, living tissue, in which its structure, mechanical function, molecular transport, and health are inextricably linked. Better understanding of the complex relationships between these phenomena is required to realize the improvements in characterizing and combating joint dysfunction necessary to reduce the tremendously large burden of osteoarthritis. Therefore, this dissertation focused on elucidating the relationships between cartilage transport, structure, and function through the development of novel experimental approaches to studying transport of fluid and solutes in cartilage in situ. ☐ Transport can be divided into two primary mechanisms, diffusion and convection, which govern the movement of all solutes (nutrients, waste products, signaling molecules etc.) in cartilage. Diffusion is the apparent movement of molecules along a concentration gradient, due to the Brownian motion of individual molecules. The rate of diffusion in cartilage is dependent on a combination of solute properties and properties of the extracellular matrix, linking transport to tissue structure. Convection is fluid movement that carries along solutes with its flow, in a process known as advection, and is driven by load-induced fluid pressurization during joint movement. Convective rates are determined by the magnitude of loading, type of loading, and matrix properties, linking transport to cartilage structural-functional relationships. ☐ The first part of this dissertation focused on identifying relationships between solute transport and cartilage structural changes during the progression of osteoarthritis. Confocal microscopy-based correlation spectroscopy techniques developed for the measurement of solute diffusivity in solution were validated in bovine cartilage, then applied to human osteoarthritic cartilage samples to determine the relationships between solute diffusivity, solute size, cartilage material properties, and cartilage composition. ☐ The second part of this dissertation focused specifically on the convection of fluid and advection of solute into cartilage induced by articulation. Using a novel combination of state-of-the art confocal imaging techniques and novel tribological testing configuration, it was found that sliding induced significant solute transport into cartilage, at a rate and extent much greater than that of diffusion alone. Interestingly, the enhancement effect was consistent for a wide range of solute sizes, which indicated the overwhelming effectiveness of sliding as a transport enhancement mechanism. ☐ The last part of this dissertation focuses on the influence of the pattern by which sliding, i.e. frequency of sedentary vs. active motion, on convective transport and tribomechanical function within cartilage, specifically tribological rehydration, and strain and friction magnitude. It was found that longer periods of static rest between sliding bout increased the levels of strain and friction experienced over the course of a simulated day of activity. The data in these last two parts of this dissertation demonstrated the importance of sliding and movement to the transport in cartilage and the tissues overall functional health.University of Delaware, Department of Mechanical EngineeringPh.D