Nanoparticle sensors and lubricants for degenerative articular cartilage
Lawson, Taylor Burgess
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Articular cartilage is a highly organized, anisotropic tissue lining the ends of bones within synovial joints. Composed primarily of water, collagens, proteoglycans and chondrocytes which synergistically give rise to the tissue's mechanical and tribological properties. Fluid pressurization and resistance to fluid flow within the porous extracellular matrix of cartilage, coupled with the low hydraulic permeability of the tissue endow the tissue with a viscoelastic response to loading and aid to reduce the coefficient of friction between articulating surfaces, with the pressurized fluid supporting 95% of applied loads. Experiencing millions of articulations throughout an average lifetime, articular cartilage possesses distinct biotribological properties. These require effective lubrication, mediated by the synergistic interaction between fluid and boundary lubricants, to provide a low coefficient of friction and prevent wear at the cartilage surface. Osteoarthritis is the progressive deterioration of articular cartilage and synovial joint structure and function, leading to softer and wear prone tissue on account of altered biochemical composition of the extracellular matrix. Plain radiography remains the most accessible tool and the current standard of care to visualize musculoskeletal diseases and injuries (e.g., osteoarthritis), but cannot directly visualize soft tissues or cartilage, and diagnoses are based solely on boney changes, which occur in the later stages of the disease. Coupled with no way to quantitatively assess tissue health prior to irreversible deterioration, there remains no cure for osteoarthritis. Integral to OA pathology are concomitant changes in the biochemical composition of synovial fluid that result in deterioration of rheological properties, contributing to increased cartilage wear. To address both the lack of quantitative diagnosis methods and lack of chondroprotective therapies, this dissertation presents a dual faceted approach to quantitatively image articular cartilage health, coupled with lubrication strategies to improve cartilage lubrication, and preserve cartilage tissue. This dissertation describes the synthesis of tantalum oxide nanoparticles of varying surface charges for use as contrast agents for rapid, minimally invasive, non-destructive, and quantitative contrast-enhanced computed tomography to assess both the biochemical content and biomechanical integrity of articular cartilage. Ex vivo contrast enhanced computed tomography attenuation using the nanoparticle contrast agent reveals correlations between attenuation and the mechanical and biochemical properties of the tissue. The lubrication strategy described within this dissertation involves introducing a rolling ball element between two surfaces to reduce friction. In this strategy, either single, globular macromolecules or nanoparticles are employed as ball bearings between articulating surfaces to reduce friction when asperities on the surfaces are in direct contact. Rheological characterization and construction of classical Stribeck curves using the lubricant formulations reveal that introducing the rolling element reduces the coefficient of friction during boundary lubrication, while leaving the rheological properties of the base fluid intact. Ex vivo cartilage mechanical testing involving shear deformation under varying speeds and loads reveal improved biotribological performance compared to pure synovial fluid or saline.
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