Cationic Tantalum Oxide Nanoparticle and Neutral Iodixanol Contrast Agents Alter Cartilage Mechanical Properties

Early detection of cartilage degeneration remains a critical unmet clinical need. While contrast-enhanced computed tomography shows promise in detecting early structural and compositional changes in articular cartilage, full adoption into clinical use requires a comprehensive understanding of how contrast agents affect cartilage function, including potential biomechanical alterations. This study investigates how exposure to two contrast agents, pre-clinical ultrasmall cationic tantalum oxide nanoparticles (Ta₂O₅-cNPs) and neutral iodixanol, approved for clinical use, affect the mechanical and frictional properties of articular cartilage. Biomechanical and tribological properties of osteochondral samples (n = 60) from adult bovine stifle joints (N = 9) were systematically assessed before and after contrast agent immersion using friction testing, stress-relaxation, and dynamic loading protocols. The effect of solid and charged contrast agents on extracellular matrix stiffness and fluid-flow properties was studied using finite element modeling, which enabled interpretation of the stress-relaxation response and extraction of constituent-specific mechanical parameters. The results demonstrate that Ta₂O₅-cNP uptake softens extracellular matrix of cartilage as non-fibrillar matrix modulus decreases (linear mixed model, p < 0.001). Both contrast agents reduce permeability and viscosity of cartilage. These findings highlight the sensitivity of articular cartilage mechanics to contrast-agent uptake and distribution within the tissue. The results underscore the importance of carefully considering nanoparticle charge and size together with other physicochemical properties, such as composition, concentration, surface chemistry, and tissue retention, when designing contrast agents for cartilage imaging or therapy.