Cationic tantalum oxide nanoparticle contrast agent for micro computed tomography reveals articular cartilage proteoglycan distribution and collagen architecture alterations

Abstract

ObjectiveCationic tantalum oxide nanoparticles (Ta2O5-cNPs), as a newly introduced contrast agent for computed tomography (CT) of cartilage, offer quantitative evaluation of proteoglycan content and biomechanical properties. However, knowledge on the depth-wise impact of cartilage constituents on NP diffusion, particularly the influence of the collagen network, is lacking. In this study, we aim to establish the depth-dependent relationship between Ta2O5-cNP diffusion and cartilage constituents (proteoglycan content, collagen content and network architecture). MethodsOsteochondral samples (n = 30) were harvested from healthy equine stifle joints (N = 15) and the diffusion of 2.55 nm diameter cationic Ta2O5-cNPs into the cartilage was followed with µCT imaging for up to 96 hours. The diffusion-related parameters, Ta2O5-cNP maximum partition (Pmax) and diffusion time constant, were compared against biomechanical and depth-wise structural properties. Biomechanics were assessed using a stress-relaxation and sinusoidal loading protocols, whereas proteoglycan content, collagen content and collagen network architecture were determined using digital densitometry, Fourier-transform infrared spectroscopy and polarized light microscopy, respectively. ResultsThe Pmax correlates with the depth-wise distribution of proteoglycans (bulk Spearman’s ρ = 0.87, p < 0.001). More open collagen network architecture at the superficial zone enhances intake of Ta2O5-cNPs, but collagen content overall decreases the intake. The Pmax values correlate with the equilibrium modulus (ρ = 0.80, p < 0.001) of articular cartilage. ConclusionThis study establishes the feasibility of Ta2O5-cNPs for the precise and comprehensive identification of biomechanical and structural changes in articular cartilage via contrast-enhanced µCT.