Cationic tantalum oxide nanoparticle contrast agent for micro computed tomography reveals articular cartilage proteoglycan distribution and collagen architecture alterations
Jiri Jäntti, Anisha Joenathan, C. Fugazzola, Juuso Tuppurainen, Juuso T. J. Honkanen, Juha Töyräs, P. René van Weeren, Brian D. Snyder, Mark W. Grinstaff, Hanna Matikka, Janne Mäkelä
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.