Measurement of local diffusion and composition in degraded articular cartilage reveals the unique role of surface structure in controlling macromolecular transport.

Abstract

Developing effective therapeutics for osteoarthritis (OA) necessitates that such molecules can reach and target chondrocytes within articular cartilage. However, predicting how well very large therapeutic molecules diffuse through cartilage is often difficult, and the relationship between local transport mechanics for these molecules and tissue heterogeneities in the tissue is still unclear. In this study, a 150 kDa antibody diffused through the articular surface of healthy and enzymatically degraded cartilage, which enabled the calculation of local diffusion mechanics in tissue with large compositional variations. Local cartilage composition and structure was quantified with Fourier transform infrared (FTIR) spectroscopy and second harmonic generation (SHG) imaging techniques. Overall, both local concentrations of aggrecan and collagen were correlated to local diffusivities for both healthy and surface-degraded samples (0.3 > R² < 0.9). However, samples that underwent surface degradation by collagenase exhibited stronger correlations (R² > 0.75) compared to healthy samples (R² < 0.46), suggesting that the highly aligned collagen at the surface of cartilage acts as a barrier to macromolecular transport.