Although the complete contrast agent diffusion into human articular cartilage in vitro took more than 12h, significant apparent correlations were revealed between the spatial proteoglycan (PG) and contrast agent distributions already after 2h of immersion. At the stage of incomplete penetration, however, the spatial contrast agent concentration distribution cannot directly reflect the true PG distribution as the Donnan equilibrium has not been reached. However, in degenerated cartilage the diffusion rate increases. Obviously, this can lead to the reported correlation between the bulk PG content and the bulk contrast agent concentration already at the early stages of diffusion.

Charged contrast agents have been used both in vitro and in vivo for estimation of the fixed charge density (FCD) in articular cartilage. In the present study, the effects of molecular size and charge on the diffusion and equilibrium distribution of several magnetic resonance imaging (MRI) and computed tomography (CT) contrast agents were investigated. Full thickness cartilage disks (Ø = 4.0 mm, n = 64) were prepared from fresh bovine patellae. Contrast agent (gadopentetate: Magnevist((R)), gadodiamide: Omniscan, ioxaglate: Hexabrix or sodium iodide: NaI) diffusion was allowed either through the articular surface or through the deep cartilage. CT imaging of the samples was conducted before contrast agent administration and after 1, 5, 9, 16, 25 and 29 h (and with three samples after 2, 3, 4 and 5 days) diffusion using a clinical peripheral quantitative computed tomography (pQCT) instrument. With all contrast agents, the diffusion through the deep cartilage was slower when compared to the diffusion through the articular surface. With ioxaglate, gadopentetate and gadodiamide it took over 29 h for diffusion to reach the near-equilibrium state. The slow diffusion of the contrast agents raise concerns regarding the validity of techniques for FCD estimation, as these contrast agents may not reach the equilibrium state that is assumed. However, since cartilage composition, i.e. deep versus superficial, had a significant effect on diffusion, imaging of the nonequilibrium diffusion process might enable more accurate assessment of cartilage integrity.

The present results suggest that CECT can be used to diagnose proteoglycan depletion in spontaneously degenerated articular cartilage with a clinical pQCT scanner. Possibly, the in vivo use of clinical pQCT for CECT arthrography of human joints is feasible.

When rhCII was used to repair cartilage defects, the repair quality was histologically incomplete, but still the rhCII-repairs showed moderate mechanical characteristics and a slight improvement over those in spontaneous repair. Therefore, further studies using rhCII for cartilage repair with emphasis on improving integration and surface protection are required.