Intra-articular distribution and residence time of Hylan A and B: a study in the goat knee

This study evaluates the viscosupplementation material Hylan A and B in relation to its: (1) joint distribution, residence time and mechanism of removal and/or degradation, and (2) associated synovial fluid leukocyte response, in a goat model.

One green fluorophore was covalently bound to the Hylan A low molecular weight (MW) molecule (viscous fluid fraction) and a second red fluorophore was covalently bound to Hylan B high MW molecule (globule gel-like fraction). Goats were anesthetized and the right knee received 0.5 ml of test material or unbound fluorophore dyes. Gross and histological serial evaluations were performed over an 8-week period.

By 24 h, the non-covalently linked control labels were not present in the tissues. For the covalently linked labels, the green fluorophore Hylan A diminished rapidly in intensity grossly but persisted to 28 days within the superficial synovial and articular cartilage layers in histologic sections. The red fluorophore linked Hylan B was seen only as globules in the synovial fluid. Mononuclear cells remained attached to these globules for 28 days and showed phagocytosis of the globules as well as the green fluorophore Hylan A. The globules were absent at 56 days after injection. The synovial fluid leukocyte count peaked at 24h (mean 9767 cells/mm(3) +/- 8574 S.D.) and declined by 7 days.

The smaller MW Hylan was removed more rapidly than the higher MW Hylan. The globules were degraded by a different mechanism involving monocytes/macrophages on the surface of the higher MW globules.