Comparison of the effects of intra-articular injections of Hyaluronan and its chemically cross-linked derivative (Hylan G-F20) in normal rabbit knee joints

Objective Intraarticular injection of native hyaluronan (HA) or a cross-linked derivative are commonly utilized in the treatment of osteoartrithis. Unlike from native hyaluronan, the crosslinked HA derivative is a gel containing also other chemical entities. This study compares the local tolerability of these different preparations in normal rabbit knees, in order to provide further information on their biological effects. Methods Synovial fluids were aspirated after single or repeated weekly injections (up to three) of the therapeutic agents and cell count was determined in a Burker chamber and in an automatic cell counter. The percentage of the different cell types was determined by light microscopy in semithin sections of fixed synovial fluid cytocentrifugate. Fragments of synovial membrane were also morphologically analyzed. Results In the synovial membrane no signs of inflammation were evident either after a single or repeated injections of native Hyaluronan (Hyalgan(R) or Artz(R)). In addition, the cell recruitment and the percentage of cell types in the synovial fluid was not statistically different from saline treated joints. After 3 weekly injections of the crosslinked HA derivative (Hylan G-F20, Synvisc(R)) about 50% of the treated joints appeared slightly inflamed and in these joints a statistically significantly higher cell content was determined in the synovial fluid compared to placebo and native Hyaluronan treatment. In addition an unexpectedly high percentage of eosinophils was found in the synovial fluid and in the synovial membrane of slightly inflamed joints treated with crosslinked HA. Conclusion The data obtained after repeated intra-articular injections in normal rabbit knee joints confirm the safety profile of native Hyaluronan.