The residence time of hyaluronan (HA) in knee joint synovial fluid (SF) was investigated using a rabbit anterior cruciate ligament transection (ACLT) model. The aims of this study were to assess, at 7 and 28 days after surgery, the 1) HA concentration and molecular mass (Mr) distribution in the SF, 2) endogenous replenishment of HA after saline washout, 3) HA residence times in the SF, and 4) synovium and subsynovium cellularity of the knee joints of rabbits subjected to ACLT, compared to sham-operated and nonoperated control joints.


Adult NZW rabbits underwent ACLT or sham surgery on one hind limb, while each contralateral limb was the nonoperated control. On day 7 or 28 after surgery, the joints were aspirated for SF, lavaged with saline, and injected with saline or polydisperse HA, and samples were obtained for analysis at set time points up to 8 hours after injection. Joint fluid samples were analyzed for the concentration and Mr distribution of HA to calculate the HA residence time constant.


Analysis of HA concentrations and Mr distributions showed 1) loss of high-Mr HA in the SF on day 7 and a shift toward a lower-Mr distribution on day 28, 2) endogenous replenishment of high-Mr HA after washout, and 3) Mr-dependent loss of HA from the knee joints after ACLT, particularly on day 7 postsurgery. The HA residence time decreased with decreasing HA Mr (residence time ∼27 hours with an Mr load of 7,000–2,500 kd, to ∼7 hours with an Mr load of 250–50 kd). HA residence time also decreased (by ∼70%) in the knee joints on day 7 after ACLT. The subsynovium of the joints subjected to ACLT displayed increased cellularity and neovascularization on days 7 and 28 postsurgery.


The residence time of HA in the SF is transiently decreased after ACLT, suggesting that a biophysical transport mechanism is responsible for the altered composition of the SF after joint injury or during inflammation.