The effect of sonication on simulated osteoarthritis. Part I: effects of 1 MHz ultrasound on uptake of hyaluronan into the rabbit synovium.

High molecular weight (MW) hyaluronan (HA) preparation is considered to be more biologically active than HAs of lower MWs. However, many of the HA preparations currently used to treat osteoarthritis (OA) have lower MWs by the enhanced penetration of HA molecules into the synovial lining cells. In this study, we determined the effectiveness of sonophoresis on the delivery of high MW HA into synovial membrane using an animal model of OA. A total of 1000 kDa (HA1000) and 3000 kDa (HA3000) HA were labeled with fluorescein and injected into the knees of rabbits. Low-intensity continuous ultrasound at 1 MHz, 400 mW/cm2 was applied to the knees for 10 min treatment bid. Synovial fluid analysis revealed increased absorption and fluorescence microscopy showed deeper penetration of both HA1000 and HA3000, more so with the latter. Histologic examination indicated that ultrasound treatment resulted in no apparent damage to the synovial membrane. These results suggest that simultaneous sonication with HA injection might compensate for the short half-life of HA. Consequently, this dual treatment would render HA a far more effective tool in the management of OA.

The effect of sonication on simulated osteoarthritis. Part II: alleviation of osteoarthritis pathogenesis by 1 MHz ultrasound with simultaneous hyaluronate injection.

In our previous study, we demonstrated the effects of ultrasound (US) on the delivery of hyaluronan (HA) into the synovium, even at molecular sizes as high as 3000 kDA. We hypothesized that a combined therapy with US and HA would have synergistic effects on alleviating the pathogenesis of osteoarthritis (OA). In the present study, we evaluated the effectiveness of sonication on the progress of induced OA in rabbits. We measured the cartilage degradation and inflammation, synovial fluid amount along with protein content and, finally, performed histologic analyses of the integrity of the cartilage and synovium. Low-intensity continuous US at 1 MHz, 400 mW/cm2 was applied to the knees for 10 min bid. Combined treatment with US and HA most strikingly reduced total synovial fluid volume and also significantly alleviated the OA-induced accretion of total protein, proteoglycan and prostaglandin E2 in the synovial fluid. It also attenuated the release of collagen type II and matrix metalloproteinase-3 in the OA-induced joint to normal levels. Histopathology revealed that combined HA and US treatment also reduced the severity of OA-induced structural damages in the cartilage and synovium. The effectiveness of HA with regard to the alleviation of OA pathogenic changes can be greatly enhanced by the simultaneous treatment with HA and US.