Effects of hyaluronan on cell proliferation and collagen synthesis: a study of rabbit flexor tendons in vitro

Hyaluronan (HA), a high-molecular-weight polysaccharide, has been suggested to play a possible role during the early stages of healing of a variety of connective tissues and when topically applied to decrease the formation of adhesions following tendon surgery. As the mechanisms of HA actions are still being discussed, this study was designed to assess the effects of HA on cell proliferation and synthesis of matrix components of deep flexor tendons in a well-defined culture system. Cell proliferation, measured as the radioactive 3H-thymidine uptake by cultured segments of rabbit flexor tendons, was inhibited by the addition of HA to the culture medium. HA of molecular weight 0.5 x 10(6) inhibited the uptake significantly at concentrations within the range of 0.1-2.0 mg/mL, HA of molecular weight 1.6 x 10(6) at 0.5-2.0 mg/mL, and HA of molecular weight 3.6 x 10(6) at 1.0-2.0 mg/mL, as compared to matched control groups. At the concentration of 2 mg/mL, HA of the molecular weights of 0.5, 0.8, 1.6, and 3.6 x 10(6) equally inhibited cell proliferation. No effect on synthesis of matrix components, measured as the radioactive incorporation of 35S-sulfate, 3H-hydroxyproline, and 3H-proline by cultured segments of rabbit flexor tendons, was observed. These findings show that exogenously applied HA may act as a modulator of flexor tendon fibroblast proliferation, indicating a possible mechanism for antiadhesive effects following administration after flexor tendon surgery.