The role of hyaluronic acid in inflammation and wound healing.

We have previously hypothesized that hyaluronic acid (HA) and fibrin specifically interact and help orchestrate the early stages of the inflammatory response and wound healing (J. Theoretic. Biol. 119, 219, 1986). In the present work we have extended studies to confirm this prediction. Several approaches were used to show that human fibrinogen specifically binds to hyaluronic acid. In addition, this latter glycosaminoglycan greatly stimulated the in vitro formation of fibrin clots induced by thrombin. The presence of hyaluronic acid also altered the structure of the final fibrin gel. Removal of circulating hyaluronic acid in blood is therefore probably vital in order to maintain normal haemostasis. Evidence is presented to suggest that an endocytic receptor recycling process is responsible for the ability of liver endothelial cells to perform this function and remove HA from the blood. Although hyaluronic acid levels are initially low in a blood clot, the proposed wound-healing model explains why and how HA levels increase and the functional and structural significance of this polysaccharide during wound healing.