Effects of hyaluronic acid on fibroblast behavior in peritoneal injury

The process of intraperitoneal adhesion formation is affected by macrophages and fibroblasts which are major components of postsurgical peritoneal repair. Hyaluronic acid (HA) has been shown to affect cellular behavior. We studied the effects of HA on experimental adhesions in vivo and its in vitro effect on cultured postsurgical macrophages and fibroblasts. Experimental adhesions were facilitated by laparotomy and localized peritoneal controlled trauma in two groups of rats (A, B). Postoperatively, group A received intraperitoneal (ip) treatment by HA (1 mg/kg) for 7 days, and group B, ip saline. The rats were then reoperated upon, and adhesions scored. In vitro studies were performed on postsurgical macrophages and fibroblasts. Fibroblasts were obtained using a single-cell suspension technique by debridement of adhesions. The fibroblasts were cultured for 7 days, and their metabolic activity was assessed by the uptake of [3H]thymidine. Postoperative macrophages were obtained from the peritoneal fluid of the rats operated on, and their effect upon fibroblast [3H]thymidine uptake was studied in mixed cultures. The adhesion score of the HA-treated rats was smaller than the score of the saline-treated group. This observation suggests that ip treatment by HA may decrease adhesion formation in this rat model. [3H]Thymidine uptake by cultured postsurgical fibroblasts was significantly lower in the HA-treated group compared to that of controls. In vitro addition of HA to cultured "saline fibroblast" resulted in a significant decrease in [3H]thymidine uptake, suggesting a direct effect of HA on postsurgical fibroblast metabolism. However, [3H]thymidine uptake by fibroblasts in mixed cultures with macrophages obtained from HA-treated rats was significantly increased. These observations suggest that HA may affect the process of peritoneal healing by direct effect on fibroblast metabolic activity, and indirectly via modification of the macrophage-fibroblast interrelationship.