Reduction of adhesion formation by postoperative administration of ionically cross-linked hyaluronic acid

Abstract

Objective: To examine the efficacy of various formulations of hyaluronic acid (HA), including HA ionically cross-linked with trivalent iron, in animal models of adhesion formation.

Design: Hyaluronic acid formulation of varying concentrations and cross-linked densities were prepared and evaluated in a rabbit uterine horn model and a rabbit sidewall model.

Setting: ETHICON, Inc., Somerville, New Jersey.

Subject(s): New Zealand White rabbits.

Intervention(s): Test formulations were applied as intraperitoneal instillates after surgery.

Main outcome measure(s): Adhesion formation was assessed at 7 and 14 days (sidewall and uterine horn model, respectively).

Result(s): Hyaluronic acid that was not ionically cross-linked was ineffective in reducing adhesions in these models even at high viscosity, whereas the ionically cross-linked formulations of HA with trivalent iron were highly effective. Efficacy improved with increased levels of ionic cross-linking. Flowable gels, which could be delivered readily by syringe and cannula, also were effective when administered at a site remote from injury and with saline present.

Conclusion(s): Whereas previous studies show that HA was effective in reducing adhesions peripheral to the site of injury, HA ionically cross-linked with trivalent iron was effective in reducing adhesions at all sites. From these studies, a formulation of HA ionically cross-linked with trivalent iron, 0.5% Ferric Hyaluronate Gel (LUBRICOAT; ETHICON, Inc., Somerville, NJ), was identified for subsequent clinical evaluations.