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

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 formulations 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 showed 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.