Keith E. Greenawalt

Remote Efficacy for Two Different Forms of Hyaluronate-Based Adhesion Barriers

ABSTRACT Background: Chemically modified sodium hyaluronate and carboxymethylcellulose (HA/CMC) membrane clinically reduces adhesion formation following surgery but was not designed for laparoscopic use. HA/CMC powder of identical chemical composition has been developed to allow for application laparoscopically. We compared the adhesion reduction efficacy of HA/CMC powder and film when applied directly to or remote from sites of surgical trauma. We also investigated the effect of the powder on wound healing. Materials and Methods: Two animal models of adhesion formation were used to evaluate efficacy: a rat peritoneal sidewall defect model and a rabbit cecal abrasion/sidewall defect model. The products were applied directly to the defect or the contralateral sidewall. Adhesions were examined seven days after surgery. In a separate study, the effect of the powder on healing was evaluated at 5, 7, and 28 days using a rat incisional wound strength model. Results: HA/CMC powder and film, when applied directly to the peritoneal defect, significantly reduced adhesions relative to the untreated control in both models. Remote applications of HA/CMC powder also reduced adhesions. In contrast, remote applications of HA/CMC film had no effect. HA/CMC powder did not significantly alter incisional wound strength at any of the timepoints tested. Conclusion: In our preclinical models, HA/CMC powder had similar adhesion reduction efficacy to HA/CMC film when applied directly to sites of trauma. In addition, HA/CMC powder reduced adhesions remote from the application site. Importantly, HA/CMC powder did not impair incisional wound healing. On the basis of these results, future investigation of HA/CMC powder is warranted.

A Membrane Slurry Reduces Postoperative Adhesions in Rat Models of Abdominal Surgery

BACKGROUND Sodium hyaluronate and carboxymethylcellulose (HA-CMC) membrane is an effective barrier material for limiting postoperative adhesions, but can be difficult to apply in certain situations due to its physical properties. We tested whether HA-CMC membrane hydrated in saline (slurry) is an effective alternative to HA-CMC membrane for preventing surgical adhesions in rat models of abdominal surgery. MATERIALS AND METHODS All studies were performed in rat cecal abrasion or sidewall defect models of adhesion formation. Adhesions were examined 7 d after surgery. In separate studies, the effects of variations in slurry composition, volume, and site of application on anti-adhesive properties were studied and compared with untreated controls. Finally, the effectiveness of HA-CMC membrane slurry for preventing adhesions was compared with that of conventional HA-CMC membrane. RESULTS Application of HA-CMC membrane slurry to traumatized tissue resulted in a significant reduction in the incidence of adhesions compared with untreated controls in both rat surgery models. Slurry was equally effective when applied in low and high film-to-volume formulations, but had minimal effect when applied in a small volume or at a location distal to the injury. Comparison of HA-CMC membrane slurry and conventional HA-CMC membrane indicated similar efficacy for reducing postoperative adhesions. CONCLUSIONS In rat models of abdominal surgery, HA-CMC membrane slurry reduced postoperative adhesion formation and may be an effective alternative for HA-CMC membrane in situations where its use is limited by its physical properties.

Adhesion formation to hemostatic agents and its reduction with a sodium hyaluronate/carboxymethylcellulose adhesion barrier†‡§

The impact of hemostatic agents on postoperative adhesion formation has not been well studied. We hypothesized that hemostatic agents would be a significant nidus for adhesion formation and that a resorbable barrier would effectively reduce adhesions to hemostatic agents. Four commercial hemostatic agents, each composed of a different biomaterial matrix, were implanted in female Sprague-Dawley rats, and adhesion formation was examined 7 days after surgery. In separate studies, the effects of serosal trauma (via cecal abrasion), added blood, and the presence of chemically modified sodium hyaluronate/carboxymethylcellulose (HA/CMC) barrier on adhesion formation to hemostatic agents were studied. Significant adhesions formed to hemostatic agents even in the absence of traumatized tissue. When applied after cecal abrasion, the incidence of adhesions to the hemostatic agents increased. Addition of blood to this model increased adhesion formation even further, causing adhesions in every animal in the study. An HA/CMC adhesion barrier reduced adhesions to hemostatic agents in the presence of serosal trauma and maintained effectiveness even in the presence of blood. In conclusion, hemostatic agents potentiated adhesion formation at the site of application in a model without trauma. In more challenging models, their adhesiogenic contribution was overwhelmed by trauma and blood. HA/CMC adhesion barrier applied over hemostatic agents at the time of surgery provided significant protection against postoperative adhesions in these preclinical models.