Prevention of intra-abdominal adhesions by a hyaluronic acid gel; an experimental study in rats

Abstract

Background In 80% to 90% of the patients intra-abdominal adhesions occur after abdominal surgery, which can cause small-bowel obstruction, chronic abdominal pain, female infertility and difficulty during reoperation. A novel crosslinked hyaluronic acid gel is evaluated regarding its anti-adhesive capacities in an ischemic button model in rats. Method 51 adult, male Wistar rats from a registered breeder, received eight ischemic buttons each and were treated with hyaluronic acid gel (HA, HyaRegen©), hyaluronic acid carboxymethylcellulose (HA-CMC, Seprafilm©) or no anti-adhesive barrier. After 14 days, the animals were sacrificed and adhesions were scored macroscopically. The number of buttons and organs involved in adhesions were recorded. Per animal, one button with adhesions and one without adhesions was explanted for qPCR analysis. Mann-Whitney U, Fisher’s exact and Wilcoxon signed rank test were used for data analysis. A p-value of 0.05 was considered significant. Results Macroscopic evaluation of adhesion formation did not differ between the groups. The number of organs involved in adhesions in the HA gel group was significantly lower compared to HA-CMC (p = .041) and the control group (p = .012). A significantly, 1.36-fold higher clec10a (p = 0.25), 1.80-fold higher cd163 (p = 0.003) and 5.14-fold higher mmp1 expression (p = 0.028) was found in ischemic buttons with adhesions compared to buttons without adhesions. Conclusion HA gel application reduces the number of organs involved in adhesions in an ischemic button model, but no overall reduction in adhesion formation was encountered. Macrophage subtype 2 polarization and high mmp1 expression are associated with adhesion formation. Further investigation is needed in the exact pathophysiologic process of adhesion formation and the role of macrophage polarization.