Development of a Sirolimus-eluting Mesh to Reduce Intra-Abdominal Adhesions

Abstract

Postoperative intra-abdominal adhesions are a significant clinical problem. This project addresses the potential novel role for a sirolimus-eluting hydrogel in the setting of postoperative adhesions caused by polypropylene hernia repair mesh. We review recent literature on adhesion pathogenesis, and examine the progress in development of anti-adhesion agents and strategies. We hypothesize an antiproliferative and antifibrotic agent such as sirolimus may minimize or prevent the process at critical steps in the pathway. A mouse model was developed using a 1x1 cm2 polypropylene mesh implanted into the peritoneal cavity. This study revealed that the addition of an agarose hydrogel to the adhesiogenic mesh significantly reduced adhesion incidence, severity and tenacity, and adding sirolimus to the hydrogel further significantly reduced adhesion surface area. Sirolimus has been used in many novel clinical settings for its antifibrotic properties; this work supports its consideration with agarose hydrogel as a prophylactic against postoperative intra-abdominal adhesions.