Nintedanib alleviates polypropylene mesh-induced adhesion in rabbit ventral herniorrhaphy

Abstract

Abstract BACKGROUND: Nintedanib (previously known as BBIF 1120) was approved by the United States Food and Drug Administration and European Medical Agency to treat idiopathic lung fibrosis in the year 2014 and 2015, respectively. It is now gaining interest for its anti-fibrotic activity in other organs and disease conditions. Although a surgical mesh is used as a mainstay therapy for herniorrhaphy, postoperative peritoneal adhesion with a polypropylene mesh is a significant drawback. This study aims to assess the efficacy of nintedanib in preventing postoperative adhesion incited with a polypropylene mesh in a rabbit model of ventral hernia. MATERIALS AND METHODS: Ventral hernia was induced surgically in ten adult healthy New Zealand White rabbits of either sex. Hernioplasty was performed with a polypropylene mesh, and the rabbits were randomly allocated into two groups to receive either oral 1 ml sterile water or 100 mg nintedanib in 1 ml of sterile water for 7 days. The adhesion of the implanted mesh with the intra-abdominal organs was assessed clinically, by histological and ultrastructural studies with scanning electron microscopy (SEM) at 30 days postoperatively. RESULTS: All rabbits were clinically healthy for 30 days post-surgery with no complication at the site of surgery. The incidence of peritoneal adhesion and tenacity was less in the nintedanib group versus the control group (P = 0.00105). Histopathological and SEM evaluations also indicated less fibrosis and adhesion in the nintedanib-treated group versus control. CONCLUSION: Our results show successful prevention of mesh-associated adhesion with nintedanib, but further studies on the mechanistic pathway, pharmacokinetics, dose standardization, and evaluation of systemic side effects are warranted.