Abstract

Purpose: Post-operative adhesion band formation is a serious post-surgery complication with a highly detrimental impact on patient morbidity and health care costs. In this study, we aimed to investigate the repurposed potential of a safe and FDA-approved drug, metformin, in attenuating post-surgical adhesion band formation in Achilles tendon surgeries in an animal model.

Methods: Wistar albino rats were divided randomly into three groups: sham, positive control, and metformin-treated groups (n=6). We administered Metformin 100 mg/kg orally for 21 days. Achilles tendon tissue sections were stained with Hematoxylin-Eosin and Masson's trichrome to assess the accumulation of inflammatory cells and collagen deposition. Spectrophotometric analysis was performed on tissue samples to determine oxidative stress markers. According to Tang and Ishiyama scoring systems, Achilles tendon adhesion properties were compared.

Results: Using the Tang and Ishiyama scoring system, we showed that metformin significantly decreased the length, density, grading, and severity of adhesion bands at surgery sites (***p<0.001). Pathologic morphological changes and oxidative stress markers decreased in tendon tissue samples of metformin-treated rats compared to control (**p<0.01, ***p<0.001). Moreover, administration of metformin markedly decreased collagen deposition, fibrosis accumulation, and fibrosis quantity score as visualized by Masson’s trichrome staining in tissue sections (*p<0.05).

Conclusion: These results suggest that metformin, with its potent anti-inflammatory and anti-fibrotic properties, can be repurposed as a potential therapeutic molecule for preventing post-operative adhesion band formation.

Keywords: Metformin, achilles tendon, fibrosis, inflammation, post-surgical adhesion bands.