Anti-Fibrotic Effect of Tacrolimus on Preventing Adhesion after Achilles Tendon Surgery in a Murine Model.

Abstract

Background: Peritendinous adhesion as a common post-surgical complication usually occurs as a result of a large portion of sports and hard job-related injuries. This study aims to evaluate the repurposed potential of the immunosuppressive approved drug, tacrolimus, in decreasing adhesion band formation post-Achilles tendon surgeries in an animal model.

Methods: Rats were randomly assigned to four groups control, sham with surgical intervention but no adhesion, positive control group with surgical transection and adhesion received no treatment, tacrolimus group was the same as the positive control group except that rats were treated with 2 mg/Kg/day tacrolimus orally for 21 days. The anti-inflammatory and fibrinolytic properties of oral tacrolimus treatment in attenuating the formation of adhesion bands were analyzed by One-way ANOVA or the Kruskal-Wallis test.

Results: Tacrolimus decreased the length (P=0.001), density (P=0.001), grading (P=0.023), severity (P=0.001), and thickness (P=0.008) of post-surgical adhesion bands compared to the untreated group. Histopathological changes and recruitment of inflammatory cells to the tendon tissue sections were attenuated in the tacrolimus-treated group (P=0.001) in comparison with the positive control group. Compared to the untreated group, tacrolimus treatment decreased the expression of IL-1β (P=0.059) in the tendon tissue, but the difference was not statistically significant. Moreover, tacrolimus elicited anti-fibrotic responses by reducing the expression of tissue growth factor-β (TGF-β) in the tendon and inhibiting collagen deposition, fibrosis quantity (P=0.001), fibrosis grading (P=0.001), and total fibrosis scores (P=0.001), as visualized by Masson's trichrome staining.

Conclusion: These results support the protective properties of tacrolimus in decreasing post-operative adhesion band formation in the animal model.