Systemic filgrastim increases maximum load to failure of repaired Achilles tendons in rats: a biomechanical, histopathological, and immunohistochemical study

Abstract Background Achilles tendon healing involves prolonged extracellular matrix remodeling and incomplete restoration of native mechanical properties. Granulocyte colony-stimulating factor may support tissue repair, but its independent effect on tendon healing remains unclear. This study evaluated two doses of systemic filgrastim after primary Achilles tendon repair in rats. Methods Thirty-six female Wistar albino rats were randomized to a control group, a low-dose filgrastim group receiving 10 µg/kg/day, or a high-dose filgrastim group receiving 30 µg/kg/day, with 12 animals per group. After bilateral Achilles tenotomy and primary repair, filgrastim or 5% dextrose was administered subcutaneously for five days. On postoperative day 28, healing was assessed by tensile testing, Updated Bonar scoring, Picrosirius Red birefringence, collagen type I alpha 1 chain, collagen type III alpha 1 chain and platelet endothelial cell adhesion molecule-1 immunohistochemistry, and serum cytokine measurements. Maximum force was the primary outcome; histological and immunohistochemical parameters were secondary outcomes, and serum cytokines were exploratory. Group comparisons were performed using one-way ANOVA, Welch’s ANOVA, or the Kruskal–Wallis test, as appropriate. Results Maximum force was significantly higher in the low-dose group (57.49 ± 13.98 N) and high-dose group (62.01 ± 14.64 N) than in controls (24.17 ± 11.97 N; both p < 0.001), with no significant difference between filgrastim doses. Total Updated Bonar scores were lower in both filgrastim groups and lowest in the high-dose group. Filgrastim was associated with a higher red–orange/green birefringence ratio, higher collagen type I alpha 1 chain and lower collagen type III alpha 1 chain immunoreactivity, and lower microvessel density. In exploratory analyses, serum interleukin-6 was nominally lower and tumor necrosis factor-α nominally higher in the high-dose group, whereas interleukin-1β and transforming growth factor-β did not differ significantly among groups. Conclusions Short-term systemic filgrastim administration during the early postoperative period increased the maximum load to failure of repaired Achilles tendons at 28 days and was associated with a more mature histological and immunohistochemical remodeling profile. The higher dose was associated with more favorable values for selected histological parameters but did not further increase maximum force; therefore, these data do not establish a dose–response relationship.