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Tranilast Modulates Cellular and Matrix Remodeling in Achilles Tendon Healing: A Comprehensive Histological and Biomechanical Analysis
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DOI：10.3390/bioengineering13070768.png)
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Abstract
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Background: Tranilast is an anti-inflammatory and antifibrotic agent known to inhibit TGF-β-mediated fibroblast activation and matrix overproduction. Although its therapeutic potential has been explored in several fibrotic and inflammatory conditions, its effects on tendon healing remain unknown. This study aimed to evaluate the histopathological and biomechanical impact of tranilast in a rat Achilles tendon repair model. Methods: Thirty-two male Sprague–Dawley rats were randomly assigned to four subgroups, control (C-15, C-30) and tranilast-treated (TR-15, TR-30), and sacrificed on postoperative day 15 or 30. Tranilast (30 mg/kg/day) or placebo was administered intraperitoneally. Tendons were subjected to biomechanical testing (maximum load to failure) and histological evaluation using Bonar and Movin scoring systems on Hematoxylin + Eosin (HE)-, Masson Trichrome (MT)- and Alcian Blue (AB)-stained slides. Additional analyses included Sirius Red histochemistry with assessment of collagen type I/III intensity and polarization ratio, as well as H-scores for collagen I and III. Results: Tranilast produced marked improvements in histopathological healing. Both TR-15 and TR-30 exhibited significantly lower Bonar and Movin scores compared with controls, with reductions in tenocyte degeneration, ground-substance accumulation, collagen disorganization, vascularity, and hyalinization (all p < 0.01). However, biomechanical strength did not differ significantly among the groups (p = 0.3948). Sirius Red analysis and collagen I/III H-scores revealed no significant differences in collagen composition or polarization ratio. Histological improvements were therefore not accompanied by measurable changes in collagen subtype distribution or maximum load to failure. Conclusions: Tranilast was associated with favorable histopathological changes during Achilles tendon healing, including improvements in cellular morphology, matrix organization, and overall Bonar and Movin scores. However, these findings were not accompanied by significant differences in collagen composition or biomechanical strength within the 30-day observation period. Further long-term and mechanistic studies are warranted to determine whether these histopathological changes translate into functional improvements in tendon biomechanics. Accordingly, the present findings should be considered preliminary and exploratory.
Keywords:
tranilast
Achilles tendon
tendon healing
Bonar score
Movin score
biomechanics
collagen
rat model
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