EFFECTIVENESS OF SINGLE VERSUS REPEATED TOPICAL APPLICATION OF 0.05% TRETINOIN ON COLLAGEN SYNTHESIS IN ACUTE FULL-THICKNESS WOUNDS: AN EXPERIMENTAL STUDY IN RATS

Background: Effective wound healing is essential in surgical and traumatic care, especially for full-thickness injuries.
Tretinoin, a topical retinoid, has been reported to accelerate healing by stimulating fibroblast proliferation, angiogenesis, epithelialization, and collagen deposition. Its action involves modulation of TGF-β, which upregulates fibroblast-derived bFGF and promotes matrix remodeling. However, the comparative effectiveness of single versus repeated applications remains unclear.
Methods: A randomized post-test only experimental study was conducted on 27 healthy male Wistar rats (200–250 g), divided into three groups (n=9): control (A), single application of 0.05% tretinoin (B), and repeated applications for five consecutive days (C). Standardized 20 mm full-thickness dorsal wounds were created and stented with silicone rings. Group A received no treatment; Group B received a single application; Group C received daily applications for five days.
On day 5, wound tissues were collected for analysis of collagen density (Masson’s Trichrome) and TGF-β expression
(immunohistochemistry). Data were analyzed using Shapiro-Wilk, Kruskal-Wallis, and Mann-Whitney U tests.
Results: Repeated topical application of 0.05% tretinoin (Group C) resulted in the highest collagen density and TGF-β
expression among the three groups. Statistical analysis confirmed a significant difference in both parameters (p < 0.05).
Post hoc comparisons showed that Group C differed significantly from Group A in both collagen density and TGF-β
expression, while Group B (single application) did not differ significantly from either Group A or C. Histological
evaluation supported these findings, revealing denser, more organized collagen fibers and stronger TGF-β
immunostaining in Group C.
Conclusion: Repeated topical application of 0.05% tretinoin significantly enhances collagen synthesis and TGF-β
expression in acute full-thickness wounds. This study supports the therapeutic potential of repeated tretinoin dosing in promoting faster and more robust wound healing, with implications for optimizing topical treatment regimens in clinical practice.