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Updated: Feb 20, 2026

A Mouse Model of Mechanotransduction-driven, Human-like Hypertrophic Scarring
Published on: November 29, 2024
Radiofrequency therapy attenuates hypertrophic scar formation in rabbit ears by modulating the TGF-β1/Smad3 signaling
Tingting Zhang1, Canbin Liu1, Xintian Zhang1
1Burn & Wound Repair Department, Fujian Medical University Union Hospital, Fuzhou, Fujian 350001, China; Fujian Burn Institute, Fujian Medical University Union Hospital, Fuzhou, Fujian 350001, China; Fujian Burn Medical Center, Fujian Medical University Union Hospital, Fuzhou, Fujian 350001, China; Fujian Provincial Key Laboratory of Burn and Trauma, Fujian Medical University Union Hospital, Fuzhou, Fujian 350001, China.
Objective:
To investigate the impact of radiofrequency (RF) therapy on the formation of hypertrophic scars in rabbit ears and its regulatory effect on the TGF-β1/Smad3 signaling pathway.
Methods:
Six male New Zealand white rabbits aged 3-5 months were selected. Six full-thickness skin defect wounds were created on the ventral side of each ear (72 total). Wounds were observed on days 0, 7, 14, and 21, and the scar formation rate was calculated on day 21. Right ear scars (n = 36) served as controls; left ear scars (n = 36) received RF therapy. After 14 days, scar pigmentation and pliability were observed, and scar tissue samples were collected. Additionally, 36 healthy wound tissue samples from the ventral side of the ears of three age-matched healthy rabbits were used as the healthy group. All samples underwent HE staining to calculate the scar elevation index (SEI), Masson staining to observe collagen morphology, immunohistochemistry (IHC) to detect TGF-β1 and Smad3 protein expression, and RT-qPCR to measure TGF-β1 and Smad3 mRNA levels.
Results:
By postoperative day 21, all wounds had formed hypertrophic scars, with a scar formation rate of 100 %. After 14 days of intervention, the RF therapy group showed significantly improved scar pliability and tissue morphology compared to the scar control group (P < 0.05), with no significant change in pigmentation. The SEI values and the protein and mRNA expression levels of TGF-β1 and Smad3 in the RF therapy group were significantly lower than those in the scar control group (P < 0.05).
Conclusions:
RF therapy can improve the pliability of scar tissue, promote the normal arrangement of collagen fibers in the dermis, and reduce the deposition of collagen fibers, thereby inhibiting the formation of hypertrophic scars in rabbit ears. The mechanism may be related to the inhibition of the TGF-β1/Smad3 signaling pathway.

