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Botulinum Toxin Type A Alleviates Hypertrophic Scar Formation in a Rabbit Ear Model by Inhibiting the TGF-β1/Smad Pathway

Aesthetic Plast Surg. 2026 Jun 15. doi: 10.1007/s00266-026-05984-z. Online ahead of print.

ABSTRACT

BACKGROUND: Postoperative hypertrophic scarring represents a prevalent clinical challenge, with current therapeutic approaches demonstrating limited efficacy. Previous studies have confirmed the scar-inhibitory properties of Botulinum toxin type A (BTA), though its precise molecular mechanisms require further elucidation. This study aims to explore the molecular pathways through which BTA attenuates hypertrophic scar formation using an established auricular cicatricial model in rabbits.

METHODS: Sixteen healthy New Zealand white rabbits underwent hypertrophic scar modeling. Post-modeling, therapeutic interventions were administered as follows: BTA (4U) was injected at the edge of the wound in the BTA group and the combined group, whereas, decorin (50 µg) was injected at the edge of the wound in the decorin group and the combined group. Decorin administration was repeated following a seven-day interval. The control group was administered an equivalent volume of normal saline. The scar height, collagen deposition and TGF-β1 expression level were measured by histological examination. Protein expression profiles were evaluated through immunoblotting techniques.

RESULTS: Our results revealed that hypertrophic scars were reduced in all treatment groups compared with the control group. BTA- and/or decorin-treated group had lower scar height, collagen deposition and TGF-β1 expression level at week 4 and week 8. BTA and/or decorin effectively suppressed the Smad2/3 phosphorylation cascade, inhibited MMP2 enzymatic activity, and reduced the protein expression of α-SMA and collagen I.

CONCLUSION: BTA improves the appearance of scar, reduces collagen deposition, and decreases the degree of scar formation by inhibiting the TGF-β1/Smad signaling pathway in a rabbit ear model.

NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

PMID:42298167 | DOI:10.1007/s00266-026-05984-z

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