Effects of Botulinum Toxin Type A and Argireline on Dermal Collagen Remodeling and Skin Biology in a Flap Model

Botulinum toxin type A (BoNT-A) is increasingly recognized for tissue-level effects beyond neuromuscular blockade, but its impact on dermal collagen composition remains incompletely characterized. Acetyl hexapeptide-8 (Argireline) is a SNAP-25 mimetic cosmeceutical peptide whose biological activity at the tissue level is unclear. This study evaluated the effects of BoNT-A, Argireline, and their combination on dermal collagen type I/III and Substance P (SP) expression in a flap model.

Forty female Wistar rats were allocated to four groups (n = 10): saline control, BoNT-A, Argireline, and BoNT-A + Argireline. Subdermal injections were administered at six points one week before elevation of a 9 × 3 cm caudally based McFarlane flap. Flap survival was quantified on day 10 using planimetric analysis. Collagen type I/III was assessed using picrosirius red staining under polarized light, and SP expression was evaluated immunohistochemically.

Flap survival did not differ significantly among groups (p = 0.327). Collagen composition differed significantly: BoNT-A-containing groups demonstrated lower type I and higher type III collagen compared with control and Argireline groups (p < 0.001). Argireline alone produced a collagen profile indistinguishable from control. SP expression was significantly elevated in the combination group compared with control and Argireline (p = 0.002).

BoNT-A shifted dermal collagen toward a less mature profile without improving flap survival. Injectable Argireline produced no detectable tissue-level effect under the tested conditions. Increased Substance P expression in the BoNT-A-containing groups represents an exploratory, predominantly BoNT-A-associated neurogenic signal warranting dedicated study. These findings highlight a dissociation between macroscopic tissue viability and dermal remodeling responses.

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