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Effects of Rhinoplasty on Smile Esthetic and Gingival Appearance: Commentary.

skin wound healing following trauma or surgery is imperfect and results in scar formation. We have read with interest the metaanalysis of Chen et al about the effectiveness and safety of botulinum toxin type a (BTX-A) in minimizing surgical scar. The authors identified 8 placebo-controlled and double-blind clinical trials involving 267 patients. The quality of the trials included in this review was mixed. Selective reporting of outcomes was a major flaw. Although the present study shows that local injection of BTX-A could mitigate scar formation, no reliable tool to estimate the severity of scar formation could be determined. Authors have failed however to investigate the mechanism by which BTX-A could improve scar formation. In their introduction, the authors have summarized the use of BTX-A in various conditions for which temporary muscular paralysis when injected locally is beneficial. They have stated that BTX-A might be effective in suppressing scar hypertrophy due to chemodenervation of striated muscle by acting on the presynaptic neuron to prevent the release of acetylcholine. Although this is a welldocumented effect of BTX-A, it is difficult to understand how this effect could be translated into better scar formation. BTX-A effect on myofibroblasts is less evident; nevertheless, it is postulated that less myofibroblats-mediated contractions due to functional denervation result in decreased tension on wound edges with improved scarring. Although this mechanism has been the traditional accepted mode of action of BTX-A, we have demonstrated few years ago in an experimental animal study that the observed effect of BTX-A on scar formation is most probably due to modulation of various wound healing cytokines rather than simple denervation effect of striated muscle fibers. In this study we assessed the effect of BTXA in the healing process through parameters like transepidermal water loss (TEWL), transforming growth factor beta (TGF-beta1), and tumor necrosis factor alpha (TNF-alpha), as well as histological alterations. The results of this study demonstrated an acute and immediate increase of TNF-alpha 21-fold than control, followed on day 3 by an increase in TGF-beta1 levels; levels of both cytokines subsequently decreased sharply as healing progressed. Histology revealed delayed lower grade inflammation and relatively better and faster tissue regeneration with earlier epithelialization and epidermal regeneration. Botox-treated wounds showed also accelerated fibroblast proliferative response. Xiao et al have demonstrated in 2010 that fibroblasts isolated from tissue specimens treated with BTX-A showed slower growth than fibroblasts without such treatment. They also demonstrated higher TGF-beta1 production by fibroblasts not treated by BTX-A. These seemingly contradictory results to ours are very confusing. This, however, does not need to be so. As we have demonstrated, cytokine levels have increased sharply initially following BTX-A injection then gradually decreased. Their levels thus change drastically depending on the stage of wound healing at which their determination has been made. The process of wound healing is characterized by a complex and sensitive balance between activation and inhibition of inflammation and is well orchestrated and coordinated by a fluctuating signaling transduction of a diversity of growth factors, cytokines, and extracellular matrix components. More research is needed in the future, as recommended by the authors, to demonstrate the effectiveness of BTX-A on wound healing and scar formation. Research, however, should concentrate on its wound healing modulation effect.