Concentration-Dependent Inhibition of Hypertrophic Scar Formation by Botulinum Toxin Type A in a Rabbit Ear Model.

Abstract

Hypertrophic scar (HS), as a disappointing result of wound healing, adversely affects the patient, both physically and psychologically. Botulinum toxin type A (BTXA) has been revealed to prevent and improve HS. We conducted this study to assess the effect of different BTXA concentrations on inhibiting HS in a rabbit ear model. Eight healthy New Zealand long-eared rabbits were included in the experiment for modeling. Four wounds of 1 cm in diameter were created on both ears, which separately received an injection of a given BTXA concentration immediately after surgery. On postoperative days 40, scar tissue was obtained and subjected to hematoxylin and eosin (HE) staining for the hypertrophic index (HI) and immunohistochemical staining for CD31, Ki67, and transforming growth factor-beta 1 (TGF-β1) expression. The HI was assessed for scar proliferation, and CD31 and Ki67 expression were used to assess the effect of BTXA on angiogenesis and fibroblast proliferation, respectively. All rabbits healed well without infection or mortality. From the HE staining, the HI showed a significant decrease with increasing BTXA concentration (p < 0.05). BTXA also inhibited angiogenesis and TGF-β1 expression in a concentration-dependent manner, with significant differences between the groups (p < 0.05). BTXA inhibited fibroblast proliferation with increasing BTXA concentration. However, there was no significant difference between the 0.5 U/0.1 ml and 0 U/0.1 ml groups (p > 0.05). Immediate postoperative BTXA injection inhibited angiogenesis, fibroblast proliferation, and TGF-β1 expression in a concentration-dependent manner, thus suppressing HS formation in rabbit ears. 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 https://www.springer.com/journal/00266 .