Effects of Botulinum Toxin Type A on Microvessels in Hypertrophic Scar Models on Rabbit Ears

Abstract

Background. Although Botulinum Toxin Type A (BTXA) has been applied to scar prevention and treatment, the mechanisms still require further exploration. Objective. To investigate the effects of BTXA on microvessels in the hypertrophic scar models on rabbit ears. Methods. Eight big-eared New Zealand rabbits (males or females) were selected to establish scar models. One ear of each rabbit (4 models in each ear) was selected randomly to be injected with BTXA immediately after modeling and included in the treated group, while the opposite ear was untreated and included in the control group. The growth of scars in each group was observed and recorded, and 4 rabbits were sacrificed on days 30 and 45 after modeling. Then, scar height was measured by hematoxylin-eosin (HE) staining, vascular endothelial growth factor (VEGF) expression was detected by immunohistochemical (IHC) testing, and microvessel density (MVD) was calculated based on CD34 (human hematopoietic progenitor cell antigen). Results. The wounds in each group were well healed and free from infection or necrosis. On days 30 and 45, the scar height, MVD value, and VEGF expression in the treated group were lower than those in the control group (P<0.05). For the treated group, the above indicators on day 45 were lower than on day 30 (P>0.05). Besides, there was a positive correlation between the MVD value and the VEGF expression in the treated group (P<0.05). Conclusion. The injection of BTXA immediately after modeling inhibits VEGF expression and reduces angiogenesis, thereby inhibiting hypertrophic scar formation.

Safety and efficacy of botulinum toxin type A in preventing and treating scars in animal models: A systematic review and meta‐analysis

“…Ten articles did not provide detailed data. Thus, 11 articles were included in the analysis 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 (Figure 1 ).…”

Efficacy and safety of botulinum toxin type A for postoperative scar prevention and wound healing improvement: A systematic review and meta‐analysis

“…56,57 Other profibrotic factors, including interleukin-6, connective tissue growth factor, and vascular endothelial growth factor (VEGF), were also downregulated, 55 and angiogenesis was inhibited in parallel. 58,59 BTXA attenuated the scar contraction through negatively affecting the expression of α-smooth muscle actin and myosin II in fibroblasts. 53,54,60,61 Collagen deposition and remodeling processes were likewise altered in response to BTXA.…”

“…TGF‐β/Smad and ERK pathways could be the signaling pathway mediating BTXA function, 54 and meanwhile, other pathways, such as PTEN and JNK pathways, were also proposed to contribute to the inhibitor effect of BTXA on fibroblasts 56,57 . Other profibrotic factors, including interleukin‐6, connective tissue growth factor, and vascular endothelial growth factor (VEGF), were also downregulated, 55 and angiogenesis was inhibited in parallel 58,59 . BTXA attenuated the scar contraction through negatively affecting the expression of α‐smooth muscle actin and myosin II in fibroblasts 53,54,60,61 .…”

Current Research of Botulinum Toxin Type A in Prevention and Treatment on Pathological Scars

“…Besides, scar hyperplasia is related to the creation of scar vessels, and vascular endothelial growth factor (VEGF), angiogenin, and basic fibroblast growth factor are all involved in scar vessel forming. In a rabbit ear model, Zhou 24 demonstrated that BTXA injection reduced angiogenesis and prevented the formation of hypertrophic scars by inhibiting the expression of related cytokines such as VEGF.…”