The Adjunctive Role of Botulinum Toxin A in Wound Healing and Scar Management

Wound healing is a complex process involving hemostasis, inflammation, proliferation, and remodeling. Chronic wounds (persisting beyond 6 weeks) and pathological scarring pose significant clinical challenges. These conditions not only impair patient quality of life but also impose heavy economic burdens on healthcare systems. BoNT/A has been widely studied and shows promise in promoting wound healing, reducing pathological scarring, and improving chronic wounds. However, the existing evidence base largely consists of low-level studies, including animal models, case reports, and small clinical trials. While these studies show positive outcomes, their efficacy and long-term safety need to be validated through high-quality large-scale clinical trials. Therefore, it is important to acknowledge the limitations of current evidence and emphasize the need for further research to provide more robust support.

To comprehensively review the potential roles and underlying mechanisms of BoNT/A in promoting wound healing, preventing pathological scarring, and treating chronic wounds, aiming to provide theoretical insights for clinical applications.

This review synthesizes existing literature on BoNT/A, focusing on its biological mechanisms in wound healing, including effects on inflammation, angiogenesis, fibroblast activity, and extracellular matrix (ECM) regulation. It also summarizes clinical evidence and combination therapies involving BoNT/A for adverse wound outcomes. A literature search was conducted in PubMed, Embase, and Web of Science using the terms "botulinum toxin A", "wound healing", "scar", and "chronic wounds". Publications from the past ten years were prioritized, with earlier landmark studies included when relevant. Both preclinical and clinical evidence was considered to provide a comprehensive overview.

BoNT/A exerts multifaceted effects: it inhibits inflammatory responses by reducing mediators like IL-6 and substance P; promotes angiogenesis via HIF-1α/VEGF and nitric oxide pathways; modulates fibroblast activity by suppressing TGF-β1/Smad and ERK signaling to reduce abnormal collagen deposition; and improves wound microenvironment by reducing tension and regulating sweat/sebum secretion. Combination therapies (e.g., with steroids, lasers, or hyaluronic acid) enhance efficacy in scarring and chronic wound treatment.

BoNT/A has been widely studied and most reports suggest a favorable short-term safety profile; however, current evidence is predominantly low-level (animal studies, case reports, small series) and all wound-care uses remain off-label, underscoring the need for adequately powered randomized trials and long-term safety data.

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