Amphibian-derived peptides as novel therapeutics for skin wound healing: Mechanisms, applications, and challenges.

Skin injury disrupts the body's primary barrier against pathogens and environmental insults, often leading to infection, delayed healing, and pathological scarring. Therefore, the development of effective wound-healing therapies remains a major clinical priority. Amphibian-derived peptides have attracted growing interest as a diverse group of bioactive molecules for wound repair. In addition to their antimicrobial effects, increasing evidence suggests that these peptides can regulate multiple stages of healing by modulating inflammation, promoting keratinocyte and fibroblast migration and proliferation, enhancing angiogenesis, and supporting extracellular matrix remodeling. This review summarizes current knowledge on the discovery and distribution of amphibian-derived wound-healing peptides and discusses recent findings on their biological activities, mechanisms of action, and potential applications. Rather than simply cataloguing reported peptides, we also assess the strength of the current evidence and discuss major translational challenges in the field, including insufficient mechanistic validation for some candidates, limited use of clinically relevant wound models, peptide instability, toxicity, and barriers related to formulation and delivery. We also discuss strategies that may improve peptide developability, including rational structural modification, biomaterial-based delivery systems, and translation-oriented preclinical evaluation. Overall, amphibian-derived peptides are a valuable source of multifunctional wound-healing agents, but their clinical development will require stronger mechanistic evidence, standardized efficacy assessment, and better translational design.