Background: Chronic wounds, such as diabetic ulcers, pressure sores, and burns, remain a global healthcare burden due to the rising threat of antibiotic-resistant infections and impaired healing processes. Traditional antibiotics are losing efficacy, but antimicrobial peptides (AMPs), part of the innate immune system, offer a revolutionary solution. Purpose: This review analyzes 34 potent AMPs with dual antimicrobial and wound-healing properties, highlighting their mechanisms, efficacy, and clinical potential. Results: AMPs disrupt microbial membranes via pore formation (e.g., Magainin 2, Myxidin, Lucifensin), cell wall inhibition (e.g., Nisin, Plectasin), and intracellular interference (e.g., PR-39 inhibits DNA replication). Notably, these peptides target multi-drug resistant strains like MRSA (Temporin A, Indolicidin) and P. aeruginosa (Esculentin-1a, Cathelicidin-DM). Beyond killing microbes, AMPs actively promote wound healing through angiogenesis (LL-37, Epinecidin-1), keratinocyte proliferation (Temporin A, hBD-2), collagen synthesis (LL-37, Esculentin-1a), and anti-inflammatory modulation (AW1, Chensinin-1b). Despite their promise, challenges such as salt sensitivity (hBD-2), potential cytotoxicity (MSI-78), and resistance development (S. aureus to LL-37) persist. To overcome these limitations, researchers are exploring structural engineering (non-natural amino acids), advanced delivery systems (hydrogels for Kn2-7, TS-CATH), and synergistic combinations (Bactenecin + IDR-1018). Remarkably, some AMPs like Cathelicidin-NV promote wound healing without direct antimicrobial activity, while S100A12 uses "nutritional immunity" (Zn2⁺ sequestration) to inhibit H. pylori. Conclusion: In conclusion, AMPs represent a transformative frontier in wound care, combining broad-spectrum antimicrobial activity, immunomodulation, and tissue regeneration. Further research into optimized delivery and clinical trials will unlock their full potential as next-generation therapeutics. © The Author(s), under exclusive licence to Springer Nature B.V. 2025.
