Antimicrobial Peptides in Wound Healing and Skin Regeneration: Dual Roles in Immunity and Microbial Defense

Although penicillin transformed antibiotic therapy, rising antimicrobial resistance (AMR) has limited its effectiveness, creating a need for new approaches in wound healing. Antimicrobial peptides (AMPs) are promising candidates due to their rapid membrane-disrupting action, immunomodulatory effects, and ability to target drug-resistant pathogens, though their specific roles in promoting wound healing are still not fully understood. This review aims to provide a comprehensive synthesis of the current evidence on the dual role of AMPs as both antimicrobial and immunomodulatory agents in the context of wound healing. Recent studies published between 2020 and 2025 were comprehensively reviewed, focusing on the mechanisms by which AMPs contribute to pathogen elimination, immune regulation, tissue repair, and inflammation resolution. AMPs not only exhibit rapid membrane-disruptive activities against a wide range of pathogens but also influence immune cell behavior, particularly by promoting macrophage polarization toward a reparative M2 phenotype, modulating cytokine and chemokine network, and maintaining T-cell homeostasis. Their ability to simultaneously control infection and regulate inflammation positions AMPs as promising candidates for advanced wound care strategies. The dual antimicrobial and immunomodulatory functions of AMPs represent a synergistic mechanism essential for effective wound recovery. Understanding and harnessing these properties can drive the development of innovative therapies, such as AMP-integrated smart biomaterials and targeted peptide delivery systems, offering new solutions for both acute and chronic wound management.