Skin Wound Dressings Based on Biocompatible Nanofibers Loaded with the Mastoparan-Mo Peptide to Promote Regeneration and Control Infection in Skin Wounds

Abstract Skin wounds represent a major clinical challenge, particularly in chronic nonhealing cases associated with conditions such as diabetes, vascular disorders, prolonged immobilization, or trauma. These wounds involve a prolonged inflammatory process that impairs tissue regeneration, increases the risk of opportunistic infections, and further hinders healing, reducing quality of life and even threatening patient survival. Moreover, wound treatment significantly increases healthcare costs, making wound management a growing public health concern. In this study, we fabricated a series of skin wound dressings based on biocompatible nanofiber mats loaded with the antimicrobial and pro-regenerative peptide Mastoparan-Mo. We evaluated their physicochemical properties, antibacterial activity against clinically relevant bacteria, and pro-regenerative effects. These wound dressings exhibited well-defined ultrastructural organization, appropriate physicochemical properties, high hydrophilicity, and controlled-release behavior, supporting their potential as functional biomaterials. Moreover, they displayed antibacterial activity against several bacterial species commonly associated with skin infections and showed high biocompatibility in in vitro assays, promoting cell proliferation and motility in a model of primary human dermal fibroblasts. To assess the translational potential of these biomaterials, we used a model based on ex vivo human skin cultures derived from healthy skin explants, which preserve native tissue architecture and cellular heterogeneity. Using this model, we demonstrated that nanofiber wound dressings loaded with the Mastoparan-Mo peptide promote tissue regeneration in skin injuries within a physiologically relevant platform that closely mimics human skin in vivo.