Polycaprolactone and poly(vinyl alcohol) electrospun single-layer nanofiber materials loaded with novel antibacterial LEGO-LPPO for advanced wound dressing

Wound infection remains a major obstacle to effective healing and highlights the need for advanced dressings that combine antimicrobial activity with favorable biological properties. In this study, we developed electrospun nanofibrous wound dressings based on polycaprolactone (PCL) and poly(vinyl alcohol) (PVA) loaded with the novel antibacterial agent LEGO-LPPO 5. In parallel, we established an improved multigram synthesis of LEGO-LPPO 5 to support further translational development. The biological effects of LEGO-LPPO 5 were evaluated in human dermal fibroblasts and HaCaT keratinocytes, followed by its incorporation into electrospun nanofibrous carriers and characterization of the resulting materials in terms of morphology, antibacterial activity, and drug release kinetics. In vivo efficacy was assessed in a prophylactic mouse model of Staphylococcus aureus-impaired wound healing. LEGO-LPPO 5 at bactericidal concentrations was generally well tolerated by keratinocytes and did not impair keratinocyte migration, whereas fibroblasts exhibited slightly greater sensitivity at higher concentrations or upon prolonged exposure. Release studies demonstrated marked differences between the two polymer systems: PVA-based materials showed rapid release, which could be slowed by thermal stabilization, whereas PCL-based materials exhibited slower release that was substantially accelerated during lipase-catalyzed degradation. All LPPO-containing materials displayed antibacterial activity, with the strongest effects observed for PVA- and PCL-based formulations containing higher LPPO loadings. In the mouse model, the fast-release PVA-based formulation provided the most pronounced protection, resulting in near-complete prevention of severe infection together with a marked reduction in bacterial burden. These findings identify LEGO-LPPO-loaded nanofibrous dressings as a promising platform for topical infection control and support their further development as advanced wound care materials.