Multifunctional eugenol-enriched PEO-based electrospun and photo-crosslinked scaffolds for wound healing applications

• PEO electrospun nanofibrous membranes functionalized with eugenol-based bioactives. • Photo-crosslinking enhanced scaffold stability and mechanical integrity. • Cytocompatible scaffolds exhibiting strong antibacterial and anti-biofilm activity. • Promoted rapid wound closure in both 2D and 3D healing models. • Multifunctional scaffolds enabling infection control and tissue regeneration. The development of multifunctional wound dressings that simultaneously prevent infection and promote tissue regeneration remains a critical challenge in regenerative medicine. In this study, electrospun poly(ethylene oxide) (PEO)-based nanofibrous membranes were functionalized with eugenol (EU) and eugenol methacrylate (EUMA) as bioactive agents. The membranes were subsequently photo-crosslinked to enhance structural stability and biomedical applicability. Different concentrations of bioactive compounds were evaluated, and the optimized formulations produced scaffolds with uniform, defect-free fibers averaging 316–340 nm in diameter. Physico-chemical characterization confirmed that the scaffolds possess mechanical robustness, flexibility, hydrophilicity, and permeability, which are key requirements for effective wound dressing performance. Both EU- and EUMA-functionalized scaffolds were cytocompatible and non-toxic. In addition, they exhibited notable antibacterial and anti-biofilm activity. Membranes containing 5% EU showed superior inhibition of Gram-positive bacterial growth, whereas those incorporating 5% EUMA provided enhanced cytoprotective and pro-regenerative effects. In vitro wound-healing assays using human mesenchymal stromal cells demonstrated that EUMA-functionalized scaffolds achieved an 85% reduction in wound width within 24 h in a 2D model. Consistently, in a 3D reconstructed human epidermis model, both EU- and EUMA-doped scaffolds accelerated wound closure by approximately twofold compared to undoped PEO. This study thus provides a previously unexplored structure-function comparison between native eugenol and its methacrylated derivative incorporated into photo-crosslinked electrospun PEO scaffolds, elucidating how chemical modification governs the balance between antimicrobial and regenerative performance. Overall, the developed PEO-based nanofibrous scaffolds offer a scalable, cost-effective, and versatile platform for next-generation smart wound dressings designed to support both infection control and tissue repair.