Core-shell nanofibers integrating growth factor-loaded nanoparticles for spatio-temporal delivery in chronic wound healing

Effective chronic wound management increasingly relies on advanced delivery systems capable of providing spatio-temporal control over release of therapeutic agents. Such systems can localize treatment precisely at the wound site while coordinating the multiple bioactive cues, addressing the complex and sequential biological processes required for successful tissue repair. In this study, we present a composite core–shell nanofiber dressing designed to integrate epidermal growth factor (EGF)-loaded nanoparticles (NPs) and ciprofloxacin, addressing two key requirements of wound healing: rapid antimicrobial protection and promotion of tissue regeneration. Fabricated via a green coaxial electrospinning approach under aqueous conditions, the system features a polyvinyl alcohol core and a polyvinylpyrrolidone /hyaluronic acid shell. Nanoencapsulation was employed to protect the growth factor from harsh processing conditions and to enable precise delivery of EGF directly to the wound site. EGF-loaded NPs with an average diameter of around 170 nm were prepared by modified solvent diffusion and loaded into a nanofiber shell layer by dispersion in the polymeric solution. The successful formation of the core-shell architecture and homogeneous NPs loading was confirmed by TEM and confocal microscopy. Upon contact with wound exudate, the nanofiber dressing outer shell rapidly dissolves, enabling a fast release of EGF-loaded NPs, while simultaneously triggering sustained ciprofloxacin release from the core, enabling coordinated dual therapeutic delivery. The dressing exhibited antibacterial activity against both Gram-positive and Gram-negative bacteria, showed high biocompatibility and promoted effective in vitro wound closure in a scratch assay. By combining multiple encapsulation techniques, this dressing architecture enabled spatial segregation of therapeutic agents within the core and shell allowing coordinated and temporally controlled delivery at the wound site. We expect that this approach may support localized treatment, minimize off-target effects, and protect surrounding healthy tissue, potentially addressing the complex requirements of chronic wound healing and highlighting the promise of rationally engineered core–shell platforms for advanced wound care.