Core-shell Cu-PBG@PDA@PHMB nanospheres enable contact killing and Cu2⁺ release for rapid infected wound repair

Core-shell-shell PPH nanospheres were designed for antibiotic-free wound therapy. • Cationic PHMB and released Cu 2+ cooperatively eliminate bacteria and biofilms. • PDA layer regulates pH-responsive Cu 2+ release with favorable hemocompatibility. • PPH promotes HUVEC migration in vitro and neovascularization in vivo . • Accelerated wound remodeling was achieved with enhanced collagen deposition. Bacterial infection and biofilm formation pose major obstacles to wound healing. To address these challenges, we designed a core-shell nanocomposite, Cu-PBG@PDA@PHMB (PPH), consisting of a copper-doped phosphate glass (Cu-PBG) core, a polydopamine (PDA) interlayer, and a polyhexamethylene biguanide (PHMB) outer shell. The PPH nanospheres exert a complementary antibacterial effect via contact-killing and ion release: the cationic PHMB shell disrupts bacterial membranes through electrostatic interaction, whereas the PDA layer mediates pH-responsive Cu 2+ release. This combined effect is primarily driven by substantial contact-induced membrane damage, and the presence of released Cu 2 ⁺ ions further enhances this membrane-disruptive action, ultimately leading to efficient bacterial killing. In vitro evaluations demonstrated that PPH exhibited notable antibacterial activity against Staphylococcus aureus ( S. aureus ) and Escherichia coli ( E. coli ), markedly reduced mature biofilm biomass, and substantially disrupted biofilm integrity. Furthermore, the nanocomposite exhibited favorable biocompatibility and significantly promoted endothelial cell migration. In vivo experiments in a S. aureus -infected murine wound model demonstrated that PPH treatment was associated with accelerated wound closure, reduced bacterial burden, and improved angiogenesis and collagen deposition. This nanoplatform represents a promising therapeutic strategy for the clinical management of infected wounds.