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

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 Cu²⁺ release. This combined effect is primarily driven by substantial contact-induced membrane damage, and the presence of released Cu²⁺ 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.