Manipulation of Surface Electrical Charge on Nanocomposite Membranes Confers Wide Spectrum Bactericidal Effects and Promotes Tissue Regeneration

Abstract Utilization of electro‐responsive biomaterials with antibacterial properties is advantageous for facilitating septic wound healing and tissue regeneration. However, the dose‐response effects of electrical stimuli from these materials against bacteria are not rigorously characterized, and achieving synergy of bactericidal and pro‐regenerative effects of biomaterials remains a major challenge. Here, a graded series of flexible BaTiO 3 /P(VDF‐TrFE) electroactive nanocomposite membranes (EMs) are developed with varying surface charge intensities, to serve as antibacterial dressing for septic wound healing. EMs display broad‐spectrum antibacterial effects against both Gram‐positive and Gram‐negative bacteria in a dose‐dependent manner, depending on the magnitude of their surface electrical potential. Mechanistically, the surface charge of EMs increase intracellular levels of reactive oxygen species within bacteria cells, which in turn caused oxidative damage to the bacterial membrane, thereby suppressing bacterial activity and biofilm formation. Moreover, in vivo studies demonstrated that EMs effectively inhibited S. aureus infection and accelerated wound healing in a mouse skin defect model, as well as ameliorated P. gingivalis‐ mediated periodontal inflammation in a mouse periodontitis model. Hence, this study optimizes the antibacterial properties of electroactive materials and characterizes the dose‐response effects of surface electrical charge against bacteria, thus validating the therapeutic applications of electroactive biomaterials in combating bacterial infection.