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In this study, we introduced a piezocatalytic nanoparticle-constructed \u201cnano-toothbrush\u201d as a noninvasive strategy for oral biofilm removal. The dextran-mediated biofilm affinity of the nano-toothbrush induced localized oxidative stress under ultrasound irradiation, effectively disrupting biofilms and inhibiting pathogenic bacteria. This efficacy was evidenced by the removal of ex vivo biofilms from periodontitis patients. Importantly, the selective action of the nano-toothbrush minimized the damage to mouse fibroblasts and human immortalized oral epithelial cells, affirming its biosafety. In vivo studies showed that the nano-toothbrush significantly inhibited the cell viability of\n                    <jats:italic toggle=\"yes\">Porphyromonas gingivalis<\/jats:italic>\n                    , effectively suppressed alveolar bone resorption, and alleviated inflammatory responses in a rat periodontitis model while concurrently preserving the diversity of the oral microbiome. 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