Stimuli-activable hollow Cu2O@C/N doped paste for the prevention of white spot lesions in orthodontic treatments.

White spot lesions (WSLs) are the most common complication of orthodontic treatment, compromising dental health and significantly affecting aesthetics. To address this clinical challenge, this study aims to develop a dual-functional therapeutic strategy that simultaneously promotes the remineralization of demineralized enamel and inhibits the activity of cariogenic bacteria, thereby achieving effective prevention and treatment of WSLs. A hollow double-shell structured Cu2O@N/C nanozyme (H-Cu2O@N/C) was synthesized using a one-step hydrothermal method. The thin nitrogen-doped carbon shell significantly enhances the material's stability in aqueous environments and reduces the systemic toxicity of cuprous oxide nanocrystals. By employing bioinspired encapsulation technology, H-Cu2O@N/C was incorporated into a biodegradable adhesive matrix made of gelatin methacryloyl (GelMA) and sodium alginate, forming the Cu/GS composite ointment. The acidic plaque biofilm activates the peroxidase-like activity of H-Cu2O@N/C, effectively catalyzing low-dose H2O2 into highly toxic hydroxyl radicals (·OH) for targeted antibacterial action. Crucially, Cu/GS acts as a nucleation template, crosslinking with abundant Ca2 + to attract PO43⁻ from saliva, thereby promoting hydroxyapatite growth on the enamel surface and accelerating rapid remineralization. The Cu/GS ointment overcomes the limitations of existing single-function therapeutic materials through its synergistic "antibacterial-remineralization" dual-functional mechanism. In vitro biomimetic model experiments confirm its ability to simultaneously inhibit WSL progression and repair early-stage enamel defects, demonstrating significant potential for clinical intervention in orthodontic-related WSLs.