Synergistic Antibacterial Remineralization: A Bioprocessing-Inspired Single-Step Nanoparticle-Induced Liquid Precursor Strategy for Functional Dentin Repair

Bacterial invasion compromises the inherent reparative capability of dentin, leading to caries progression. Designing an effective strategy to simultaneously restore the dentin structure and combat oral biofilms remains a great challenge. This study presents a single-step biomimetic approach that employs carboxyl-functionalized gold nanoparticles (AuNPs-COOH) as a noncollagenous protein analogue to generate nanoparticle-induced liquid precursor (NILP) for synergistic dentin regeneration and antibacterial therapy. The AuNPs-COOH stabilize amorphous calcium phosphate precursors and induce intrafibrillar mineralization, thereby restoring the hierarchical architecture and mechanical properties of dentin (elastic modulus: 24.42 GPa; hardness: 1.06 GPa), closely matching those of sound dentin (24.84 and 1.15 GPa, respectively) and surpassing conventional polymer-induced remineralization. The remineralized dentin exhibits dual antibacterial functionalities activated by near-infrared (NIR) light: photothermal effect and photodynamic generation of reactive oxygen species. This NIR-activated system significantly inhibits <i>Streptococcus mutans</i> biofilm formation <i>in vitro</i>, reducing biofilm biomass to 10-20% of control levels under both immediate and long-term conditions, and demonstrates robust antibacterial efficacy <i>in vivo</i>. Furthermore, the remineralized dentin exhibits excellent biocompatibility with dental pulp stem cells and minimal systemic toxicity in animal models. The AuNPs-COOH-mediated NILP system thus offers a synergistic strategy for functional dentin regeneration and caries prevention.