Nucleoside‐Based Hydrogel Platform Synergizes with Photothermal Effects for Enhanced Biofilm Eradication Against Periodontitis

ABSTRACT Periodontitis is a chronic inflammatory disease primarily driven by pathogenic biofilms, and affects more than 90% of the global population. The increasing prevalence of bacterial resistance, coupled with the protective nature of resilient biofilms, makes it challenging to achieve satisfactory therapeutic outcomes. In this study, an organic small molecule‐based photothermal reagent ( FNP ) with excellent photothermal property is designed by rational tailor of donor‐acceptor combinations, and a supramolecular nucleoside hydrogel ( ZBAg ) is developed via silver ion‐stabilized base pairing and dynamic boronate ester bonds. The ZBAg hydrogel exhibits a unique coordination mechanism distinct from the traditional intermolecular i ‐motif coordination mode. The ZBAg@FNP hydrogel is prepared by encapsulating FNP within ZBAg hydrogel, which demonstrates excellent biocompatibility and achieves controlled Ag ⁺ release triggered by localized hyperthermia. The ZBAg@FNP hydrogel can damage biofilm structure through photothermal therapy and then improves the penetration of Ag ⁺ into the biofilms, resulting in synergistic eradication of the biofilms of oral pathogenic bacteria ( Porphyromonas gingivalis and Streptococcus mutans ). ZBAg@FNP hydrogel treatment significantly reduces the levels of proinflammatory cytokines, increases the levels of anti‐inflammatory cytokines, and reduces alveolar resorption in periodontitis of rats. This study provides a new strategy for treating periodontitis, and offers insights into the design of antibiofilm materials.