Dual antibacterial and antibiofilm strategy based on an injectable NO-releasing supramolecular hydrogel for periodontitis treatment.

Periodontitis, a microbially-driven chronic inflammatory disease intricately linked to systemic disorders, is conventionally managed through mechanical debridement supplemented with adjunctive antibiotic therapy. However, the anatomical complexity of deep periodontal pockets often impedes complete biofilm eradication, while the transient retention of therapeutics within these pockets and emerging antibiotic resistance undermine treatment efficacy. To address these challenges, we developed an injectable supramolecular hydrogel (Gel) incorporating PEHA/NONOate as a nitric oxide (NO) donor. This system leverages the hydrogel's shear-thinning properties for minimally invasive delivery into deep periodontal pockets, enabling sustained and controlled NO release. PEHA, as a polyamine-based NO donor, overcomes the inherent instability of gaseous NO through high-capacity storage and gradual liberation, thereby exerting potent antibacterial and biofilm-disrupting effects without inducing cytotoxicity. Our findings demonstrate that this innovative platform not only provides an effective solution for deep-tissue antimicrobial therapy but also has translational potential for managing other refractory infections.