Oxygen enrichment mediated by calcium peroxide loaded gelatin methacrylate hydrogel eradicates periodontal biofilms

The low oxygen environment of the periodontal pocket favors pathogenic anaerobes' growth, biofilm formation, and quick recurrence after periodontal treatment. In contrast, oxygen is detrimental to anaerobes, such as Porphyromonas gingivalis (P. gingivalis), since they lack a complete anti-oxidation mechanism to detoxify the oxygen challenge. Therefore, consistently feeding pathogenic anaerobes with abundant oxygen would be an effective strategy to combat them. Here, we reported injectable oxygen-generating hydrogels as oxygen mediators to alleviate the local anaerobic environment and eliminate periodontal pathogens. Gelatin methacrylate (GelMA) hydrogels loaded with calcium peroxide (CPO) possessed excellent injectability and exhibited burst releases of oxygen within 24 h with a 40 % oxygen tension peak. CPO-GelMA hydrogels with CPO concentrations of 5, 10, and 15 % reduced 60, 99, and 89.9 % viable P. gingivalis, respectively. Five percentage CPO-GelMA hydrogel downregulated gingipain and fimA gene expression in P. gingivalis without resistance development. Moreover, the CPO-GelMA hydrogels remarkably prevented biofilm formation and eradicated both monospecies and multispecies bacterial biofilms. In conclusion, CPO-GelMA hydrogels exert remarkable antimicrobial and antibiofilm effects on subgingival biofilms, providing a promising strategy for periodontal treatment.