M6a-Per1-Targeting Quercetin Hydrogel Aids Periodontal Bone Regeneration

Periodontal disease ranks third among noncommunicable illnesses, behind cancer and cardiovascular disease, and is a major cause of numerous diseases with extremely high death rates. However, elucidating the processes of periodontal disease and promoting periodontal bone regeneration remains a challenge. This study employed OMSCs to model periodontal oxidative stress in vitro, assessing quercetin’s antioxidant and reparative effects. meRIP-seq identified m6A-modified genes linked to quercetin’s mechanism, validated in vitro to pinpoint key targets. A quercetin-loaded injectable hydrogel was developed as a sustained-release "bone-enhancing factory," mitigating oxidative damage and promoting periodontal repair. Results demonstrated quercetin’s dual role in restoring OMSC function via m6A regulation of Per1 and enabling hydrogel-mediated tissue regeneration, offering a synergistic therapeutic strategy for periodontal defects. Quercetin enhances OMSCs' antioxidant activity, rescues differentiation (osteogenic/chondrogenic/lipogenic), and reduces apoptosis via m6A/Per1 regulation. Delivered via nano-bioglass hydrogel, it sustains release and promotes Per1-dependent osteogenesis. This approach effectively accelerates periodontal bone regeneration in rats, linking m6A modification to tissue repair. This drug-carrying system, made up of nanoscale bioglass microspheres and a light-cured injectable hydrogel, allows effective drug particle loading and cementation in the dynamic and moist periodontal environment. Furthermore, the system demonstrated the ability to stimulate OMSC osteogenic differentiation in a Per1-dependent manner, which ultimately promoted periodontal bone repair, suggesting that this system has potential for clinical periodontal therapy.