Abstract

Objectives Persistent apical periodontitis (PAP) is a chronic, treatment-resistant condition characterized by periapical infection and bone resorption, often resulting in poor outcomes. This study developed a bioactive root canal sealer incorporating Fe₃O₄–PAMAM magnetic nanoparticles (NPs) to enhance sealing and inhibit osteoclast differentiation, thereby reducing periapical bone loss. Methods Fe₃O₄–PAMAM NPs were synthesized and characterized using zeta potential analysis, electron microscopy, FTIR spectroscopy, X-ray diffraction, and magnetometry. The biocompatibility and anti-osteoclastic activity were assessed in vitro via CCK-8 assays, TRAP staining, qPCR, flow cytometry, and immunocytochemistry. The sealing ability of the NP-modified sealer was evaluated by micro-computed tomography and confocal laser scanning microscopy (CLSM), while antibacterial activity was assessed using colony-forming unit counts and scanning electron microscopy. A rat PAP model was used to evaluate the therapeutic effects of the modified sealer. Transcriptomic analysis and gene editing were performed to elucidate the molecular mechanisms. Results Fe₃O₄–PAMAM NPs were successfully synthesized and integrated into a bioceramic root canal sealer. The NPs exhibited dose-dependent inhibition of osteoclast differentiation, reaching a plateau at 100 µg/mL. The modified sealer showed good cytocompatibility and significantly improved dentinal tubule penetration under magnetic guidance. In vivo , the sealer markedly reduced periapical bone resorption in a PAP model. Mechanistic studies revealed that the NPs downregulated NFATC1 expression by suppressing SIGLEC15, thereby attenuating osteoclastogenesis. Significance The Fe₃O₄–PAMAM-modified root canal sealer simultaneously enhances sealing and suppresses periapical bone loss via osteoclast inhibition, offering a promising strategy to address key pathological features of PAP and enhance long-term endodontic outcomes.