Engineering Smart Bimetallic Ionic-Site MOF Nanozyme Nanocomposites for Microenvironment-Responsive Dynamic Therapy of Periapical Periodontitis - PubMed

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Periapical periodontitis (AP) is an inflammatory disease caused by persistent endodontic biofilms, challenging to treat with conventional root canal therapy.
A multifunctional bimetallic ion-modified metal-organic framework (MOF) nanozyme composite, MOF-FeAg-AMP@HA, was developed for synergistic AP therapy.
The nanozyme exhibits pH-responsive dual enzymatic activities: peroxidase (POD)-like activity under acidic conditions for bactericidal effects and superoxide dismutase (SOD)-like activity under neutral conditions to scavenge ROS.
Surface functionalization with antimicrobial peptide LL-37 enhances bacterial membrane disruption, and a hyaluronic acid (HA) coating improves biocompatibility and stability.
The nanocomposite shows potent broad-spectrum antibacterial activity, eradicates bacterial biofilms in vitro, and promotes tissue repair by stimulating endothelial cell migration and angiogenesis.
In vivo studies using a rat AP model demonstrated suppression of alveolar bone resorption by blocking the NF-κB/HIF-1α/NLRP3 signaling axis to inhibit pyroptosis.
The nanocomposite induces macrophage polarization toward the anti-inflammatory M2 phenotype, aiding in microenvironment reprogramming for bone regeneration.

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