Magnetoelectric Coupling Stimulation Modulates Macrophage Reprogramming for Superior Infected Periodontal Tissue Regeneration

ABSTRACT Clinical management of periodontitis requires addressing both bacterial infection and the deficient osteogenic microenvironment to optimize tissue regeneration. Electroactive biomaterials have demonstrated promise in bone regeneration, but are insufficient to enduringly synergize antibacterial properties with optimal immunomodulatory and tissue remodeling effects within the complex inflammatory microenvironment. Here, this study proposes an efficient, dynamic magnetoelectric conversion‐based therapeutic strategy, which integrates antibacterial activity and immunomodulation to optimize periodontal tissue regeneration. Magnetic field‐sensitive CoFe 2 O 4 ‐BiFeO 3 nanoparticles (CFO‐BFO NPs) are developed as a pioneering magnetoelectric biomaterial for periodontitis therapy. Magnetoelectric CFO‐BFO NPs significantly enhance osteogenesis of periodontal ligament stem cells (PDLSCs) and exhibit potent antibacterial activity in vitro. Crucially, magnetoelectric coupling stimulation can program macrophage from the M1 to M2 phenotype via the PI3K‐Akt signaling pathway, thereby enhancing osteogenesis. Moreover, magnetoelectric CFO‐BFO NPs can also alleviate tissue inflammation and accelerate infected periodontal bone regeneration in Porphyromonas gingivalis ( P. gingivalis )‐mediated periodontitis mice models. After 4 weeks of treatment, the bone volume fraction (BV/TV) in the magnetoelectric CFO‐BFO NPs group approached healthy levels. This study pioneers the application of magnetoelectric coupling materials for periodontitis treatment and provides a novel strategy for enhancing the therapeutic effects of electroactive biomaterials on periodontitis.