A Multifunctional MXene‐Fe Composite Microneedle System for Phase‐Specific Periodontitis Therapy

Abstract The effective treatment of periodontitis is a major clinical challenge due to the difficulty of eradicating deep‐seated biofilms in periodontal pockets and coordinating subsequent tissue regeneration. Microneedles provide a minimally invasive transgingival delivery route that enables efficient drug administration to deep periodontal sites. Here, an innovative hyaluronic acid‐based microneedle system loaded with MXene‐Fe 2 O 3 nanocomposites (FM‐MN) has been developed to provide phase‐specific therapy for periodontitis. In the bacterial accumulation phase, near‐infrared (NIR) irradiation triggers synergistic antibacterial action through MXene‐mediated photothermal effects and Fe 2 O 3 ‐induced ferroptosis‐like bacterial death, eradicating biofilms at mild temperatures. In the tissue regeneration phase, the same system‐without irradiation‐ leverages the unique properties of MXene to scavenge reactive oxygen species, modulate inflammation, and promote osteogenic differentiation. RNA sequencing further reveals the underlying anti‐inflammatory and osteogenic mechanisms of this composite. In a rat periodontitis model, FM‐MN significantly reduces inflammation and restores alveolar bone. This work presents a dual‐action strategy for periodontitis but also offers a versatile microneedle‐based platform for other complex conditions requiring sequential treatment regimens.