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

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-Fe₂O₃ 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 Fe₂O₃-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.