MXene-based hydrogel disrupts bacterial biofilms and reprograms immune cell metabolism via photothermal-electron transfer effects to reverse bone resorption in periodontitis

Abstract Bacterial biofilm colonization and persistent chronic inflammation in periodontitis cause periodontal tissue destruction and eventual tooth loss. Bacterial biofilms disruption and immune cell metabolism reprogramming are critical for the treatment of periodontitis. Herein, we developed an injectable MXene-based hydrogel (GQM), composed of oxidized gellan gum, quaternized chitosan, and magnesium–tannic acid-modified MXene nanosheets (MTA-Mg), which serves as a flexible scaffold for targeted delivery of MTA-Mg within periodontal pockets. The GQM hydrogels can be injected into periodontal pockets and targetedly deliver MTA-Mg, which disrupts the dense biofilm efficiently by photothermal effect, while the bacteria are killed through the electrostatic interaction and charge neutralization from quaternized chitosan. MTA-Mg nanosheets serve as interfacial electron transfer to activate oxidative phosphorylation pathway, while delivering the magnesium and tannic acid to improve mitochondrial function, which reprogram the immune cell metabolism by inducing macrophage toward the M2 phenotype. The rat periodontitis model demonstrated that the GQM hydrogel effectively eradicates bacterial biofilms, alleviates inflammation, and reverses alveolar bone resorption, thereby treating periodontitis efficiently. All in all, the GQM hydrogel achieves a synergistic effect of "biofilm disruption–immune metabolic reprogramming" and offers a novel strategy for the reversal of inflammatory bone resorption in periodontitis.