Tailored regulation of ferroptosis in periodontitis using thermosensitive ionic liquid hydrogel based on galangin/L-cysteine-decorated MoS2 nanoflowers

Periodontitis is a chronic inflammatory disease, driven by excessive pathogenic bacteria, characterized by severe inflammatory response and periodontal tissue damage. Recent research underscores the involvement of ferroptosis in periodontitis progression. However, due to the multifactorial mechanism underlying ferroptosis, the traditional drug intervention strategy focusing on a single target have been unable to solve all the harmful factors and achieve complete clinical cure. Herein, a multifunctional MoS₂ nanoflowers was developed by decorating L-cysteine and galangin (MLG), while incorporate in a thermosensitive ionic liquid hydrogel (ACIS@MLG), which offer multitarget tailored regulation of ferroptosis. The characteristics of ACIS@MLG was evaluated, and their therapeutic effects on pathogens and LPS-induced periodontitis rat model were verified. ACIS@MLG performed excellent antibacterial, anti-inflammatory and protective effects on periodontal tissue. Mechanistically, transcriptomics analyses suggested that MLG exerted therapeutic effects by regulating ferroptosis in periodontal ligament stem cells. MLG restored ferroptosis-induced mitochondrial membrane potential abnormalities through ROS scavenging and reducing iron overload. In addition, MLG inhibited ferroptosis by remodeling lipid peroxidation via AMPK/Nrf2/SLC7A11 pathway. Overall, this multifunctional nanozyme composite hydrogel offers a tailored ferroptosis regulation strategy for periodontitis treatment.