An Intelligent MXene Nanoplatform for Bone Regeneration in Periodontitis Through Synergistic Scavenging Pathogenic...

Area of Science:

• Biomaterials Science
• Nanomedicine
• Regenerative Medicine

Background:

• Periodontitis is a complex inflammatory disease with limited regenerative treatment options.
• Bacterial dysbiosis and oxidative stress are key drivers of periodontitis pathogenesis.
• Current therapies struggle to address the multifactorial nature of periodontal disease.

Purpose of the Study:

• To engineer an intelligent pH-responsive MXene-based nanosystem (MPDM) for periodontitis treatment.
• To integrate cfDNA capture, osteogenic reprogramming, and targeted delivery functionalities into a single therapeutic platform.
• To evaluate the efficacy of MPDM in vitro and in a murine periodontitis model.

Main Methods:

• Development of a pH-responsive MXene-based nanosystem (MPDM) incorporating polyethyleneimine (PEI), methyltransferase-like 3/14 (METTL3/14), and 2,3-dimethylmaleic anhydride (DMMA).
• In vitro assessment of antibacterial activity, reactive oxygen species (ROS) scavenging, and inflammation-triggered release.
• In vivo evaluation using a murine ligature-induced periodontitis model with micro-CT and transcriptomic analysis.

Main Results:

• MPDM demonstrated synergistic antibacterial effects, potent ROS scavenging, and controlled payload release in inflammatory conditions.
• In vivo studies showed MPDM significantly reduced alveolar bone loss, increasing bone volume fraction by 32%.
• Transcriptomic analysis revealed MPDM downregulated TLR and NET signaling pathways and suppressed osteoclast differentiation.

Conclusions:

• The engineered MPDM nanosystem offers a promising therapeutic strategy for periodontitis by neutralizing pathogenic triggers and promoting bone regeneration.
• This work establishes a novel nanotherapeutic framework for inflammatory bone disorders.
• The developed platform holds potential applicability for other multifactorial diseases.