Hierarchically Targeting and ROS-Responsive Platform for Diabetic Periodontitis Treatment through Mitochondrial...

Area of Science:

• Biomaterials Science
• Nanotechnology
• Periodontology

Background:

• Diabetic periodontitis involves persistent inflammation driven by reactive oxygen species (ROS) and mitochondrial dysfunction in M1 macrophages.
• A vicious cycle of ROS exacerbates inflammation and osteogenic impairment in diabetic periodontitis.

Purpose of the Study:

• To develop a hierarchically targeted, ROS-responsive nanoparticle-hydrogel platform for treating diabetic periodontitis.
• To disrupt the ROS vicious loop in M1 macrophages and restore mitochondrial function.

Main Methods:

• Engineered polymeric nanoparticles (MPPT NPs) with tuftsin peptide for M1 macrophage targeting and mitoquinone mesylate (MitoQ) for mitochondrial repair.
• Incorporated MPPT NPs into a ROS-responsive hydrogel (MTP hydrogel) using a ROS-cleavable linker (TSPBA).
• Evaluated the platform's efficacy in vitro and in a diabetic periodontitis rat model.

Main Results:

• MPPT NPs repaired oxidatively damaged mitochondria and suppressed NLRP3 inflammasome activation in vitro.
• MTP hydrogel reduced pro-inflammatory cytokine release and prevented inflammation-induced osteogenic impairment.
• Local MTP hydrogel administration in rats significantly reduced periodontal tissue destruction and enhanced alveolar bone regeneration.

Conclusions:

• The developed MTP hydrogel platform effectively disrupts the ROS vicious loop in M1 macrophages.
• This hierarchical, ROS-responsive system offers a promising therapeutic strategy for diabetic periodontitis management.
• The platform demonstrated significant periodontal tissue repair and alveolar bone regeneration capabilities.