ROS-Balancing-Engineered Bio-Heterojunction Hydrogel Accelerated the Infected Bone Regeneration Based on Sono-Chemo Dynamic Therapy

Objectives: Hypoxic deep-seated infections in refractory environments impede healing and exacerbate antibiotic resistance. Sonodynamic therapy (SDT) shows promise in combating pathogenic bacteria; however, excessive reactive oxygen species (ROS) generated during the process often lead to severe inflammatory responses, hindering tissue regeneration.
Methods: To address these limitations, we have developed a multifunctional MXene-TiO₂ bio-heterojunction (bioHJs) hydrogel that employs ultrasound-triggered dynamic ROS modulation for spatiotemporally controlled antibacterial therapy and enhanced tissue regeneration
Results: This approach effectively addresses the dual challenges of infection management and oxidative stress. Under ultrasound stimulation, MXene-TiO₂ bioHJs rapidly eradicate bacteria by disrupting membrane structures and electron transport chains (ETCs) while generating substantial ROS. Once the ultrasound ceases, the hydrogel and its degradation products neutralize residual ROS produced during sonodynamic therapy (SDT). In vivo studies further demonstrate that the nanohydrogel accelerates soft tissue regeneration and periodontal bone regeneration by eradicating bacterial biofilms, activating the TGF-β/SMAD signaling pathway, and promoting angiogenesis.
Conclusions: This work introduces a novel strategy for equipping hydrogels with programmed antibacterial and anti-inflammatory capabilities, providing an innovative solution for treating deep-seated infections, particularly in periodontal therapy.