Disorder-Engineered Thermoelectric Cu2Se/SnSe2 Heterojunctions Embedded in Glycyrrhizic Acid Hydrogels for Pyro-Photo-Ultrasonic Therapy of Periodontitis.

Periodontitis treatment is severely hampered by rapid electron-hole recombination and hypoxic microenvironment, which fundamentally limit reactive oxygen species (ROS) yields in conventional photo/sonodynamic therapies. Herein, we propose a disorder-engineered thermoelectric heterojunction strategy that couples pyro-photo-ultrasonic effects to overcome these bottlenecks. Thermoelectric Cu2Se(CuSe)/SnSe2 heterojunctions, synthesized by mechanochemical ball milling, introduce dense CuSe nanodomains and interfacial defects that serve simultaneously as phonon-scattering centers (minimizing thermal conductivity of κtot = 0.09 W/(m·K)) and non-radiative relaxation channels, enabling efficient photo-to-thermal conversion. A pronounced built-in electric field, arising from the large work function difference between Cu2Se (7.17 eV) and SnSe2 (6.52 eV), synergizes with the thermoelectric field induced by photo-ultrasonic thermal gradients, yielding sustained carrier separation (ZT = 0.08 at 450 K) and robust ROS generation under hypoxic conditions. The resultant heterojunction achieves unprecedented antibacterial efficacy (>98.37% against Staphylococcus aureus and >99.54% against Porphyromonas gingivalis) under 808 nm NIR/ultrasound co-activation. Integration of glycyrrhizic acid hydrogel provides a biocompatible matrix (97.8% cell viability, <5% hemolysis) that substantially downregulates TNF-α, reduces osteoclastogenesis significantly, and markedly restores alveolar bone height. This work establishes a "disorder-engineering for biocatalysis" strategy, demonstrating that controllable lattice imperfections can be harnessed to drive multi-physical coupling for high-efficacy therapy of infected bone tissues. STATEMENT OF SIGNIFICANCE: Conventional mechanical/antibiotic treatment and prevailing exogenous stimulus-responsive strategies face significant problems in the treatment of periodontitis, mainly in rising bacterial resistance, insufficient deep pathogen elimination and limited antibacterial ability. In this work, we constructed a Cu2Se(CuSe)/SnSe2 thermoelectric heterojunction based on disorder-engineering strategy. Under near-infrared and ultrasonic co-stimulation, the synergy between built-in electric field and thermoelectromotive force effectively suppresses carrier recombination, enabling remarkably enhanced ROS generation and bactericidal efficacy under periodontal hypoxic microenvironment. Integrated with glycyrrhizic acid hydrogel, the system achieves favorable biocompatibility, anti-inflammatory activity, and alveolar bone repair capacity, offering a meaningful paradigm for multi-physical field synergistic antibacterial therapy.