A Novel Therapeutic Strategy For Osteomyelitis

Osteomyelitis is a deep tissue disease of destructive bone inflammation caused by microbial infection. And current treatments involve prolonged antibiotic therapy and invasive procedures. There is a critical need to develop a non-antibiotic, non-invasive and in situ strategy for eradicating osteomyelitis. In recent years, piezoelectric catalytic therapy has garnered significant attention due to its unique mechanical-to-electrical conversion properties, non-invasive nature, and deep tissue penetration capabilities. Herein, we developed a nanosheet composed of strontium titanate and copper nanoparticles, constructing a metal-nano heterojunction structure. This structure utilizes ultrasound-driven piezoelectric catalysis combined with copper ion-induced bacterial cuproptosis to treat osteomyelitis. The morphology of the prepared nanosheets and the establishment of the heterojunction interface enhance the separation of interfacial electron-hole pairs, thereby improving catalytic performance. Additionally, the copper ions released from the nanosheets undergo valence changes under ultrasound, activating Fenton-like reaction and releasing reactive oxygen species (ROS) to synergistically kill bacteria. Transcriptomic and metabolomic analyses revealed that intracellular copper overload restricts the tricarboxylic acid (TCA) cycle, triggering bacterial cuproptosis. Consequently, the ultrasound-triggered piezoelectric catalytic reaction of the nanosheets, in synergy with cuproptosis, disrupts bacterial homeostasis, accelerates bacterial death, and promotes on-demand bone formation in vivo. This provides a novel therapeutic strategy for osteomyelitis.