Ultrasound-activated piezoelectric heterojunction drives nanozyme catalysis to induce bacterial cuproptosis-like death and promote bone vascularization and osseointegration

Abstract

Osteomyelitis is a severe and persistent bone infection that poses significant challenges to clinical treatment, often requiring prolonged antibiotic therapy and invasive procedures. Nanomaterial-based non-antibiotic therapies have emerged as promising alternatives in combating bacterial infections. However, effectively treating osteomyelitis while simultaneously promoting bone repair remains a challenge. Herein, we developed a nanoheterojunction catalytic reactor composed of copper ferrite (CuFe₂O₄) and molybdenum disulfide (MoS₂) quantum dots (CFO@MoS₂), leveraging ultrasound catalysis in combination with copper ions to induce bacterial cuproptosis-like death. Theoretical calculations indicate that the establishment of a heterojunction interface can accelerate oxygen adsorption, inducing electron flow toward oxygen atoms at the interface, thereby enhancing the separation of interface electron-hole pairs. Furthermore, copper ions released from CFO@MoS₂ undergo valence state changes under ultrasound, activating the Fenton reaction and releasing reactive oxygen species to kill bacteria. Gene sequencing shows that CFO@MoS₂, when activated by ultrasound, disrupts bacterial energy synthesis, interferes with bacterial metabolism, and induces copper-related bacterial death. More importantly, the microcurrents generated by ultrasound synergistic with the released copper and iron ions stimulate the expression of angiogenic and osteogenic genes, promoting bone regeneration. The ultrasound-triggered catalytic reaction by CFO@MoS₂ disrupts bacterial homeostasis, accelerates bacterial death, and offers a novel therapeutic strategy for osteomyelitis.