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<p>Osteomyelitis is a refractory bacterial infection of bone, presenting significant clinical management challenges due to its limited therapeutic outcome. Here, we developed heterojunction-structured sub-1&#xa0;nm copper oxide-decorated strontium titanate nanosheets (Cu-STO NSs), which integrate piezocatalytic reactive oxygen species (ROS) generation with augmented copper-induced bacterial death for synergistic osteomyelitis treatment. Under ultrasound (US) irradiation, the oxygen vacancies and heterojunction structure of Cu-STO NSs facilitate the separation of piezo-generated electron–hole pairs while reducing energy barriers, thereby enhancing ROS generation. This process is augmented by the US-accelerated Cu<sup>2+</sup>/Cu<sup>+</sup> redox cycling, which enables sustained hydroxyl radicals supply via Fenton-like reactions. The US-driven piezocatalytic action simultaneously enhances bacterial membrane permeability, facilitating intracellular copper overload and thereby triggering copper-induced metabolic toxicity in <i>Staphylococcus aureus</i> (<i>S. aureus</i>). Subsequent release of bioactive Cu and Sr ions from Cu-STO NSs significantly upregulates osteogenic differentiation of bone marrow stromal cells. In rat osteomyelitis, Cu-STO NSs achieve efficient bacterial eradication while stimulating on-demand bone regeneration. This work thus presents a non-invasive, spatiotemporal controlled copper-induced bacterial death strategy that concurrently addresses antibacterial and osteogenic challenges in infected bone regeneration.</p> Graphical Abstract <p></p>

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Leveraging piezo-augmented copper-induced bacterial death of sub-1 nm CuO-SrTiO3-x heterojunction nanosheets for osteomyelitis eradication

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年4月15日

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  • Xueqing Wang,
  • Kai Li,
  • Wenyan Xu,
  • Danyang Wang,
  • Ying Wang,
  • Junkun Feng,
  • Yi Chen,
  • Xiaoyi Liu,
  • Zishan Xu,
  • Xiaojia Liu,
  • Shaohua Ge,
  • Hong Liu,
  • Jianhua Li

摘要

Osteomyelitis is a refractory bacterial infection of bone, presenting significant clinical management challenges due to its limited therapeutic outcome. Here, we developed heterojunction-structured sub-1 nm copper oxide-decorated strontium titanate nanosheets (Cu-STO NSs), which integrate piezocatalytic reactive oxygen species (ROS) generation with augmented copper-induced bacterial death for synergistic osteomyelitis treatment. Under ultrasound (US) irradiation, the oxygen vacancies and heterojunction structure of Cu-STO NSs facilitate the separation of piezo-generated electron–hole pairs while reducing energy barriers, thereby enhancing ROS generation. This process is augmented by the US-accelerated Cu2+/Cu+ redox cycling, which enables sustained hydroxyl radicals supply via Fenton-like reactions. The US-driven piezocatalytic action simultaneously enhances bacterial membrane permeability, facilitating intracellular copper overload and thereby triggering copper-induced metabolic toxicity in Staphylococcus aureus (S. aureus). Subsequent release of bioactive Cu and Sr ions from Cu-STO NSs significantly upregulates osteogenic differentiation of bone marrow stromal cells. In rat osteomyelitis, Cu-STO NSs achieve efficient bacterial eradication while stimulating on-demand bone regeneration. This work thus presents a non-invasive, spatiotemporal controlled copper-induced bacterial death strategy that concurrently addresses antibacterial and osteogenic challenges in infected bone regeneration.

Graphical Abstract