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Biodegradable Janus sonozyme with continuous reactive oxygen species regulation for treating infected critical-sized bone defects

  • Zixuan Ou,
  • Junyu Wei,
  • Jie Lei,
  • Di Wu,
  • Bide Tong,
  • Huaizhen Liang,
  • Dingchao Zhu,
  • Hongchuan Wang,
  • Xingyu Zhou,
  • Hanpeng Xu,
  • Zhi Du,
  • Yifan Du,
  • Lei Tan,
  • Cao Yang,
  • Xiaobo Feng

摘要

Critical-sized bone defects are usually accompanied by bacterial infection leading to inflammation and bone nonunion. However, existing biodegradable materials lack long-term therapeutical effect because of their gradual degradation. Here, a degradable material with continuous ROS modulation is proposed, defined as a sonozyme due to its functions as a sonosensitizer and a nanoenzyme. Before degradation, the sonozyme can exert an effective sonodynamic antimicrobial effect through the dual active sites of MnN4 and Cu2O8. Furthermore, it can promote anti-inflammation by superoxide dismutase- and catalase-like activities. Following degradation, quercetin-metal chelation exhibits a sustaining antioxidant effect through ligand-metal charge transfer, while the released ions and quercetin also have great self-antimicrobial, osteogenic, and angiogenic effects. A rat model of infected cranial defects demonstrates the sonozyme can rapidly eliminate bacteria and promote bone regeneration. This work presents a promising approach to engineer biodegradable materials with long-time effects for infectious bone defects.