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

具有连续活性氧调节功能的可生物降解 Janus 声酶,用于治疗感染的临界尺寸骨缺损

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作者: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

Abstract

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.

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