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, Yang Cao, 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. Existing biodegradable materials lack long-term therapeutical effect because of their gradual degradation. Here, the authors develop a degradable material with continuous ROS modulation, which rapidly eliminates bacteria and promotes bone regeneration in infected cranial defects.