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

• Published in: Nature communications 2024-12, Vol.15 (1), p.10525-23
• Main Authors: Ou, Zixuan, Wei, Junyu, Lei, Jie, Wu, Di, Tong, Bide, Liang, Huaizhen, Zhu, Dingchao, Wang, Hongchuan, Zhou, Xingyu, Xu, Hanpeng, Du, Zhi, Du, Yifan, Tan, Lei, Yang, Cao, Feng, Xiaobo
• Format: Article
• Language: English
• Subjects: 13; 13/1; 13/31; 13/51; 14; 14/1; 14/19; 14/28; 14/3; 14/63; 147/28; 38; 38/77; 38/91; 631/1647/350/2093; 631/61/2035; 631/61/54/990; 82/1; 82/51; 82/80; Angiogenesis; Animals; Anti-Bacterial Agents - pharmacology; Anti-Bacterial Agents - therapeutic use; Antimicrobial activity; Antioxidants - metabolism; Antioxidants - pharmacology; Bacteria; Bacterial diseases; Biocompatible Materials - chemistry; Biodegradability; Biodegradable materials; Biodegradation; Bone growth; Bone Regeneration - drug effects; Catalase; Charge transfer; Chelation; Continuity (mathematics); Defects; Degradation; Humanities and Social Sciences; Inflammation; Long bone; Male; Mice; Modulation; multidisciplinary; Nonunion; Osteogenesis - drug effects; Quercetin; Quercetin - chemistry; Quercetin - pharmacology; Rats; Rats, Sprague-Dawley; Reactive oxygen species; Reactive Oxygen Species - metabolism; Regeneration; Regeneration (physiology); Science; Science (multidisciplinary); Skull; Skull - diagnostic imaging; Skull - metabolism; Superoxide dismutase
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-024-54894-8

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 MnN 4 and Cu 2 O 8 . 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.