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

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 all time 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 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. In order to elucidate the mechanism by which MON(CuMn)-Q promotes osteogenesis, RNA sequencing was employed on hBMSCs. Two groups were established, comprising the control and MON(CuMn)-Q groups. The control group was maintained in a continuous culture of medium lacking any material for a period of 21 days, while the MON(CuMn)-Q group was subjected to a 21-day culture in a medium containing 150 µg/mL MON(CuMn)-Q. Following this, both groups underwent RNA sequencing.