Remodeling Microenvironment for Implant‐Associated Osteomyelitis by Dual Metal Peroxide

Abstract Implant‐associated osteomyelitis (IAOM) is characterized by bone infection and destruction; current therapy of antibiotic treatment and surgical debridement often results in drug resistance and bone defect. It is challenging to develop an antibiotic‐free bactericidal and osteogenic‐enhanced strategy for IAOM. Herein, an IAOM‐tailored antibacterial and osteoinductive composite of copper (Cu)–strontium (Sr) peroxide nanoparticles (CSp NPs), encapsulated in polyethylene glycol diacrylate (PEGDA) (CSp@PEGDA), is designed. The dual functional CSp NPs display hydrogen peroxide (H 2 O 2 ) self‐supplying and Fenton catalytic Cu 2+ ions’ release, generating plenty of hydroxyl radical ( • OH) in a pH‐responsive manner for bacterial killing, while the released Sr 2+ promotes the in vitro osteogenicity regarding cell proliferation, alkaline phosphatase activity, extracellular matrix calcification, and osteo‐associated genes expression. The integration of Cu 2+ and Sr 2+ in CSp NPs together with the coated PEGDA hydrogel ensures the stable and sustainable ion release during short‐ and long‐term periods. Benefitted from the injectablity and photo‐crosslink ability, CSp@PEGDA is able to thoroughly fill the infectious site and gelate in situ for bacterial elimination and bone regeneration, which is verified through in vivo evaluation using a clinical‐simulating IAOM mouse model. These favorable abilities of CSp@PEGDA precisely meet the multiple therapeutic needs and pave a promising way for implant‐associated osteomyelitis treatment.