Remodeling Microenvironment for Implant-Associated Osteomyelitis by Dual Metal Peroxide

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 (H2O2) self-supplying and Fenton catalytic Cu2+ ions' release, generating plenty of hydroxyl radical (center dot OH) in a pH-responsive manner for bacterial killing, while the released Sr2+ promotes the in vitro osteogenicity regarding cell proliferation, alkaline phosphatase activity, extracellular matrix calcification, and osteo-associated genes expression. The integration of Cu2+ and Sr2+ 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. Copper-strontium peroxide nanoparticle-loaded polyethylene glycol diacrylate (PEGDA) composites tailored for implant-associated osteomyelitis (IAOM) are constructed with outstanding antibacterial and osteoinductive capabilities in this study, which exhibit effective catalytic power for Fenton-like reaction and controllable ion release behavior. This research offers a novel and promising treatment strategy for IAOM. image