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 (H₂O₂) self-supplying and Fenton catalytic Cu²⁺ ions' release, generating plenty of hydroxyl radical (^•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.