Remodeling Microenvironment for Implant‐Associated Osteomyelitis by Dual Metal Peroxide

Author:

Guan Xin1,Wu Siyuan1,Ouyang Sixue2,Ren Shuchen1,Cui Naiqian1,Wu Xiaohu3,Xiang Dayong4,Chen Wenting5,Yu Bin14,Zhao Peng6,Wang Bowei14ORCID

Affiliation:

1. Guangdong Provincial Key Laboratory of Bone and Cartilage Regenerative Medicine Nanfang Hospital Southern Medical University Guangzhou 510515 China

2. School of Chemistry and Chemical Engineering South China University of Technology Guangzhou 510640 China

3. Department of Orthopedics Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences) Southern Medical University Guangzhou 510515 China

4. Division of Orthopaedic Trauma Department of Orthopaedics, Nanfang Hospital Southern Medical University Guangzhou 510515 China

5. Department of Anesthesiology Nanfang Hospital Southern Medical University Guangzhou 510515 China

6. NMPA Key Laboratory for Research and Evaluation of Drug Metabolism Guangdong Provincial Key Laboratory of New Drug Screening School of Pharmaceutical Sciences Southern Medical University Guangzhou 510515 China

Abstract

AbstractImplant‐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.

Funder

National Natural Science Foundation of China

Natural Science Foundation of Guangdong Province

Publisher

Wiley

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