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Fe3O4 magnetic nanoparticles provide a novel alternative strategy for Staphylococcus aureus bone infection

  • Youliang, Ren (Department of Orthopaedics, Second Affiliated Hospital of Chongqing Medical University) ;
  • Jin, Yang (Department of Orthopaedics, Second Affiliated Hospital of Chongqing Medical University) ;
  • Jinghui, Zhang (Key Laboratory of Diagnostic Medicine designated by the Ministry of Education, Department of Laboratory Medicine, Chongqing Medical University Chongqing) ;
  • Xiao, Yang (Department of Orthopaedics, Second Affiliated Hospital of Chongqing Medical University) ;
  • Lei, Shi (Department of Orthopaedics, Second Affiliated Hospital of Chongqing Medical University) ;
  • Dajing, Guo (Department of Radiology, The Second Affiliated Hospital of Chongqing Medical University) ;
  • Yuanyi, Zheng (Shanghai Institute of Ultrasound in Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital) ;
  • Haitao, Ran (Chongqing Key Laboratory of Ultrasound Molecular Imaging, Second Affiliated Hospital of Chongqing Medical University) ;
  • Zhongliang, Deng (Department of Orthopaedics, Second Affiliated Hospital of Chongqing Medical University) ;
  • Lei, Chu (Department of Orthopaedics, Second Affiliated Hospital of Chongqing Medical University)
  • Received : 2021.12.14
  • Accepted : 2022.06.17
  • Published : 2022.12.25
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Abstract

Due to its biofilm formation and colonization of the osteocyte-lacuno canalicular network (OLCN), Staphylococcus aureus (S.aureus) implant-associated bone infection (SIABI) is difficult to cure thoroughly, and may occur recurrently subsequently after a long period dormant. It is essential to explore an alternative therapeutic strategy that can eradicate the pathogens in the infected foci. To address this, the polymethylmethacrylate (PMMA) bone cement and Fe3O4 nanoparticles compound cylinder were developed as implants based on their size and mechanical properties for the alternative magnetic field (AMF) induced thermal ablation, The PMMA mixed with optimized 2% Fe3O4 nanoparticles showed an excellent antibacterial efficacy in vitro. It was evaluated by the CFU, CT scan and histopathological staining on a rabbit 1-stage transtibial screw model. The results showed that on week 7, the CFU of infected soft tissue and implants, and the white blood cells (WBCs) of the PMMA+2% Fe3O4+AMF group decreased significantly from their controls (p<0.05). PMMA+2% Fe3O4+AMF group did not observe bone resorption, periosteal reaction, and infectious reactive bone formation by CT images. Further histopathological H&E and Gram Staining confirmed there was no obvious inflammatory cell infiltration, neither pathogens residue nor noticeably burn damage around the infected screw channel in the PMMA+2% Fe3O4+AMF group. Further investigation of nanoparticle distributions in bone marrow medullary and vital organs of heart, liver, spleen, lung, and kidney. There were no significantly extra Fe3O4 nanoparticles were observed in the medullary cavity and all vital organs either. In the current study, PMMA+2% Fe3O4+AMF shows promising therapeutic potential for SIABI by providing excellent mechanical support, and promising efficacy of eradicating the residual pathogenic bacteria in bone infected lesions.

Keywords

Acknowledgement

Dr.Youliang Ren and Dr. Jin Yang contributed equally to this article as the co-first author. This work was supported by the Fellowship of China Postdoctoral Science Foundation (2021M693758) and Natural Science Foundation Postdoctoral Science Foundation Project of Chongqing (cstc2021jcyj-bsh0019). We are grateful to acknowledge Thomas Xue (University of Rochester, Rochester, USA) for proofreading this manuscript. Dr. Jing Zhang (Department of Hematology, Shanghai Tongren Hospital) for assistance with statistical analysis.

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