Initial therapeutic evidence of a borosilicate bioactive glass (BSG) and Fe 3 O 4 magnetic nanoparticle scaffold on implant-associated Staphylococcal
作者全名：Jin, Ying; Liu, Hang; Chu, Lei; Yang, Jin; Li, Xiuyang; Zhou, Hang; Jiang, Haitao; Shi, Lei; Weeks, Jason; Rainbolt, Joshua; Yang, Changjiang; Xue, Thomas; Pan, Haobo; Deng, Zhongliang; Xie, Chao; Cui, Xu; Ren, Youliang
作者地址：[Jin, Ying; Liu, Hang; Chu, Lei; Li, Xiuyang; Zhou, Hang; Jiang, Haitao; Shi, Lei; Deng, Zhongliang; Ren, Youliang] Chongqing Med Univ, Affiliated Hosp 2, Dept Orthopaed, 76 Linjiang Rd, Chongqing 400010, Peoples R China; [Yang, Jin] Zunyi Med Univ, Dept Orthopaed, Zunyi, Guizhou, Peoples R China; [Li, Xiuyang; Pan, Haobo] Chongqing Univ Technol, Peoples Hosp Chongqing 7, Cent Hosp Affiliated, Dept Orthoped, Chongqing 400054, Peoples R China; [Weeks, Jason; Rainbolt, Joshua; Xue, Thomas; Xie, Chao] Univ Rochester, Ctr Musculoskeletal Res, Dept Orthopaed & Phys Performance Ctr, Med Ctr, Rochester, NY 14642 USA; [Cui, Xu] Chinese Acad Sci, Shenzhen Inst Adv Technol, Shenzhen Key Lab Marine Biomed Mat, Key Lab Biomed Imaging Sci & Syst,CAS HK Joint Lab, Shenzhen 518055, Peoples R China
通信作者：Ren, YL (通讯作者)，Chongqing Med Univ, Affiliated Hosp 2, Dept Orthopaed, 76 Linjiang Rd, Chongqing 400010, Peoples R China.; Cui, X (通讯作者)，Chinese Acad Sci, Shenzhen Inst Adv Technol, Shenzhen Key Lab Marine Biomed Mat, Key Lab Biomed Imaging Sci & Syst,CAS HK Joint Lab, Shenzhen 518055, Peoples R China.
来源：BIOACTIVE MATERIALS
ESI学科分类：
WOS号：WOS:001249319400001
JCR分区：Q1
影响因子：18
年份：2024
卷号：40
期号：
开始页：148
结束页：167
文献类型：Article
关键词：Osteomyelitis; Staphylococcus aureus; Biofilm; Borosilicate bioactive glass; Magnetic nanoparticles
摘要：Implant -associated Staphylococcus aureus ( S. aureus ) osteomyelitis is a severe challenge in orthopedics. While antibiotic -loaded bone cement is a standardized therapeutic approach for S. aureus osteomyelitis, it falls short in eradicating Staphylococcus abscess communities (SACs) and bacteria within osteocyte-lacuna canalicular network (OLCN) and repairing bone defects. To address limitations, we developed a borosilicate bioactive glass (BSG) combined with ferroferric oxide (Fe 3 O 4 ) magnetic scaffold to enhance antibacterial efficacy and bone repair capabilities. We conducted comprehensive assessments of the osteoinductive, immunomodulatory, antibacterial properties, and thermal response of this scaffold, with or without an alternating magnetic field (AMF). Utilizing a well -established implant -related S. aureus tibial infection rabbit model, we evaluated its antibacterial performance in vivo . RNA transcriptome sequencing demonstrated that BSG + 5%Fe 3 O 4 enhanced the immune response to bacteria and promoted osteogenic differentiation and mineralization of MSCs. Notably, BSG + 5% Fe 3 O 4 upregulated gene expression of NOD -like receptor and TNF pathway in MSCs, alongside increased the expression of osteogenic factors (RUNX2, ALP and OCN) in vitro . Flow cytometry on macrophage exhibited a polarization effect towards M2, accompanied by upregulation of anti-inflammatory genes (TGF-81 and IL-1Ra) and downregulation of pro -inflammatory genes (IL -6 and IL -18) among macrophages. In vivo CT imaging revealed the absence of osteolysis and periosteal response in rabbits treated with BSG + 5%Fe 3 O 4 + AMF at 42 days. Histological analysis indicated complete controls of SACs and bacteria within OLCN by day 42, along with new bone formation, signifying effective control of S. aureus osteomyelitis. Further investigations will focus on the in vivo biosafety and biological mechanism of this scaffold within infectious microenvironment.
基金机构：National Key R & D Program of China [2023YFC2416900, 2021YFC2400500]; International Postdoctoral Exchange Fellowship Program of Chongqing [2021JLPY004]; Fellowship of China Postdoctoral Science Foundation [2021M693758]; National Natural Science Foundation of China [U22A20357, 52072398, 32161160327]; Natural Science Foundation Postdoctoral Science Foundation Project of Chongqing [cstc2021jcyj-bsh0019]; Natural Science Foundation of Chongqing [cstc2021jcyj-msxmX0134]; Shenzhen Science and Technology Program [JCYJ20230807140714030]
基金资助正文：The authors acknowledge the support from National Key R & D Program of China (2023YFC2416900 and 2021YFC2400500), The International Postdoctoral Exchange Fellowship Program of Chongqing (2021JLPY004), The Fellowship of China Postdoctoral Science Foundation (2021M693758), National Natural Science Foundation of China (U22A20357, 52072398and 32161160327), Natural Science Foundation Postdoctoral Science Foundation Project of Chongqing (cstc2021jcyj-bsh0019), Natural Science Foundation of Chongqing (cstc2021jcyj-msxmX0134), Shenzhen Science and Technology Program (JCYJ20230807140714030). Thanks to the Chongqing Key Laboratory of Ultrasound Molecular Imaging, The Key Laboratory of Biochemistry and Molecular Pharmacology of Chongqing, Key Laboratory of Laboratory Medical Diagnostics Ministry of Education. In addition, We would like to thank the Imaging Department of the Second Affiliated Hospital of Chongqing Medical University for the help of CT scanning, We would like to thank Professor Pan/Dr. Cui's research groups (Shenzhen Institute of Advanced Technology, Chinese Academy of Science) for assistance with the experimental technology.
