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Vancomycin- and Strontium-Loaded Microspheres with Multifunctional Activities against Bacteria, in Angiogenesis, and in Osteogenesis for Enhancing Infected Bone Regeneration

  • Pengfei Wei
    Pengfei Wei
    State Key Laboratory of Organic−Inorganic Composites, Beijing Laboratory of Biomedical Materials, Beijing University of Chemical Technology, Beijing 100029, P. R. China
    More by Pengfei Wei
  • Wei Jing
    Wei Jing
    State Key Laboratory of Organic−Inorganic Composites, Beijing Laboratory of Biomedical Materials, Beijing University of Chemical Technology, Beijing 100029, P. R. China
    More by Wei Jing
  • Zuoying Yuan
    Zuoying Yuan
    State Key Laboratory of Organic−Inorganic Composites, Beijing Laboratory of Biomedical Materials, Beijing University of Chemical Technology, Beijing 100029, P. R. China
    More by Zuoying Yuan
  • Yiqian Huang
    Yiqian Huang
    State Key Laboratory of Organic−Inorganic Composites, Beijing Laboratory of Biomedical Materials, Beijing University of Chemical Technology, Beijing 100029, P. R. China
    More by Yiqian Huang
  • Binbin Guan
    Binbin Guan
    Department of Stomatology, Tianjin Medical University General Hospital, Tianjin 300052, P. R. China
    More by Binbin Guan
  • Wenxin Zhang
    Wenxin Zhang
    Department of Endodontics, School and Hospital of Stomatology, Tianjin Medical University, Tianjin 300070, P. R. China
    More by Wenxin Zhang
  • Xu Zhang
    Xu Zhang
    Department of Endodontics, School and Hospital of Stomatology, Tianjin Medical University, Tianjin 300070, P. R. China
    More by Xu Zhang
  • Jianping Mao
    Jianping Mao
    Department of Spine Surgery, Beijing Jishuitan Hospital, Beijing 100035, P. R. China
    More by Jianping Mao
  • Qing Cai*
    Qing Cai
    State Key Laboratory of Organic−Inorganic Composites, Beijing Laboratory of Biomedical Materials, Beijing University of Chemical Technology, Beijing 100029, P. R. China
    *E-mail: [email protected] (Q.C.).
    More by Qing Cai
  • Dafu Chen*
    Dafu Chen
    Laboratory of Bone Tissue Engineering, Beijing Research Institute of Traumatology and Orthopaedics, Beijing Jishuitan Hospital, Beijing 100035, P. R. China
    *E-mail: [email protected] (D.C.).
    More by Dafu Chen
  • , and 
  • Xiaoping Yang
    Xiaoping Yang
    State Key Laboratory of Organic−Inorganic Composites, Beijing Laboratory of Biomedical Materials, Beijing University of Chemical Technology, Beijing 100029, P. R. China
Cite this: ACS Appl. Mater. Interfaces 2019, 11, 34, 30596–30609
Publication Date (Web):August 2, 2019
https://doi.org/10.1021/acsami.9b10219
Copyright © 2019 American Chemical Society
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Abstract

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Biomaterials that have capacities to simultaneously induce bone regeneration and kill bacteria are in demand because bone defects face risks of severe infection in clinical therapy. To meet the demand, multifunctional biodegradable microspheres are fabricated, which contain vancomycin to provide antibacterial activity and strontium-doped apatite to provide osteocompatibility. Moreover, the strontium component shows activity in promoting angiogenesis, which further favors osteogenesis. For producing the microspheres, vancomycin is loaded into mesoporous silica and embedded in polylactide-based microspheres via the double emulsion technique and the strontium-doped apatite is deposited onto the microspheres via biomineralization in strontium-containing simulated body fluid. Sustained release behaviors of both vancomycin and Sr2+ ions are achieved. The microspheres exhibit strong antibacterial effect against Staphylococcus aureus, while demonstrating excellent cell/tissue compatibility. Studies of differentiation confirm that the introduction of strontium element strengthens the angiogenic and osteogenic expressions of mesenchymal stromal cells. Subcutaneous injection of the microspheres into rabbit’s back confirms their effectiveness in inducing neovascularization and ectopic osteogenesis. Finally, an infected rabbit femoral condyle defect model is created with S. aureus infection and the multifunctional microspheres are injected, which display significant antibacterial activity in vivo and achieve efficient new bone formation in comparison with biomineralized microspheres without vancomycin loading. The vancomycin- and strontium-loaded microspheres, being biomineralized, injectable, and biodegradable, are attractive because of their flexibility in integrating multiple functions into one design, whose potentials in treating infected bone defects are highly expected.

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The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acsami.9b10219.

  • Schematic process of generating infected bone defects, characterizations of MCF-26-type MSN, particle sizes of prepared microspheres, characterizations of biomineralized microspheres, cell proliferation in the presence of microspheres, macroscopic observation on subcutaneously implanted microspheres, HE staining on rat liver and kidney sections, ectopic osteogenesis, micro-CT on infected defects, and primers for various genes (PDF)

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Cited By


This article is cited by 3 publications.

  1. Yiqian Huang, Zhiyun Du, Pengfei Wei, Fuyu Chen, Binbin Guan, Zhenda Zhao, Xu Zhang, Qing Cai, Jianping Mao, Huijie Leng, Xiaoping Yang. Biodegradable microspheres made of conductive polyorganophosphazene showing antioxidant capacity for improved bone regeneration. Chemical Engineering Journal 2020, 397 , 125352. https://doi.org/10.1016/j.cej.2020.125352
  2. Zuoying Yuan, Zhuo Wan, Pengfei Wei, Xin Lu, Jianping Mao, Qing Cai, Xu Zhang, Xiaoping Yang. Dual‐Controlled Release of Icariin/Mg 2+ from Biodegradable Microspheres and Their Synergistic Upregulation Effect on Bone Regeneration. Advanced Healthcare Materials 2020, 2014 , 2000211. https://doi.org/10.1002/adhm.202000211
  3. Qianmin Ou, Keqing Huang, Chuanqiang Fu, Chunlin Huang, Yifei Fang, Zhipeng Gu, Jun Wu, Yan Wang. Nanosilver-incorporated halloysite nanotubes/gelatin methacrylate hybrid hydrogel with osteoimmunomodulatory and antibacterial activity for bone regeneration. Chemical Engineering Journal 2020, 382 , 123019. https://doi.org/10.1016/j.cej.2019.123019

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