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2015 Fiscal Year Annual Research Report

抗菌性と骨適合性の両方に優れる溶解性制御型Ag添加リン酸カルシウム膜の作製

Research Project

Project/Area Number 15J00660
Research InstitutionTohoku University

Principal Investigator

GOKCEKAYA OZKAN  東北大学, 工学研究科, 特別研究員(PD)

Project Period (FY) 2015-04-24 – 2017-03-31
Keywordssilver / incorporation / antibacterial / calcium phosphate / hydroxyapatite / tricalcium phosphate / cytotoxiciy / HRTEM
Outline of Annual Research Achievements

The effectiveness of Ag containing calcium phosphates was tested toward Gram-negative bacteria (E. coli). The antibacterial activity performance of Ag-incorporated β-tricalcium phosphate and metallic Ag coexisted hydroxyapatite were conducted with various exposure time and initial bacteria concentration. The results have shown that Ag-incorporated β-tricalcium phosphate was effective as an antibacterial material toward E. coli for even high initial bacteria concentration compared to metallic Ag coexisted hydroxyapatite without any toxicity. The mechanism of excellent antibacterial activity is based on Ag release through the continuous dissolution of Ag-incorporated β-tricalcium phosphate. The study of Ag-containing calcium phosphates has been focusing on hydroxyapatite for decades. However, we pointed out the effectiveness of Ag-incorporated β-tricalcium phosphate compared to metallic Ag coexisted hydroxyapatite. To our best knowledge, no reports have discussed the bioresorbability of Ag-incorporated β-TCP with respect to the incorporation amount of Ag and the β-tricalcium phosphate phase fraction. To clarify the atomic position of Ag in β-tricalcium phosphate and hydroxyapatite, I joined to Prof. Chen’s Laboratory in WPI-AIMR, Tohoku University for training for transmission electron microscopy (TEM) observations. The Ag atoms were detected in β-tricalcium phosphate by high angle annular dark field scanning transmission electron microscopy (HAADF-STEM). Ca(4) sites in β-TCP structure are occupied by Ag atoms.

Current Status of Research Progress
Current Status of Research Progress

1: Research has progressed more than it was originally planned.

Reason

The study of Ag-containing calcium phosphates has been focusing on hydroxyapatite for decades. However, this research showed the effectiveness of Ag-incorporated β-tricalcium phosphate for antibacterial applications. Furthermore, the study of atomic position of Ag atom in β-tricalcium phosphate structure is new information in this field, which gives an idea for the incorporation limit of the structure. The incorporation of Ag in β-tricalcium phosphate was occurred as an exchange of Ca(4) sites with Ag atoms. To clarify the position of Ag atoms in β-tricalcium phosphate structure, high angle annular dark field high resolution transmission electron microscopy (HAADF-STEM) is important technique due to the z contrast difference between Ca and Ag atoms. The atomic structure observations are ongoing. The skills for operating TEM machine are much improved by staying in Prof. Chen’s Laboratory for 6 months. Novel information on β-tricalcium phosphate structure is obtained as showing the incorporation of Ag into Ca(4) site for the first time by using a microscopic technique. In order to confirm the position of Ag atoms in β-tricalcium phosphate, STEM simulation study using software is going to be carried out. For detail explanation of Ag incorporation, HAADF-STEM observations are planned to conduct systematically with respect to the STEM simulations. The information of change in structural parameters and the limit of incorporation into calcium phosphates are valuable to understand the performance of bio-ceramics.

Strategy for Future Research Activity

The research is going to focus on coating techniques of Ag-containing calcium phosphate. The facilities we had in Prof. Narushima’s Laboratory allow us to fabricate coating by RF (radiofrequency) magnetron sputtering. I am going to focus on fabrication of Ag and other additional elements containing amorphous calcium phosphate coatings by RF magnetron sputtering. Additionally, the in vitro evaluations of these coatings are going to be conducted. Co-doping of Ag+other elements (Nb, Ta, etc.) to amorphous calcium phosphate coatings is considered to control bioresorbability and to enhance cell-compatibility. The effectiveness of Ag-incorporated amorphous calcium phosphate coatings is going to be tested toward Gram-negative (E. coli) and Gram-positive (S. aureus) bacteria. We evaluated antibacterial activity of Ag-incorporated β-tricalcium phosphate and metallic Ag coexisted hydroxyapatite with various exposure time and initial bacterial concentration. The results have shown that Ag-incorporated β-TCP was effective as an antibacterial material toward E. coli for even high initial bacteria concentration with a controlled and sustained release of Ag ions, superior comparing to metallic Ag coexisted hydroxyapatite. For amorphous calcium phosphate coatings, the research focus is on controlling the dissolution of amorphous calcium phosphate and sustained release of incorporated ions to obtain long-lasting antibacterial activity and biocompatibility. The coatings are going to be observed with HRTEM.

  • Research Products

    (9 results)

All 2016 2015

All Journal Article (4 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 4 results,  Acknowledgement Compliant: 2 results) Presentation (5 results) (of which Int'l Joint Research: 3 results,  Invited: 1 results)

  • [Journal Article] In vitro properties of Ag-containing calcium phosphates2016

    • Author(s)
      O. Gokcekaya, K. Ueda, T. Narushima, K. Ogasawara, H. Kanetaka
    • Journal Title

      40th Int'l Conf & Expo on Advanced Ceramics & Composites, Next Generation Bioceramics and Biocomposites

      Volume: - Pages: -

    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Synthesis and characterization of Ag-containing calcium phosphates with various Ca/P ratios2015

    • Author(s)
      O. Gokcekaya, K. Ueda, T. Narushima and C. Ergun
    • Journal Title

      Materials Science and Engineering: C

      Volume: 53 Pages: 111-119

    • DOI

      10.1016/j.msec.2015.04.025

    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Control of Ag release from Ag-containing calcium phosphates in simulated body fluid2015

    • Author(s)
      O. Gokcekaya, K. Ueda and T. Narushima
    • Journal Title

      Ceramic Transactions

      Volume: 254 Pages: 13-20

    • DOI

      10.1002/9781119190134.ch2

    • Peer Reviewed
  • [Journal Article] In vitro evaluation of Ag-containing calcium phosphates2015

    • Author(s)
      O. Gokcekaya, K. Ueda, T. Narushima, K. Ogasawara
    • Journal Title

      Twenty-Fourth International Symposium on Processing and Fabrication of Advanced Materials Proceedings

      Volume: - Pages: 95-103

    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] In vitro properties of Ag-containing calcium phosphates2016

    • Author(s)
      O. Gokcekaya, K. Ueda, T. Narushima, K. Ogasawara, H. Kanetaka
    • Organizer
      40th Int'l Conf & Expo on Advanced Ceramics & Composites
    • Place of Presentation
      Hilton Daytona Beach Resort and Ocean Center, Daytona Beach, Florida, USA
    • Year and Date
      2016-01-24 – 2016-01-29
    • Int'l Joint Research
  • [Presentation] In vitro evaluation of Ag-containing calcium phosphates2015

    • Author(s)
      O. Gokcekaya, K. Ueda, T. Narushima, K. Ogasawara
    • Organizer
      Twenty-Fourth International Symposium on Processing and Fabrication of Advanced Materials
    • Place of Presentation
      Centenary Memorial Hall, Senriyama Campus, Kansai University, Osaka, Japan
    • Year and Date
      2015-12-18 – 2015-12-20
    • Int'l Joint Research / Invited
  • [Presentation] Antibacterial activity and cytotoxicity of Ag-containing calcium phosphates2015

    • Author(s)
      Ozkan Gokcekaya、上田恭介、成島尚之、小笠原康悦、金髙弘恭
    • Organizer
      日本金属学会 第157回大会(2015年秋期)
    • Place of Presentation
      九州大学, 福岡市
    • Year and Date
      2015-09-16 – 2015-09-18
  • [Presentation] Evaluation of antibacterial activity of Ag-containing calcium phosphates2015

    • Author(s)
      K. Ueda, O. Gokcekaya, T. Narushima, K. Ogasawara, H. Kanetaka
    • Organizer
      The 10th Anniversary International Workshop on Biomaterials in Interface Science
    • Place of Presentation
      Baden-ya Soho, Zao
    • Year and Date
      2015-08-04 – 2015-08-05
    • Int'l Joint Research
  • [Presentation] Ag含有リン酸カルシウムの抗菌性評価2015

    • Author(s)
      上田恭介、関山雅人、Ozkan Gokcekaya、成島尚之、小笠原康悦
    • Organizer
      粉体粉末冶金協会平成27年度春季大会
    • Place of Presentation
      早稲田大学国際会議場, 新宿区
    • Year and Date
      2015-05-26 – 2015-05-28

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Published: 2016-12-27  

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