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Titanium induces proinflammatory and tissue-destructive responses in primary human macrophages

Implants and medical devices are efficient and practical therapeutic solutions for a multitude of pathologies. Titanium and titanium alloys are used in orthopedics, dentistry, and cardiology. Despite very good mechanical properties and corrosion resistance, titanium implants can fail due to inflamma...

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Main Authors: Gudima, Alexandru (Author) , Hesselbarth, David (Author) , Li, Guanhao (Author) , Riabov, Vladimir (Author) , Michel, Julia (Author) , Liu, Quan (Author) , Schmuttermaier, Christina (Author) , Jiao, Zhen (Author) , Sticht, Carsten (Author) , Jawhar, Ahmed (Author) , Obertacke, Udo (Author) , Klüter, Harald (Author) , Vrana, Nihal Engin (Author) , Kzhyshkowska, Julia (Author)
Format: Article (Journal)
Language:English
Published: October 2024
In: Journal of leukocyte biology
Year: 2024, Volume: 116, Issue: 4, Pages: 706-725
ISSN:1938-3673
DOI:10.1093/jleuko/qiae072
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.1093/jleuko/qiae072
Verlag, kostenfrei, Volltext: https://academic.oup.com/jleukbio/article/116/4/706/7633045
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Author Notes:Alexandru Gudima, David Hesselbarth, Guanhao Li, Vladimir Riabov, Julia Michel, Quan Liu, Christina Schmuttermaier, Zhen Jiao, Carsten Sticht, Ahmed Jawhar, Udo Obertacke, Harald Klüter, Nihal Engin Vrana, and Julia Kzhyshkowska
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Summary:Implants and medical devices are efficient and practical therapeutic solutions for a multitude of pathologies. Titanium and titanium alloys are used in orthopedics, dentistry, and cardiology. Despite very good mechanical properties and corrosion resistance, titanium implants can fail due to inflammatory or tissue degradation-related complications. Macrophages are major immune cells that control acceptance of failure of the implant. In this study, for the first time, we have performed a systematic analysis of the response of differentially activated human macrophages, M(Control), M(IFNγ), and M(IL-4), to the polished and porous titanium surfaces in order to identify the detrimental effect of titanium leading to the tissue destruction and chronic inflammation. Transcriptome analysis revealed that the highest number of differences between titanium and control settings are found in M(IL-4) that model healing type of macrophages. Real-time quantitative polymerase chain reaction analysis confirmed that both polished and porous titanium affected expression of cytokines, chitinases/chitinase-like proteins, and matrix metalloproteinases (MMPs). Titanium-induced release and activation of MMP7 by macrophages was enhanced by fibroblasts in both juxtacrine and paracrine cell interaction models. Production of titanium-induced MMPs and cytokines associated with chronic inflammation was independent of the presence of Staphylococcus aureus. MMP7, one of the most pronounced tissue-destroying factors, and chitinase-like protein YKL-40 were expressed in CD68+ macrophages in peri-implant tissues of patients with orthopedic implants. In summary, we demonstrated that titanium induces proinflammatory and tissue-destructing responses mainly in healing macrophages, and the detrimental effects of titanium surfaces on implant-adjacent macrophages are independent on the bacterial contamination.
Item Description:Online veröffentlicht: 21. März 2024
Gesehen am 18.12.2024
Physical Description:Online Resource
ISSN:1938-3673
DOI:10.1093/jleuko/qiae072

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