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Impact of the chemical composition of poly-substituted hydroxyapatite particles on the in vitro pro-inflammatory response of macrophages

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Abstract

To improve the biological properties of calcium phosphate (CaP) bone substitute, new chemical compositions are under development. In vivo such materials are subject to degradation that could lead to particles release and inflammatory reactions detrimental to the bone healing process. This study aimed at investigating the interactions between a murine macrophage cell line (RAW 264.7) and substituted hydroxyapatite particles presenting promising biological properties. Micron size particles of stoichiometric and substituted hydroxyapatites (CO3 substitution for PO4 and OH; SiO4 substitution for PO4; CO3 and SiO4 co-substitution) were obtained by aqueous precipitation followed by spray drying. Cells, incubated with four doses of particles ranging from 15 to 120 μg/mL, revealed no significant LDH release or ROS production, indicating no apparent cytotoxicity and no oxidative stress. TNF-α production was independent of the chemistry of the particles; however the particles elicited a significant dose-dependent pro-inflammatory response. As micron size particles of these hydroxyapatites could be at the origin of inflammation, attention must be paid to the degradation behavior of substituted hydroxyapatite bone substitute in order to limit, in vivo, the generation of particulate debris.

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Acknowledgments

The authors would like to thank Agathe Figarol and Andréa Kurtz-Chalot for their help regarding the biological evaluation of the particles. The authors wish to thank the IFRESIS (Institut Fédératif de Recherche en Sciences et Ingénierie de la Santé) for the financial support provided for this work.

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Authors and Affiliations

  1. Ecole Nationale Supérieure des Mines, CIS-EMSE, CNRS:UMR 5307, 158 cours Fauriel, F 42023, Saint-Etienne, France

    Nathalie Douard & David Marchat

  2. SFR IFRESIS, Saint-Etienne, France

    Nathalie Douard, Lara Leclerc, Gwendoline Sarry, Valérie Bin, David Marchat, Valérie Forest & Jérémie Pourchez

  3. Ecole Nationale Supérieure des Mines, CIS-EMSE, 158 cours Fauriel, F 42023, Saint-Etienne, France

    Lara Leclerc, Gwendoline Sarry, Valérie Forest & Jérémie Pourchez

  4. LINA EA4624, Laboratoire Interdisciplinaire d’Etude des Nanoparticules Aérosolisées, Université Jean Monnet, 10 rue de la Marandière, 42270, Saint-Priest en Jarez, France

    Lara Leclerc, Gwendoline Sarry, Valérie Bin, Valérie Forest & Jérémie Pourchez

  5. Faculté de Médecine Jacques Lisfranc, Université Jean Monnet, 10 rue de la Marandière, 42270, Saint-Priest en Jarez, France

    Valérie Bin

Authors
  1. Nathalie Douard
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  2. Lara Leclerc
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Correspondence to Nathalie Douard.

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Douard, N., Leclerc, L., Sarry, G. et al. Impact of the chemical composition of poly-substituted hydroxyapatite particles on the in vitro pro-inflammatory response of macrophages. Biomed Microdevices 18, 27 (2016). https://doi.org/10.1007/s10544-016-0056-0

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  • DOI: https://doi.org/10.1007/s10544-016-0056-0

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