title: Impact of the chemical composition of poly-substituted hydroxyapatite particles on the in vitro pro-inflammatory response of macrophages.
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.
authors.affiliation: Ecole Nationale Supérieure des Mines, CIS-EMSE, CNRS:UMR 5307, 158 cours Fauriel, F 42023, Saint-Etienne, France. douard@emse.fr.|SFR IFRESIS, Saint-Etienne, France. douard@emse.fr.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Douard
authors.affiliation: SFR IFRESIS, Saint-Etienne, France.|Ecole Nationale Supérieure des Mines, CIS-EMSE, 158 cours Fauriel, F 42023, Saint-Etienne, France.|LINA EA4624, Laboratoire Interdisciplinaire d'Etude des Nanoparticules Aérosolisées, Université Jean Monnet, 10 rue de la Marandière, 42270, Saint-Priest en Jarez, France.
authors.forename: Lara
authors.initials: L
authors.lastname: Leclerc
authors.affiliation: SFR IFRESIS, Saint-Etienne, France.|Ecole Nationale Supérieure des Mines, CIS-EMSE, 158 cours Fauriel, F 42023, Saint-Etienne, France.|LINA EA4624, Laboratoire Interdisciplinaire d'Etude des Nanoparticules Aérosolisées, Université Jean Monnet, 10 rue de la Marandière, 42270, Saint-Priest en Jarez, France.
authors.forename: Gwendoline
authors.initials: G
authors.lastname: Sarry
authors.affiliation: SFR IFRESIS, Saint-Etienne, France.|LINA EA4624, Laboratoire Interdisciplinaire d'Etude des Nanoparticules Aérosolisées, Université Jean Monnet, 10 rue de la Marandière, 42270, Saint-Priest en Jarez, France.|Faculté de Médecine Jacques Lisfranc, Université Jean Monnet, 10 rue de la Marandière, 42270, Saint-Priest en Jarez, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Bin
authors.affiliation: Ecole Nationale Supérieure des Mines, CIS-EMSE, CNRS:UMR 5307, 158 cours Fauriel, F 42023, Saint-Etienne, France.|SFR IFRESIS, Saint-Etienne, France.
authors.forename: David
authors.initials: D
authors.lastname: Marchat
authors.affiliation: SFR IFRESIS, Saint-Etienne, France.|Ecole Nationale Supérieure des Mines, CIS-EMSE, 158 cours Fauriel, F 42023, Saint-Etienne, France.|LINA EA4624, Laboratoire Interdisciplinaire d'Etude des Nanoparticules Aérosolisées, Université Jean Monnet, 10 rue de la Marandière, 42270, Saint-Priest en Jarez, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Forest
authors.affiliation: SFR IFRESIS, Saint-Etienne, France.|Ecole Nationale Supérieure des Mines, CIS-EMSE, 158 cours Fauriel, F 42023, Saint-Etienne, France.|LINA EA4624, Laboratoire Interdisciplinaire d'Etude des Nanoparticules Aérosolisées, Université Jean Monnet, 10 rue de la Marandière, 42270, Saint-Priest en Jarez, France.
authors.forename: Jérémie
authors.initials: J
authors.lastname: Pourchez
mesh_terms: D000818:Animals; D018786:Bone Substitutes / Q000737:chemistry* / Q000494:pharmacology*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D055598:Chemical Phenomena; D017886:Durapatite / Q000737:chemistry* / Q000494:pharmacology*; D007249:Inflammation / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects; D010316:Particle Size; D000067996:RAW 264.7 Cells; D017382:Reactive Oxygen Species / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D018786:Bone Substitutes; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D017886:Durapatite
keywords: Cytotoxicity; Inflammation; Macrophage; Substituted hydroxyapatite