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

Nathalie Douard (1, 2, 3) , Lara Leclerc (3, 4, 2) , Gwendoline Sarry (3, 4, 2) , Valérie Bin (4, 2, 5) , David Marchat (1, 2, 3) , Valérie Forest (3, 4, 2) , Jérémie Pourchez (3, 4, 2)

1 LGF-ENSMSE - Laboratoire Georges Friedel
2 IFRESIS - Institut Fédératif de Recherche en Sciences et Ingénierie de la Santé
3 CIS-ENSMSE - Centre Ingénierie et Santé
4 LINA-ENSMSE - Laboratoire Interdisciplinaire d'Etude des Nanoparticules Aérosolisées
5 Faculté de Médecine Jacques Lisfranc [Université Saint-Etienne]

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 (CO 3 substitution for PO 4 and OH; SiO 4 substitution for PO 4; CO 3 and SiO 4 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 2 behavior of substituted hydroxyapatite bone substitute in order to limit, in vivo, the generation of particulate debris.

Mots clés: substituted hydroxyapatite; macrophage; cytotoxicity; inflammation

Domaines: Génie des procédés

Nathalie Douard, Lara Leclerc, Gwendoline Sarry, Valérie Bin, David Marchat, et al.. Impact of the chemical composition of poly-substituted hydroxyapatite particles on the in vitro pro-inflammatory response of macrophages. Biomedical Microdevices, 2016, 18 (2), ⟨10.1007/s10544-016-0056-0⟩. ⟨hal-01321154⟩