Early in vitro response of macrophages and T lymphocytes to nanocrystalline hydroxyapatites

• Macrophage/lymphocyte response to nanocrystalline hydroxyapatites was evaluated.
• Nanocrystalline hydroxyapatites decreased macrophage proliferation and phagocytosis.
• Increased production of inflammatory cytokines IL-6 and TNF-α was detected.
• T lymphocyte apoptosis was increased without proliferation changes.
• Nanocrystalline hydroxyapatites might induce early immune system activation.

HypothesisSynthetic hydroxyapatite (HA) and Si substituted hydroxyapatite (SiHA) are calcium phosphate ceramics currently used in the field of dentistry and orthopaedic surgery. The preparation of both biomaterials as polycrystalline solid pieces or grains formed by nanocrystallites has awakened a great interest to enhance the bioactive behavior due to the microstructural defects and the higher surface area. The study of the macrophage and lymphocyte behavior in contact with nanocrystalline HA and SiHA will allow to elucidate the immune response which conditions the success or rejection of these biomaterials.ExperimentsHA and SiHA granules (with sizes of tens of microns) have been prepared by controlled aqueous precipitation avoiding subsequent high temperature sintering. HA and SiHA granules were constituted by crystallites smaller than 50 nm. The effects of both nanocrystalline materials on immune system have been evaluated with macrophages (main components of innate immune system) and T lymphocytes (specific cells of adaptive response) after short-term culture as in vitro models of the early immune response.FindingsSignificant decreases of macrophage proliferation and phagocytic activity, increased production of inflammatory cytokines (IL-6, TNF-α) and T lymphocyte apoptosis, were induced by these nanocrystalline ceramics suggesting that, after in vivo implantation, they induce significant effects on immune responses, including an early activation of the innate immune system.

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