title: Early in vitro response of macrophages and T lymphocytes to nanocrystalline hydroxyapatites.
abstract: OBJECTIVE
  Synthetic 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.
  
  
  METHODS
  HA 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.
  
  
  RESULTS
  Significant 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.
authors.affiliation: Department of Biochemistry and Molecular Biology I, Faculty of Chemistry, Universidad Complutense, 28040 Madrid, Spain. Electronic address: conchitamatesanz@hotmail.com.
authors.forename: María Concepción
authors.initials: MC
authors.lastname: Matesanz
authors.affiliation: Department of Biochemistry and Molecular Biology I, Faculty of Chemistry, Universidad Complutense, 28040 Madrid, Spain. Electronic address: mjfeito@pdi.ucm.es.
authors.forename: María José
authors.initials: MJ
authors.lastname: Feito
authors.affiliation: Department of Biochemistry and Molecular Biology I, Faculty of Chemistry, Universidad Complutense, 28040 Madrid, Spain. Electronic address: monaderr@bio.ucm.es.
authors.forename: Mercedes
authors.initials: M
authors.lastname: Oñaderra
authors.affiliation: Department of Biochemistry and Molecular Biology I, Faculty of Chemistry, Universidad Complutense, 28040 Madrid, Spain. Electronic address: cecilia27884@hotmail.com.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Ramírez-Santillán
authors.affiliation: Department of Biochemistry and Molecular Biology I, Faculty of Chemistry, Universidad Complutense, 28040 Madrid, Spain. Electronic address: cdacasa_19991@hotmail.com.
authors.forename: Carmen
authors.initials: C
authors.lastname: da Casa
authors.affiliation: Department of Inorganic and Bioinorganic Chemistry, Faculty of Pharmacy, UCM, Instituto de Investigación Sanitaria Hospital 12 de Octubre i+12, 28040 Madrid, Spain; Networking Research Center on Bioengineering, Biomaterials and Nanomedicine, CIBER-BBN, Spain. Electronic address: arcosd@farm.ucm.es.
authors.forename: Daniel
authors.initials: D
authors.lastname: Arcos
authors.affiliation: Department of Inorganic and Bioinorganic Chemistry, Faculty of Pharmacy, UCM, Instituto de Investigación Sanitaria Hospital 12 de Octubre i+12, 28040 Madrid, Spain; Networking Research Center on Bioengineering, Biomaterials and Nanomedicine, CIBER-BBN, Spain. Electronic address: vallet@farm.ucm.es.
authors.forename: María
authors.initials: M
authors.lastname: Vallet-Regí
authors.affiliation: Department of Cellular and Molecular Medicine, Centro de Investigaciones Biológicas, CSIC, 28040 Madrid, Spain. Electronic address: jmrojo@cib.csic.es.
authors.forename: José María
authors.initials: JM
authors.lastname: Rojo
authors.affiliation: Department of Biochemistry and Molecular Biology I, Faculty of Chemistry, Universidad Complutense, 28040 Madrid, Spain. Electronic address: portoles@quim.ucm.es.
authors.forename: María Teresa
authors.initials: MT
authors.lastname: Portolés
mesh_terms: D056704:Adaptive Immunity; D000327:Adsorption; D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry / Q000494:pharmacology*; D002417:Cattle; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D006882:Hydroxyapatites / Q000737:chemistry / Q000494:pharmacology*; D007113:Immunity, Innate; D015850:Interleukin-6 / Q000096:biosynthesis / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D010587:Phagocytosis / Q000187:drug effects / Q000276:immunology; D012710:Serum Albumin, Bovine / Q000737:chemistry; D012825:Silicon / Q000737:chemistry; D013499:Surface Properties; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000378:metabolism
chemical_list: D001672:Biocompatible Materials; D006882:Hydroxyapatites; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D012710:Serum Albumin, Bovine; D012825:Silicon
keywords: Biocompatibility; Cytokine; Hydroxyapatite; Lymphocyte; Macrophage