title: *Biomimetic Versus Sintered Calcium Phosphates: The In Vitro Behavior of Osteoblasts and Mesenchymal Stem Cells.
abstract: The fabrication of calcium phosphates using biomimetic routes, namely, precipitation processes at body temperature, results in distinct features compared to conventional sintered calcium phosphate ceramics, such as a high specific surface area (SSA) and micro- or nanometric crystal size. The aim of this article is to analyze the effects of these parameters on cell response, focusing on two bone cell types: rat mesenchymal stem cells (rMSCs) and human osteoblastic cells (SaOS-2). Biomimetic calcium-deficient hydroxyapatite (CDHA) was obtained by a low temperature setting reaction, and α-tricalcium phosphate (α-TCP) and β-tricalcium phosphate were subsequently obtained by sintering CDHA either at 1400°C or 1100°C. Sintered stoichiometric hydroxyapatite (HA) was also prepared using ceramic routes. The materials were characterized in terms of SSA, skeletal density, porosity, and pore size distribution. SaOS-2 cells and rMSCs were seeded either directly on the surfaces of the materials or on glass coverslips subsequently placed on top of the materials to expose the cells to the CaP-induced ionic changes in the culture medium, while avoiding any topography-related effects. CDHA produced higher ionic fluctuations in both cell culture media than sintered ceramics, with a strong decrease of calcium and a release of phosphate. Indirect contact cell cultures revealed that both cell types were sensitive to these ionic modifications, resulting in a decrease in proliferation rate, more marked for CDHA, this effect being more pronounced for rMSCs. In direct contact cultures, good cell adhesion was found on all materials, but, while cells were able to proliferate on the sintered calcium phosphates, cell number was significantly reduced with time on biomimetic CDHA, which was associated to a higher percentage of apoptotic cells. Direct contact of the cells with biomimetic CDHA resulted also in a higher alkaline phosphatase activity for both cell types compared to sintered CaPs, indicating a promotion of the osteoblastic phenotype.
authors.affiliation: 1 Biomaterials, Biomechanics and Tissue Engineering Group, Department of Materials Science and Metallurgical Engineering, Technical University of Catalonia , Barcelona, Spain .|2 Centre for Research in Nanoengineering, Technical University of Catalonia , Barcelona, Spain .
authors.forename: Joanna-Maria
authors.initials: JM
authors.lastname: Sadowska
authors.affiliation: 1 Biomaterials, Biomechanics and Tissue Engineering Group, Department of Materials Science and Metallurgical Engineering, Technical University of Catalonia , Barcelona, Spain .|2 Centre for Research in Nanoengineering, Technical University of Catalonia , Barcelona, Spain .
authors.forename: Jordi
authors.initials: J
authors.lastname: Guillem-Marti
authors.affiliation: 1 Biomaterials, Biomechanics and Tissue Engineering Group, Department of Materials Science and Metallurgical Engineering, Technical University of Catalonia , Barcelona, Spain .|2 Centre for Research in Nanoengineering, Technical University of Catalonia , Barcelona, Spain .
authors.forename: Edgar Benjamin
authors.initials: EB
authors.lastname: Montufar
authors.affiliation: 1 Biomaterials, Biomechanics and Tissue Engineering Group, Department of Materials Science and Metallurgical Engineering, Technical University of Catalonia , Barcelona, Spain .|2 Centre for Research in Nanoengineering, Technical University of Catalonia , Barcelona, Spain .
authors.forename: Montserrat
authors.initials: M
authors.lastname: Espanol
authors.affiliation: 1 Biomaterials, Biomechanics and Tissue Engineering Group, Department of Materials Science and Metallurgical Engineering, Technical University of Catalonia , Barcelona, Spain .|2 Centre for Research in Nanoengineering, Technical University of Catalonia , Barcelona, Spain .|3 Institute for Bioengineering of Catalonia , Barcelona, Spain .
authors.forename: Maria-Pau
authors.initials: MP
authors.lastname: Ginebra
mesh_terms: D000818:Animals; D040761:Biomimetic Materials / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D018786:Bone Substitutes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D002516:Ceramics / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D017886:Durapatite / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D008422:Materials Testing; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism*; D051381:Rats
chemical_list: D018786:Bone Substitutes; D017886:Durapatite
keywords: biomimetic hydroxyapatite; calcium phosphate; mesenchymal stem cell; osteoblast