Projet ANR-07-BLAN-0373 – nanoBiocer : Nouvelle génération de biocéramiques résorbables par consolidation à basse température d'apatites nanocristallines biomimétiques
Programme : Blanc (BLANC) 2007
Année de financement : 2007
Coordinateur du projet : INSTITUT NATIONAL POLYTECHNIQUE DE TOULOUSE (INSTITUT NATIONAL POLYTECHNIQUE DE TOULOUSE)
Partenaires : Institut national polytechnique de Toulouse; Université de Limoges
Montant : 330000.0 euros
Date de début : 2008
Durée : 36 mois
Résumé : Nonstoichiometric nanocrystalline apatites constitute biomimetic nanomaterials analogous to bone mineral. Their high reactivity (strong capability to uptake ions and adsorb organic molecules of biological interest) is due to the presence of a structured hydrated layer on nanocrystals surface. However, the sintering of such phases by conventional techniques (high temperature) leads to strong alterations of their physico-chemical characteristics (dehydration, crystal growth, evolution toward stoichiometry, increased stability, decreased solubility...) and biological properties (poor surface reactivity, low cell adhesion rates). The goal of this project is to prepare innovative highly-bioactive and resorbable bioceramics (porous and non-porous), by low-temperature consolidation of nanocrystalline apatites, while conserving the nanometer dimensions and nonstoichiometry of the initial powders, since these characteristics were shown to control their reactivity and resorption rate in vivo. Several low-temperature consolidation routes will be investigated and optimized in this project: uni-axial pressing at low temperature, apatite gel hardening, and Spark Plasma Sintering (SPS). In particular, SPS is a non-conventional sintering technique where the heating source is provided by pulses of an intense electrical current passing through the sample located in a conducting mold, which enables fast heating and cooling rates. With these three techniques, we will exploit the high ionic mobility from the nanocrystals hydrated layer, which can lead to strong crystal-crystal fusion processes, even at low temperature where regular ionic diffusion processes are not favored. Our preliminary studies showed that it was possible to use such consolidation techniques for obtaining ceramic-like compacts, with interesting mechanical properties. Such ceramics will be prepared and thoroughly characterized, their mechanical properties will be evaluated and the consolidation mechanisms will be investigated. During all the duration of the project, thorough in vitro testing will be developed (subcontracted). In addition to the regular tests performed using bone marrow stem cells, an extended study will be performed here with stem cells isolated from the adipose tissue, which represents a great potential for finding alternative ways than using bone marrow stem cells. The use of mesenchymal stem cells is motivated by the fact that biomaterials used for anchoring hip prostheses or filling bone defects could, in addition to osteoblasts, be in contact with mesenchymal stem cells in bone marrow. Biomaterials could have an effect on their further development, so an experiment on this cell type could also be full of information from this point of view. One objective of this experiment is thus to evaluate the influence of the biomaterial on the different cell types met in the vicinity of bone. At last, in vivo assessments will be achieved for validating the bioceramics.  This multi-disciplinary project gathers 2 partners. A good equilibrium will be searched between a fundamental approach (e.g. understanding consolidation mechanisms at low temperature, use of non-conventional procedures for in vitro testing...) and more applied aspects (in view of a possible future development of this technology). The fundamental approach will represent an important part of the research to be carried out by the PhD student who will be recruited in co-direction between the two partners.                                                                                                                                                                                                                                                                ...