Science des Procédés Céramiques et de Traitements de Surface (SPCTS)

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Centre National de la Recherche Scientifique (CNRS)
Université de Limoges
Ecole Nationale Supérieure de Céramique Industrielle (ENSCI)


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Accueil du site > Axes de recherche > Axe 1 "Procédés céramiques" > Biocéramiques fonctionnalisées > Functionalized bioceramics

Functionalized bioceramics

Contact

Eric CHAMPION : eric.champion unilim.fr


Context/objectives

Our main focus is the functionalization of phosphocalcic bioceramics. We aim developing osteoinductive implantable medical devices by grafting molecules that promote the process of biomineralization, and/or able to provide a therapeutic treatment by incorporation and controlled release of active substances.

Our activity involves the control of chemical formulations, microstructures and architectures of materials for their therapeutic and/or biological functionalization.


Activities

Control of the chemistry of bioceramics

The stoichiometric phophocalcic hydroxyapatite Ca10(PO4)6(OH)2 (denoted as HA) is widely used as synthetic bone substitute for its osteoconduction properties. The apatite structure allows for many substitutions of biological interest on each of its ionic sites.

Two research directions are now being developed :

Silicated apatites

The interest of such silicated apatites lies less in their intrinsic ability to improve the biological properties than in the possibility to use silicated groups as privileged sites for covalent grafting at the surface of the ceramic. These sites are used to functionalize the surface of bioceramics by molecules (adhesion proteins, RGD peptides ...) that are active in the process of bone mineralization.

 
Sintering temperature and silicated HA decomposition as a function of Si content   MG63 osteoblast cell proliferation on titanium, HA et silicated SixHA (*p <0,05)
Biomimetic nanocrystalline apatites

Contrary to the biological apatite, synthetic hydroxyapatite has a low bioreactivity directly related to its highly crystallized nature resulting from a high temperature sintering. This is not the case of biomimetic nanocrystalline apatites which are composed of polysubstituted nanoparticles, non-stoichiometric and weakly crystallized, surrounded by a surface layer containing hydrated non-apatitic phosphate ions of high mobility. Consolidation at very low temperatures by SPS (Spark Plasma Sintering) preserves these characteristics.

 
Density evolution and and material composition after Spark Plasma Sintering as a function of a) the applied pressure and (b) the temperature

Microstructures, architectures and therapeutic functionalization

Phosphocalcic ceramic matrices with controlled porosity are developed in the form of solid blocks or spherical granules. In all cases, the porosity is tailored to enable inclusion and controlled release of active species, thereby improving bioavailability by the localized delivery of therapeutic substances.

Massive implants with controlled porosity

Calibrated polymethylmethacrylate (PMMA) microspheres are used as structuring agent (Fig. a). A HA nanopowder (Fig. b) is dispersed and stabilized in aqueous suspension by the addition of polyethyleneimine. A mixed suspension PMMA-HA is prepared by mixing suspensions of HA and PMMA. The surface charges of the two solid entities being of opposite polarity, the heterocoagulation leads to the formation of core@shell structures (PMMA microspheres coated with HA, Fig. c). The organic / inorganic composite is then calcined in air at 500°C to remove the PMMA microspheres, then sintered to obtain the final ceramic with controlled porosity (Fig. d).

(a) PMMA microspheres, (b) HA nanoparticles, (c) PMMA microspheres coated with HA nanoparticles, (d) sintered porous ceramic
Porous phosphocalcic spheroids

Phosphocalcic spheroids are manufactured by wet granulation at high shear rate. Starch is used as a binding agent and also plays the role of porogen. The total porosity after calcination is of the order of 75%. Those porous spheroids are then loaded in ibuprofen, enabling treatment of post-operative inflammation, by vacuum impregnation from an ethanol solution. The in vitro dissolution curves show the influence of calcination on the kinetics of the drug release. After in vitro dissolution of all of the active substance, the spheroids maintain their integrity.

 
Porous TCP (Tri-calcium Phosphate) spheroids and dissolution kinetics of ibuprofen (phosphate buffer solution, pH = 7.48 and 37°C)


Key facts

  • Integration in 2008 in our group of 4 staff members of the GEFSOD Laboratory (Functionalization of divided solids for pharmaceutical applications), Faculty of Pharmacy, Limoges
  • Since 2008, strong thematic reorientation towards the functionalization of bioceramics (grafting of peptides, pre-bone cell adhesion, inclusion and release of active substances...)
  • In 2010, Dr. Joël Brie, surgeon and Head of the "maxillofacial surgery and restorative dentistry" service of the University Hospital of Limoges, joined our team

Updated May 25, 2012

© SPCTS - Centre Européen de la Céramique - 12 Rue Atlantis - 87068 LIMOGES Cedex - Tél : 05 87 50 23 03 - Fax : 05 87 50 23 09 - Courriel : spcts unilim.fr