DS0412 -

Development of new pyrophosphate-based glasses synthesized by soft chemistry for bone regeneration applications – PyVerres

Submission summary

Because of ageing, various life trauma and bone diseases, bone grafts and bone substitutes are being used to replace missing or no longer viable bone tissue. The number of bone grafting procedures will in the next decade reach 500 000 in 2020 in Europe and the sales volumes of high performance synthetic bone substitute grafts with the attractive price tag could reach 4 million cm3 by 2020. Among the synthetic bone substitutes, silicate-based bioactive glasses have clinically proved to be as efficient as autograft in the long term but lack short term performances which are not yet optimal for spinal surgery, fracture consolidation and alveolar ridge augmentation in dental implantology, for which the bone tissue regeneration is needed within four months.

The PyVerres project intends to develop (from fundamental to applied aspects), new pyrophosphate-based glasses (PP-glasses) to regenerate bone tissues in orthopedics and dental applications. These biomaterials, recently patented by CIRIMAT, are composed of pyro- and orthophosphate entities and calcium ions. Their elaboration by soft chemistry (40°C maximum, including the drying steps) and their structure have never been described in the literature before. The nature of these materials and their synthesis process are in line with the need to reduce the manufacturing costs, i.e. cheaper raw materials, low temperature and solvent-free elaboration processes. From the biological point of view, their novelty is mainly associated to the pyrophosphate entities which can be hydrolyzed into orthophosphate ones thanks to chemical and enzymatic (phosphatase enzymes naturally produced by osteoblasts) activities. Their expected tunable properties by biochemical control of the resorption rate (chemical and enzymatic hydrolysis triggered by the pyro/ortho-phosphate ratio) open the way to the design of materials able to induce a specific biological response, and act as biologically active inorganic glasses enhancing the bone healing process.
Most importantly, this project aims at assessing the PP-glasses technology and transferring the low-temperature solvent-free synthesis process and characterization of these novel tunable bioactive glasses to a SME company, Noraker which has successful experiences in technology assessment and has already brought to the market several innovative bioactive glass based products from academic collaborations. To ensure to reach these main R&D objectives, fundamental chemical, physico-chemical and biological studies need to be carried out to establish a link between the elaboration process, the glass compositions and their biological properties.

Therefore a consortium has been formed with 5 academic and 1 industrial partners, providing complementary domains of knowledge and expertise for the good development of this inter- and multidisciplinary PRCE project. The consortium includes two Carnot Institutes, CIRIMAT in Toulouse and Chimie-Balard in Montpellier, the LCMCP in Paris, BioTis U1026 in Bordeaux, B2OA in Paris and Noraker company in Villeurbanne.

The work program includes a 1st step dedicated to the elaboration of glasses by screening synthesis conditions such as composition, pH, temperature, followed by the technology transfer of the low temperature synthesis process to Noraker and, fine structural, morphological and thermal characterizations and modelling. The in vitro study of these glasses reactivity in biological fluids is the 2nd important step, necessary to anticipate the physico-chemical phenomena occurring at the surface or within of the glass in presence or absence of enzymes. Then, biological tests will be conducted: i) in vitro to study the biological response of cells and also of phosphatase enzymes depending on the composition of the glass (pyro/ortho-phosphate ratio) and, ii) in vivo through the animal implantation of new glasses to study their biocompatibility, osteoconductivity and resorbability kinetics compared to commercial bioglass.

Project coordinator

Madame Christèle COMBES (Institut Carnot CIRIMAT - CIRIMAT UMR 5085)

The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.

Partner

LCMCP Laboratoire de Chimie de la Matière Condensée de Paris - UMR 7574
ICGM Institut Carnot Chimie Balard - ICGM UMR 5253
B2OA Bioingénierie et Bioimagerie Ostéo-articulaire - UMR 7052
NORAKER
CIRIMAT Institut Carnot CIRIMAT - CIRIMAT UMR 5085
INSERM INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE

Help of the ANR 687,817 euros
Beginning and duration of the scientific project: January 2017 - 48 Months

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