CongOs

Head and neck cancers rank 5th in France and 70% of them are treated with radiotherapy. However some complications can occur, including osteoradionecrosis (ORN) with 5-10% of incidence. This necrosis of the mandibular induces pain, infections, fractures and most of patients can no longer eat orally. While conservative treatments exist for default 1cm2 and its technological transfer to a SME company. The considered materials are aliphatic polyester/bioactive glass composites scaffolds elaborated by the freeze-casting process. Their elaboration involves well-defined and customized nanoscopic building entities and is based on a new strategy that has never been described for biomedical applications and especially for particles/polymers cited above. This new approach allows obtaining bioactive materials with very high and homogeneous mineral filler rate and modular porosity (volume, pore size, anisotropy similar to mandibular bone) and composition. Then these scaffolds could fulfil the multiple requirements of ORN: i) stimulate the formation of new bone in these critical bone defects thanks to cell differentiation and proliferation. ii) be osteoconductive and exhibit high porosity to support cell colonization and angiogenesis. iv) maintain adequate mechanical properties during handling by surgeons, v) have antibacterial and angiogenic properties. The latter aspect is predominant for ORN. Indeed, even a highly bioactive material will be inefficient to treat ORN after implantation, without addressing the bacterial issue. We propose here a twofold approach in order to avoid it with synergistic and/or dual kinetic/mechanistic effect of several kind of active agents. Most importantly, this project aims at assessing the composite scaffold technology including the transfer of whole elaboration process (building blocks and scaffolds) and the development of a freeze-casting apparatus prototype for/by the SME company (no commercial apparatus is currently available). To ensure to reach these main R&D objectives, fundamental chemical, physical and biological studies need to be carried out to establish a link between the elaboration process, the scaffolds properties and their biological behaviour. 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 multidisciplinary project. The consortium includes CIRIMAT in Toulouse, IBMM in Montpellier (both members of Institut Carnot Chimie Balard Cirimat), IUCT in Toulouse, RMeS in Nantes, IMMM in Le Mans and Rescoll in Pessac The work program includes a first step dedicated to the elaboration of nanoprecursors and scaffolds by screening formulation (compositions of bioactive glasses, polymer chain length, nature of the solvent, concentration…) and process (temperature gradient) parameters. It will be followed by the characterization of structural, morphological and mechanical scaffolds properties and the technology transfer to Rescoll. The second step is dedicated to biological properties correlated with the application: i) in vitro studies such as biocompatibility, differentiation / proliferation of cells and antibacterial and angiogenic properties and ii) in vitro behaviour of implanted scaffolds with a new animal model well-adapted to mimic ORN issues. Finally the thirs step is focused on the transfert and the industrial assesment of the technology.