NANOFOROSTEO

The failure of osteosynthesis in case of large bone defect and osteoporosis fracture repair is still a big unmet clinical need in orthopaedics. While autograft is still the gold standard in many clinical circumstances, the use of synthetic bone void fillers does not present issues of amount and shape of bone tissue availability and avoids donation site morbidity. The project NANOFOROSTEO consists of the development of a new injectable void filler based on hyaluronan, chemically modified to include thermo-responsive brushes of poly(N-isopropylacrylamide), Hyal-pN. Such a conjugate maintains the biological features of Hyaluronic Acid, but is able to become stiffer upon temperature increase above 32°C. Then, this new formulated Hyal-pN is potentially able to be easily adapted to the shape of the void to fill, avoiding at the same time the particle's migration once localized at the intended anatomical location. A further novelty of this application resides in loading such thermo-responsive hydrogel with nano-microencapsulated complexes-drug delivery system. Poly (lactic acid), polyglycolic acid, poly-caprolactone and their co-polymers such as poly(lactic-co-glycolic acid) have been extensively used to deliver different molecules (e.g. antibiotics, proteins) through their hydrolytic and enzymatic degradation in vivo and have a long history in the field of drug delivery. Furthermore, multi-substituted nanoHAp will be synthesized and incorporated together with Strontium ranelate in polymer/drug formulations extending the range of nanoHAp/drug complex compositions. The possibility of combining the above hyaluronal thermo-responsive hydrogel features with the nanoHAp technological platform on osteoconductive and on inhibitor of bone resorption particles has a great potentials and it is of value to explore these new line of products/approaches against osteoporosis fracture repair. Furthermore, High Pressure Processes will be used as an innovative method for sterilisation. It is well known the limitations of the present sterilisation approaches (inactivation and degradation). It is therefore, of highest commercial and clinical importance, to evaluate such new sterilization approaches, which could lead to a better functional drugs activity.

· PARTNERS INVOLVED IN THE NANOFOROSTEO PROJECT CONSORTIUM:

Project Coordinator: Prof. Dr. Mauro Alini - AO Foundation, AO Research Institute, Head of Musculoskeletal Regeneration, Davos, Switzerland (WP3, WP4) - Project Partner 1

Project Partner 2: Prof. Dr. Janis Locs - Riga Technical University, Rudolfs Cimdins Riga Biomaterials Innovations and Development Center, Latvia (WP2)

Project Partner 3: Prof. Dr. Alain Largeteau - Centre National de la Recherche Scientifique, Institut de Chimie de la Matière Condensée de Bordeaux, France (WP5)

Project Partner 4: Prof. Dr. Gérard Demazeau - SME, HPBioTECH, France (WP6)

Project Partner 5: Prof. Dr. Maria Tomoaia-Cotisel - Babes-Bolyai University of Cluj-Napoca, Chemical Engineering, Romania (WP1)