Non invasive imaging for the monitoring of new-vascularization of biomaterials promoting bone repair
As a result of ageing, of various life trauma/accidents and/or bone diseases (osteoporosis for example), the number of bone factures and trauma dramatically increases especially in the most industrialized countries where it raises a public healthcare issue. The number of bone graft procedures performed each year has increased by 10% since 2004, and the global bone graft substitute market value expands by about 20% every 5 years. Clinical alternatives to autografts and allografts include the use of biomaterials such as bioceramics, metallic implants (e.g. titanium alloys) or natural polymers. Nevertheless, in the field of bone tissue regeneration, while reconstruction of small to moderate sized bone defects using engineered bone tissues is technically feasible, the reconstruction of large volume defects remains challenging because of a defect of vascularization. The other challenge in regenerative medicine concerns the non invasive techniques used for imaging bone tissue regeneration. The goal of this project is to developed i) new innovative angiogenic materials for bone tissue reconstruction and ii) non invasive MR bioimaging methods for investigating the perfusion of the implants and predict the success of the bone grafts. To achieve these goals, our project will thus involve the design of novel matrices (polysaccharide+nHA) through innovative chemical modifications (fucoidan and/or strontium doping) promoting angiogenesis. This will be performed with the help of Inserm U698 and Teknimed as a Company specialist in Biomaterials. Regarding experimental developments, this project will consist in developing new MR protocols, including MR acquisitions for anatomical and perfusion imaging and MR data analysis in bone sites. Our project, will allow the development of innovative technology for Ultra short echo time (UTE double echo) sequences and ultra-fast imaging for dynamic contrast enhanced perfusion imaging. This will be performed with UMR CNRS 5536 and CRCTB-PTIB in strong interaction with Bruker as a company, specialist in high field MR equipment development and robust software for data acquisitions and treatment. Regarding the preclinical aspect, we will evaluate in small and large animals the angiogenic properties as well the osteoinductive/osteoconductive properties of the new matrices in ectopic and orthotopic sites by using MRI as a non invasive and non-ionizing imaging technique. This will be performed with the help of Inserm U1026, composed of researchers and clinicians (oral and orthopaedic surgeons). The benefit of this new approach by MRI compared to other methods such as scanner-CT and echo-doppler will be evaluated in this InéoV project. Finally, this project should open a new way for clinicians for proposing a new non-ionizing technique procedure for imaging, in a single exam, the osteointegration of the bone graft and its perfusion.
As a result of ageing, of various life trauma/accidents and/or bone diseases (osteoporosis for example), the number of bone factures and trauma dramatically increases especially in the most industrialized countries where it raises a public healthcare issue. The number of bone graft procedures performed each year has increased by 10% since 2004, and the global bone graft substitute market value expands by about 20% every 5 years. Clinical alternatives to autografts and allografts include the use of biomaterials such as bioceramics, metallic implants (e.g. titanium alloys) or natural polymers. Nevertheless, in the field of bone tissue regeneration, while reconstruction of small to moderate sized bone defects using engineered bone tissues is technically feasible, the reconstruction of large volume defects remains challenging because of a defect of vascularization. The other challenge in regenerative medicine concerns the non invasive techniques used for imaging bone tissue regeneration. The goal of this project is to developed i) new innovative angiogenic materials for bone tissue reconstruction and ii) non invasive MR bioimaging methods for investigating the perfusion of the implants and predict the success of the bone grafts. To achieve these goals, our project will thus involve the design of novel matrices (polysaccharide+nHA) through innovative chemical modifications (fucoidan and/or strontium doping) promoting angiogenesis. This will be performed with the help of Inserm U698 and Teknimed as a Company specialist in Biomaterials. Regarding experimental developments, this project will consist in developing new MR protocols, including MR acquisitions for anatomical and perfusion imaging and MR data analysis in bone sites. Our project, will allow the development of innovative technology for Ultra short echo time (UTE double echo) sequences and ultra-fast imaging for dynamic contrast enhanced perfusion imaging. This will be performed with UMR CNRS 5536 and CRCTB-PTIB in strong interaction with Bruker as a company, specialist in high field MR equipment development and robust software for data acquisitions and treatment. Regarding the preclinical aspect, we will evaluate in small and large animals the angiogenic properties as well the osteoinductive/osteoconductive properties of the new matrices in ectopic and orthotopic sites by using MRI as a non invasive and non-ionizing imaging technique. This will be performed with the help of Inserm U1026, composed of researchers and clinicians (oral and orthopaedic surgeons). The benefit of this new approach by MRI compared to other methods such as scanner-CT and echo-doppler will be evaluated in this InéoV project. Finally, this project should open a new way for clinicians for proposing a new non-ionizing technique procedure for imaging, in a single exam, the osteointegration of the bone graft and its perfusion.

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