Periodic Reporting for period 2 - VIVOIMAG (Multimodal imaging of the in vivo fate of bone transplants)
Berichtszeitraum: 2017-06-01 bis 2019-05-31
The main objective of VIVOIMAG is to develop bone implants including a new contrast agent sensitive to enzymatic activity of metaloproteases, which will permit for the first time to follow the integration and cell differentiation activity in bone tissue bioreactors in vitro and in grafts in vivo using non invasive imaging techniques. The final goal of the project is to provide this collagen based contrast agent and use standard MRI as a tool to assess the efficiency of new bone treatments. In this way a clinically available, non invasive and affordable technology will be exploited for tissue engineering.
After the completion of the action, these goals were indeed met. Bone implants were designed and constructed providing the ability to promote enzymatic activity of metaloproteases and the capability to be labeled with different contrast agents. Thus, they can be monitored through multi-modal imaging techniques. In addition, a complete multi-modal imaging platform, that enables the complementary efficiency evaluation of new bone graphs, has been established.
WP2 focused on developing magnetically modified contrast agents for MRI imaging that are sensitive to enzymatic activity and radiolabel them to work also as contrast agents for nuclear imaging. Different methodologies were used to attach MNPs on the collagen and to test through several characterization techniques the resulting structural, stability, magnetic and sensitivity to enzymes activity related properties. As a result, contrast agents that are magnetically modified for MRI imaging and that are sensitive to enzymatic activity were created, also in a form that is easily radiolabelled to also act as nuclear scintigraphic contrast agents.
WP3 focused on incorporating contrast agents into 3D high-density bone grafts and hydrohyapatite microparticles to read non-invasively metaloprotease activity in multicell bioreactors in vitro and in vivo.
The method to incorporating the MNPs to the mineralized scaffold was established and samples were characterized using infrared spectroscopy, thermal gravimetry, X ray diffraction, SEM, AFM and magnetic studies. Once the hybrid Coll/HA material was prepared, it was extensively washed and lyophilized and sterilized through gamma rays to prepare the scaffold materials ready to use in the in vivo experiments.
As a result, incorporating the MNPs to the mineralized scaffold was successfully performed, creating homogeneously labelled materials that have been confirmed to properly allow bone regeneration.
WP4 focused on following the evolution of cell differentiation, inflammation and integration of grafts in animal models using non-invasive imaging.
The main task of this WP, included the creation of an animal defect model and the dispersion of the prepared collagen material on the small animal bone injury models (mice) to be monitored through SPECT and CT imaging. The procedure to also incorporate the magnetic nanoparticles (MNPs) as a contrast agent was followed and MRI tests were performed to validate the image contrast induction.
Results proved the creation and establishment of a complete imaging platform that can non-invasively monitor the evaluation of new bone graphs, in bone formation schemes, through multi-modal imaging. The complementary information gathered through SPECT, CT and MRI imaging was demonstrated and exploited towards the creation of the imaging platform.
WP5 focused on ensuring efficient communication and dissemination of project outcomes to dedicated and broader audience, incorporating several training activities. By the closing of the project the several activities were completed including:
Creation of project logo, poster, brochure and website. Citation in social media.
Participation in public events, workshops, conferences, satellite events.
2 publications in peer-review journals.
Training activities (1 summer school, 2 courses, 1 PhD thesis, 1 scholarship).