Community Research and Development Information Service - CORDIS

H2020

VIVOIMAG Report Summary

Project ID: 645757
Funded under: H2020-EU.1.3.3.

Periodic Reporting for period 1 - VIVOIMAG (Multimodal imaging of the in vivo fate of bone transplants)

Reporting period: 2015-06-01 to 2017-05-31

Summary of the context and overall objectives of the project

Millions of bone grafts are being performed worldwide to repair large segments of bone lost due to trauma, surgery and other causes. It is estimated that the bone graft market exceeds $2.5 billion/year. A continuously ageing population forecasts a steady increase in those numbers. Autologous bone transplants (those in which the recipient and donor are the same patient) have large osteogenic potential and present no biocompatibility problems, but they have several problems and risks that can be avoided using engineered tissue. Bone harvests, mostly taken from the iliac crest, rib, fibula, or tibia of the patients’ bone, do not always provide sufficient quantities, and can be associated with potential complications of pain, blood loss, infection, and radiation injury. On the other hand, engineered tissue does not have these drawbacks. In addition, it is also cost effective, since it can be produced and delivered to the patient at a point of care environment. However, there are important challenges to address since the technology strongly relies on the correct cell differentiation within the scaffold, therapeutic solutions that use adult bone marrow derived cells lack the complexity and structure associated with the bone tissue required for repair and lack of vascularisation in the engineered tissue result in necrosis after implantation. Thus the need for novel and efficient methods to produce efficient bone grafts, as well as assess the success of bone treatments has high social importance.
The main objective of VIVOIMAG H2020-MSCA-RISE-2014 project 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. the main objectives of the project are to: i) Develop new magnetically labelled contrast agents capable of detecting metaloproteases enzymatic activity; ii) Incorporate these new materials within scaffolds used for bone regeneration; iii) Develop bone tissue bioreactors and implant regenerated tissue into animal models; iv) Grow 3D high-density bone graft based on multi-cells cultures; v) Exploit state of the art MRI and nuclear medicine imaging to evaluate and optimize the capacity of the contrast agent within the implants for detecting in vitro and in vivo enzymatic activity of metaloproteases and vi) Detection local metaloprotease activity in real time to follow cell differentiation in the bone engineered bioreactor in vitro and in vivo.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

"WP2: Development of contrast agents
Initially several radiolabelling strategies of magnetic nanoparticles (MNPs), including the design of ligands were employed to enable stable conjugation of the radioisotopes on MNPs. Characterization and in vitro stability and in vivo imaging results are reported.

WP3: Incorporation of contrast agents into bioreactors and grafts
Initially experience among participants was shared mostly on the exchange of cells and the performance of cell cultures, so that cell models are available in different laboratories, to asses various labelling strategies in vitro. Cells and technology were provided by BONUS. BIOIMAG provided collagen. CSIC experience on performed assays and DEMO hosted cell cultures.

WP4: In vivo imaging of cell differentiation, inflammation and integration of grafts
Initial in vivo images of MNPs either labelled with Tc99m, or using MRI were obtained by BET and UMONS. In the second Year of the project in vivo tasks were focused on implementing bone defects on mice and testing the procedures required to visualize and quantify the defects, as well as monitoring the evolution of therapy. The advantages and disadvantages of techniques available inside the consortium were examined.

WP5: Dissemination / Exploitation / Training
Conferences
1. Multimodal imaging as a tool to non-invasively assess in bone regeneration: The VIVOIMAG project, George Loudos, 27th Interdisciplinary Research Conference on Injectable Osteoarticular Biomaterials and Bone Augmentation Procedures, Athens, Greece, on 18-20 May 2017.
2. ""Collagen scaffolds labelled with MRI and SPECT contrast agents for non-invasive imaging in bone tissue engineering"", European Molecular Imaging Meeting, Cologne, 4-7 April 2017.
3. ""Impact of 99mTc-labelling on binding and viability of human adipose tissue-derived cells in vitro and on the cell-tracking properties using SPECT in vivo"", Balcan Congress of Nuclear Medicine, Thessaloniki 17-20 June 2016.

Workshops
1. ""Multimodal imaging of the in vivo fate of bone transplants: VIVOIMAG"", 3rd NANO-GR Workshop - 14th International Conference on Nanosciences & Nanotechnologies (NN17), 4-7 July 2017, Thessaloniki, Greece
2. ""Radiolabelling Of Magnetic Collagen Scaffolds For Bone Tissue Engineering"", Annual meeting of TD1402 RADIOMAG COST Action, Athens 7-8 April 2016.
3. ""Multimodal imaging of the in vivo fate of bone transplants: VIVOIMAG"", Annual meeting of TD1004 Theranostic COST Action, Belgrade 10-11 September 2015."

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

1.3.1 Enhancement of innovation capacity
The project is positioned in the field of biomedical engineering and preclinical and clinical research. The domain of bone regeneration has very good potential to have social impact, since it addresses issues related to aging and thus can potentially affect all citizens. The approach of using nanotechnology to non-invasively, early asses the treatment of bone defects is novel and can be clinically translated if the use of collagen, decorated with MNPs is proven to detect enzymatic activity. At the moment, several variations and combinations of nanoparticles and collagen are tested, in order to define, which have the potential to provide MR contrast, since the proper selection initial biomaterials is critical for successful proof of project hypothesis. In addition, the techniques available in the consortium are explored and further optimized, since it is the first time that multimodal approaches are used in bone regeneration combined with nanomedicine. Thus, the results of this work will be reference data from future research. Finally, the development of proper animal models and imaging protocols is also unique and careful steps are needed, to establish and test procedures, which can be further exploited in tissue engineering research.
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