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MaTissE Report Summary

Project ID: 648779
Funded under: H2020-EU.1.1.

Periodic Reporting for period 1 - MaTissE (Magnetic approaches for Tissue Mechanics and Engineering)

Reporting period: 2015-07-01 to 2016-12-31

Summary of the context and overall objectives of the project

While magnetic nanomaterials are increasingly used as clinical agents for imaging and therapy, their use as a tool for tissue engineering opens up challenging perspectives that have rarely been explored. Lying at the interface between biophysics and nanomedicine, and based on magnetic techniques, MaTissE aims to magnetically design functional tissues and to explore the tissular fate of nanomaterials.
Designing purely cellular 3D tissue substitute is a major challenge for regenerative medicine to avoid the use of synthetic scaffold. Also, the biophysics community still need to answer pressing questions on the role of physical stresses in cell and tissue functions, such as differentiation. In parallel, when using scaffolds, one current challenge is to provide means for controlling the cellular 3D organisation. Finally, another important concern in nanomedicine, and one that is rarely addressed, is the fate of the nanoparticles in the biological environment. Meaning what do the nanoparticles become after achieving their therapeutic intracellular mission. There is currently a lack and a need for reliable methodologies to measure in real time the fate and persistence of nanoparticles in bio-tissular systems.
MaTissE aims at providing magnetic solutions to these issues, by (i) creating 3D tissues without a supporting matrix, (ii) applying controlled stimulation to such tissular constructs, and (iii) exploring in situ using nanomagnetic methods the nanoparticles fate.

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

Since the beginning of the project, the first prototype of a magnetic tissue bioreactor has been produced and successfully tested with embryonic stem cells, with the demonstration of a remote magnetic control of stem cells differentiation. We are currently moving to a second prototype for the muscle tissue engineering and in situ force measurements involved. In parallel, tissue rheology with magnetic forces was initiated. We have also designed a magnetic field applicator to allow magnetic cardiomyocytes alignment, and we are currently testing the functionality of the 3D constructs so-created. Finally, we have tested different protocols to allow a better cartilage differentiation, and we have implemented magnetic cartilage tissue engineering in scaffolds, as the first start towards a multi-layer magnetic cartilage engineering.
Concerning the nanofate of nanoparticles, we have implemented new methods to track the long-term intracellular and tissular fate of nanoparticles, and we have demonstrated a massive intracellular biodegradation, which could be prevented by a gold shell on the iron oxide nanoparticles. We are currently exploring the role of stem cells differentiation on the biodegradation, and of nanoparticles coating. We are also exporting the innovative methodologies introduced to other metallic nanoparticles, embedded in a tissue construct.

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)

"The development of the magnetic tissue stimulator, involving a set of innovative magnetic approaches based on initial cell magnetization, followed by the use of a magnetic micro-attractor array for 3D cell assembly and a micro-controlled attractor network to manipulate the model tissue without direct contact, is original. It is unique in that it provides an ""all-in-one"" solution: the same device is used to create the model tissue and to stimulate it throughout its maturation, for example in a cyclical manner that mimics cardiac muscle contraction. This innovative approach has already allowed us to gain insights into embryonic stem cells differentiation. We hope to manage to use it for the production of unprecedented tissue replacement structures.
In parallel, we have provided a first multimethod, multiscale quantitative study of intracellular iron oxide nanoparticle degradation, showing an unexpected near-total nanoparticle degradation during long-term maturation of a stem cell model tissue. Both the methods developed to track quantitatively the intracellular fate of nanoparticles and the exploration of nanodegradation as a function of nanoscale features (for instance shielding iron oxide by a gold shell) are fundamental for all uses of nanoparticles in medical devices and applications."
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