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I am Christophe Marquette, Director of Research at CNRS (French National Centre for Scientific Research). I have a background in biochemistry and joined the CNRS in 2001. I am conducting research on tools and in-vitro diagnostic devices, for which I set up a company named Axo Science.
I then started to work with 3D, by printing polymers for medical devices and in-vitro diagnostics. We then started to print implantable medical devices and materials. We ended up making a technological platform at the University of Lyon, with 3 laboratories. One for ceramics, one for photochemistry in Lyon ENS, and one oriented towards biology – applied biochemistry.
It arose at first from my need to manufacture diagnostic 3D devices with, at the time, few tools apart from PLA.
We used to have a lot of work to carry on in Photochemistry before we could invest in better-performing machinery. Then with the knowledge we had of biology and materials, we shifted towards research in 3D Printing rather than 3D Printing to conduct research.
Now we are working on processes and materials for 3D Printing, we are patenting material modification techniques to make them printable. In the beginning, it used to be a need for tools, but it shifted to a research thematic to develop these tools.
One of the first things we have patented and is still presently in use is a skin bioprinting technique applied to regenerative medicine (both a process and a formulation). Then we filed three patents on silicone printing, half formulation, and half process. Last year we patented a new printing technique that gave ground to the creation of a new startup for September 2020, that will be dedicated to taking charge of injection materials by 3D Printing. We also patented implantable silicone, intended for implants, and implantable prostheses, without formulation.
3D Bioprinting means printing living cells with control of the 3D structure, and with a functionality at the end of the process. Thus, it doesn’t only consist of cells in a gel, but a function such as a tissue or an organ. It is, by the way, more about tissues than organs.
Regarding the applications, there are two: The first one, regeneration, is the treatment of tissues or failing organs. The second one is in-vitro studies. We will for instance replicate tumours in-vitro with the right shape and composition, to test medications. Other pharmaceutical applications do exist, such as replicating tumours twenty times to try different tests.
Our focus is more about bioprinting of tissues that can be reimplanted. We are working on a project along with the French Army about skin reimplantation for serious burn victims for instance. The goal is to be able to recreate tissues using the patient’s cells. This in turn means no rejection will be encountered, and also that anti-rejection drugs can be avoided.
It is an innovative technological platform. Labels awarded by regions are quite rare, and this one is the only one in additive manufacturing. It gives access to finances for machinery investments, as the specificity is to have a very industrial focus. 50% of the budget comes from the region, while the other 50% comes from contracts with industrial companies. The end goal is to push forward additive manufacturing for medical devices and tissues.
We currently have 15 people working together on these themes, since 2005. As we are carrying out research in 3D and Health, we are a cross-competence team composed of biologists, polymerists, engineers, ceramists and so on. Our projects always deal with different skills.
The first one is the possibility to create customized devices for patients, whether for bioprinting (so that cells get specific to the patient), but also to create specific forms.
Regarding silicon, we work a lot on trachea implants. Tracheas are different from one person to another, and interventions they may encounter also differ. There is an advantage for hospitals and clinics to produce medical devices locally. In the paediatric field for instance, short term trachea implants and silicon oesophagus exist for children with certain pathologies. It is possible to place trachea implants for a few weeks, that are bought at high prices when they could be 3D printed directly at the hospital instead. This would allow implants to be adapted to the patient’s age, as paediatric patients receive implants meant for adults and that are hard to install.
There is also an advantage for manufacturing medical devices which can’t be made with molding. There are for instance cases of trachea parts we achieved with other companies, in which the designs they wanted couldn’t be done with molding. The inner architecture, the topological and optimization were inherent to 3D Printing, but wasn’t feasible with molding.
But this technology also comprises hindrances, the biggest of them being that implantable materials aren’t printable, hence the need to work on this.
We just launched a company called Healshape, who’s mission is to manufacture tissue grafts for patients suffering from breast cancer. The processes are based on our work as well as other companies’ work, and consists in generating tissues meant to be grafted in place of removed breasts, after surgery.This is our biggest project for the next 10 years to come around the 3d.FAB platform.
This is an ambitious project because no other company tackles this issue, as the time to market averages 10 to 12 years and as for all other regenerative medicine projects, returns on investments are long to achieve. For our project concerning serious burn victims, the same issue arises. Sales opportunities are inconsequential, but the social benefits would be important for patients. That’s the kind of projects we are interested in.
In medicine, what would be ideal would be that hospitals provide themselves with ready to use machines for trachea implants, silicon or less invasive part manufacturing. What would be ideal too would be a shift to direct management with short circuits, to create these things internally.
On the regenerative medicine part, it’s a bit different, as specific structures are required. One that already exists in Lyon makes skin to be implanted and I think this is going to skyrocket. The printing component represents only 5 to 10% of bioprinting issues, while the rest is more of a biological order. The obstacle lies on the biological level, on tissue maturation for instance and is expected to evolve in the upcoming years.
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