PARIS – Microlight3D SAS, based in La Troche, France, is about to receive a $900,000 grant from the EU to develop new 3D printer technology dedicated to treating acute wounds and chronic ulcers that do not heal. "It's about developing a novel process based on ion-releasing biomaterials promoting angiogenesis for skin regeneration," Denis Barbier, optoelectronics laser specialist and CEO of Microlight3D, told BioWorld.

According to the study, based on data collected between 1990 and 2015 in more than 195 countries and published in The Lancet, the global burden of skin and subcutaneous diseases has increased rapidly over 10 years, with an incidence of 605 million in 2015 compared to 493 million in 2005. That is an increase of 23% in 10 years. As many as 20 million people globally were reported as living with acute wounds in 2009 as a result of surgery or chronic skin ulcers. Wound care is associated with significant costs and has become a major challenge to health care systems worldwide. In France, the national reimbursement system spends $10 billion each year on treating wounds that do not heal. In the U.K., the National Health Service (NHS) spends between $5.6 billion and $6.4 billion managing these wounds. Faced with these statistics, strategies are being sought to improve healing rates. Microlight's concept was to "incorporate its new patented 3D printer technology into creating cell support structures used in a tissue engineering process intended to accelerate regeneration and facilitate healing," said Barbier.

Microlight3D is one of five European partners working together on the nAngioderm project, starting this September and running for three years. The lead partner, the Spanish-based Institute for Bioengineering in Catalonia (IBEC), is responsible for bringing its research skills in bioactive ions and bioengineering to the nAngioderm project. The laboratory of Biophysics, Biochemistry, Bioprocessing and Bioproducts (University of Ioannina, Greece), the Department of Plastic Sciences and Burns at the University Hospital Vall d'Hebron in Barcelona (Spain) and the interdisciplinary laboratory of physics (Liphy) at the Grenoble Alpes University are also involved in this European R&D project. Approximately $1.5 million will be invested in all in nAngioderm, half coming from the EU and the other half from French, Greek and Spanish partners.

nAngioderm will develop nanostructured ion-release platforms and devices that promote in-situ regeneration of damaged cells. The innovative approach is based on the release of bioactive ions (Zn2 +, Ag +, Ca2 +) from biodegradable polymeric nanocarriers, which will be developed using a nano-precipitation technique. These bioactive ions will promote cell recruitment and colonization and provide an antibacterial effect, as well as trigger the synthesis of angiogenic factors and extracellular matrix components that will facilitate wound healing. "Depending on the type of skin injury, the ion-releasing nanocarriers will be combined with 3D printed collagen-based scaffolds as filling and guiding biomaterials for chronic wounds such as diabetic or pressure ulcers, or dispersed in a spray, based on a thermo-responsive collagen gel for acute wounds related to burns," said Barbier.

A compact 3D printer featuring submicron resolution

"Collaborating with such high-level academic organizations on such a key health issue is further recognition of the value of our 3D microprinting technology in regenerative medicine applications," said Barbier. Founded in 2016, Microlight3D is a spin-off from Liphy, based at Genoble-Alpes University. It is the result of 15 years of research at this laboratory on laser-matter interaction and the phenomenon of two photon non-linear optical polymers. Developed by Patrick Baldeck and Michel Bourdiau (co-founder and technical director of Microlight3D), the device is based on two-photon polymerization technology for direct laser writing as well as on its proprietary continuous printing technology. "Manufacturers can use this method to free themselves from the constraints of the conventional "layer-by-layer" additive approach, that limits the 3D printing resolution to 25µ," said Barbier. The company already markets its high-resolution 3D micro-printers for industrial and scientific applications.

The Altraspin 3D printer, designed for printing active wound dressings includes a femtosecond pulse laser source (a half-nanosecond pulse), optics to focus the laser beam, and finally micromechanical elements to move the laser beam very precisely around the collagen cells to print a micro dermal cytoskeleton (dermal cell scaffold). Software with two proprietary algorithms and adapted sample holder makes it easy to control this new generation of 3D tissue printer.

A printing system that works directly in the collagen structure

Unlike thermal micro-printers and those using conventional photo-polymerization, the Microlight3D printer works directly in the collagen structure. This technology is no longer limited to printing layer-by-layer. "Micro-skeleton printing achieves a writing resolution of around 0.2µ, which is 100 times finer than the best 3D printers on the market," said Barbier. An advantage over the only competitor in two-photon polymerization micro-printing: the German Nansocribre GmbH.

Microlight3D, which counts the Grenoble Alpes University among its shareholders, invests more than half a million dollars each year in R&D, and files a new patent every year. It has won several prizes and awards: the I-Lab Grand Prize from the French Ministry of Research last year, and the startup prize awarded seven months ago by the LABO Forum in Paris, the benchmark technical and scientific event in France for suppliers of laboratory materials and services. "The devices and platforms proposed here will be assessed in vitro and in suitable preclinical in vivo models as per EMA guidelines, bringing them to technology readiness level 4-5, close to clinical translation and market transferability stages," said Barbier.

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