Biomedical research progress made it possible to tackle diseases and make great medical advances in recent decades. Unfortunately, to the largest extent, experimental research required animal models to move forward. The European Union, through the European Association for Animal Research, strongly regulates animal research following the 3R principle. These are 1) Replacement: to avoid or replace the use of animals; 2) Reduction: minimise the number of animals used per experiment; and 3) Refinement: minimise animal suffering and improve welfare.
In line with European procedures, the BRIGHTER project (Bioprinting by light-sheet lithography: engineering of complex tissues with high resolution at high speed), coordinated by the Institute of Bioengineering of Catalonia (IBEC), was created precisely with the idea of contributing to reduce animal experimentation through the development of new solutions in 3D bioprinting. In this field, also known as tissue engineering or regenerative medicine, 3D printing techniques are increasingly used for biomedical purposes to produce bone, dental and cartilage prothesis. At BRIGHTER, researchers are fabricating human skin, a highly complex tissue, using light for 3D Bioprinting.
New BRIGHTER technology of 3D bioprinting
BRIGHTER is a European Union funded project coordinated by a group of experts from the Biomimetic systems laboratory for cell engineering from IBEC, led by Dr. Elena Martínez. Its main objective is developing and applying Light Sheet Bioprinting for the creation of complex and accurate in vitro models adequate for its use both in the pharmaceutical industry (testing of cosmetics and drugs) and in basic research, reducing animal experimentation.
To reach this end, researchers are developing a new 3D bioprinting technology based on patterned laser light sheet with which they intend to overcome some technical obstacles that currently limit the fabrication of complex human tissues.
"Our innovative 3D bioprinting system not only achieves tissues that are closer to the real ones, but it is also much faster than current systems, a fundamental factor to ensure the viability of the new tissues". Professor Elena Martínez, coordinator of the European project BRIGHTER.
Hydrogels, materials that form the base where the cells will grow and form the new tissue, are a key component in this technology. Hydrogels have properties resembling those found in the cellular environment in vivo (known as the extracellular matrix). This matrix surrounds the cells within the body, providing them with nutrients, tissue-like elasticity and stability. Another very relevant factor is that the entire process can be done in a personalized way, since patient cells can be used to construct the new tissue.
Laboratory printed skin
To fine-tune the new technology, BRIGHTER researchers are printing human skin, a tissue with a highly complex three-dimensional structure made up of multiple cell types and structures such as sweat glands and hair follicles.
On the one hand, the skin made with this new technology can be used as a substitute for animals both in the pharmaceutical and cosmetic industry, as well as in basic research laboratories, being a much more reliable system since it is made from human cells. On the other hand, it can help to respond to the demand for skin in medical interventions, for example, in burns or people suffering from different dermatological diseases.
The advantage of this new technology is that it allows to mould in detail the tissue being printed, which in the case of skin, is crucial since it is a dynamic tissue made up of several layers with different cell types and extracellular matrix composition. In addition, this technology makes it possible to generate vascularization of the tissue and include essential appendages such as the sebaceous (fat) and sweat glands, and the hair follicles that generate hair.
In order to "print" the skin, and for it to adopt its structure, shape and consistency, the researchers use advanced imaging techniques, which combine illumination with light sheets and high-resolution digital photomasks, that allow to pattern the cells inside the hydrogels. They do this by applying laser light directly onto a mixture of materials (hydrogels and cells), which also contains molecules that react to light. In this way, it is possible to mould the new tissue and create its 3D structure on demand, controlling the stiffness, shape and dimensions, thus generating three-dimensional tissues with complex geometry.
"We hope to be able to print a skin sample with an area of 1 cm2 and a thickness of 1 mm in approximately 10 min and with a cell viability of more than 95%, greatly improving current bioprinting conditions". Dr. Núria Torras, postdoctoral researcher at IBEC.
Researchers from three top European research institutions (IBEC in Spain, Goethe Universität Frankfurt in Germany and the Technion center in Israel) participate in the BRIGHTER project, together with leading companies in the biotechnology sector (Mycronic in Sweden and Cellendes in Germany).
BRIGHTER project is funded by FET-open program from the European Commission under the grant agreement nº 828931.