Researchers in Spain report that they have developed a 3-D bioprinter capable of producing human skin that is adequate for transplant into patients, or for testing drugs and cosmetics.
The team, including a group from the Universidad Carlos III de Madrid (UC3M) in Spain, describes the breakthrough in the journal Biofabrication.
3-D printing is an emerging new technology with applications in many fields. In medicine, for example, several groups worldwide are exploring ways to use 3-D printing to grow the complex tissues and organs of the human body.
One of the challenges of making human body parts with 3-D printing is not only replicating the complexity of the structures, but also ensuring that they survive transplantation in a living body.
The researchers in Spain have already been engineering plasma-based, two-layered skin that has been used successfully to treat burns and other wounds in a large number of patients.
With this method, however, it can take 3 weeks to produce the amount of skin required to cover an extensive burn or large wound. The other drawback is that much of the process is performed manually.
In the new study, the authors report how the 3-D bioprinting method they developed generated a large (100 x 100 centimeters) area of skin in under 35 minutes – including the 30 minutes “required for fibrin gelation.”
Instead of the cartridges of colored inks normally associated with printing, the 3-D bioprinter uses biological components. Experts say that these “bio-inks” are the key to the successful 3-D printing of human tissue and organs.
As with their existing plasma-based, manual method, the skin-printing technology that the team from Spain has developed generates two layers of skin: the epidermis and the dermis.
It prints the epidermis, including the stratum corneum (the protective outermost layer comprising keratinized cells). Then, it prints the deeper, thicker dermis, complete with fibroblasts that make collagen (the protein that gives skin its strength and elasticity).
One of the researchers, Juan Francisco del Cañizo of the Hospital General Universitario Gregorio Marañón and Universidad Complutense de Madrid, notes:
“Knowing how to mix the biological components, in what conditions to work with them so that the cells don’t deteriorate, and how to correctly deposit the product is critical to the system.”
A computer controls the bioprinting process in order to precisely deposit the bio-inks on a print bed to make the skin.
The researchers carried out two types of test on the skin: one in test tubes and the other – to test for more long-term effects in a living animal – after transplantation into immunodeficient mice. They note the results:
“In both cases, the generated skin was very similar to human skin and, furthermore, it was indistinguishable from bilayered dermo-epidermal equivalents, handmade in our laboratories.”
The team sees two applications for the new technique. One is to produce non-person-specific skin from a stock of cells on a large scale for research and laboratory-testing of cosmetics and drugs. The other is to produce person-specific skin using cells from individual patients to treat burns and other wounds.
The 3-D bioprinter only uses human components to produce active skin that makes its own human collagen. The researchers note that, unlike other methods, it does not use animal collagen.
The bio-inks used in the study are patented by the Center for Energy, Environmental and Technological Research (CIEMAT) in Madrid. They are licensed to the BioDan Group, a private Spanish bioengineering firm that is commercializing the technology. Both CIEMAT and BioDan collaborated on the study.
“This method of bioprinting allows skin to be generated in a standardized, automated way, and the process is less expensive than manual production.”
Alfredo Brisac, CEO of BioDan Group
The 3-D bioprinter has been submitted for approval by various European regulators. The approval is needed to ensure that the printed skin is suitable for transplanting into patients with burns and other skin conditions.
The team is also exploring how to use the new technology to print other human tissues.
The following video (in Spanish with English subtitles) from UC3M demonstrates the new 3-D bioprinter.