Scientists bet on 3D printers to create human-like skin

A 3D printer releases an aqueous solution and, in about an hour, it turns into a small material that at first glance looks like plastic. This substance, however, is an artificially manufactured fabric that will be used for cosmetic testing. Today, it replaces the use of animals; in the future, it could be applied to human skin that cannot regenerate.

These are the premises that guide 3BDS, a startup that has a partnership with São Leopoldo Mandic College. The company works with a technology called bioprinting.

“We use living materials, such as human cells, to reconstruct human tissues”, summarizes Ana Luiza Millás, director of research and development at the company and a PhD in chemistry from Unicamp (State University of Campinas).

“Nowadays, it is possible to make small tissues, such as cartilage, bone fragments, skin and tumor models, with bioprint technology, but the promise is that in the future we will have more complex organs to enter the transplant queues. I believe that this will happen in ten to 20 years”, explains the researcher.

The bioprinter automates the construction of biological tissues in a standardized and scalable way. It works through digital files, which are like drawings that the printer reads and prints, layer by layer, in exactly the shape the researcher wants.

When compared to conventional 3D printers, a bioprinter has its differences. It needs to be in a completely aseptic environment, to avoid contamination, and works at a maximum temperature of 37°C. A common 3D printer, for example, can reach up to 240°C, says Millás.

Furthermore, to generate an organic material, the bioprinter uses polymers that are compatible with the human body and biodegradable, such as collagen and hyaluronic acid.

From there, these substances are mixed in an aqueous solution, becoming a hydrogel, and then human cells are added. This entire process results in the so-called biotint, the basic raw material for a bioprinter, which enables the formation of biological tissues.

Currently, 3BDS only works with bioprinting of materials used in the cosmetics industry. These materials simulate real skin, avoiding the use of animals as guinea pigs to test these products, but they do not have the same complexity as the largest organ in the human body.

“We are just making a layer of the skin that works as a barrier against the entry of microorganisms”, explains Millás.

However, the company’s intention is to reach regenerative medicine, a branch of health that works directly with the body of human beings. An example would be the development of a biodressing that could help regenerate skin that has suffered a major burn.

Achieving this goal requires vascularizing the material. A printed tissue that is not vascularized, when applied to a human being, cannot remain healthy for a long time because it would not receive nutrients and oxygen due to the lack of blood vessels.

Developing a vascularized tissue consists mainly of adding more cells, making the printing process more complicated, as it brings it closer to the natural aspect of the human body.

Currently, the startup uses two cell types — keratinocytes and fibroblasts, found in human skin. To vascularize the tissue, it would be necessary to add two more types of cells — the endothelial and the pericytes, related to the formation of blood vessels.

Another challenge in forming vascularized tissues is the technological advance itself. “As you make the number of cells and the size of the structures more complex [dos tecidos], you are putting more and more pressure on technologies [necessárias para a bioimpressão]”says Pedro Massaguer, president of 3BDS.

Ernesto Goulart, a researcher at the Center for the Study of the Human Genome and Stem Cells at USP, works with tissue bioengineering and explains that tissue vascularization can also occur through a process in the human body called angiogenesis, which consists of the formation of spontaneous vessels.

“Cells begin to feel that oxygen is lacking in a tissue and then signal to nearby vascular cells to perform angiogenesis [de forma a formar novos vasos sanguíneos onde está defeituoso]. So it is not necessarily necessary to design the entire vascular system [do tecido impresso] because the body itself can collaborate with angiogenesis”, he says.

The objective of getting as close as possible to natural organs through bioprinting is related to biomimetics, a concept that basically consists of “getting as close as possible to the native tissue [de uma pessoa]”says Millás.

In this case, in addition to vascularizing the tissues to perform the natural functions of human skin, the researchers are also concerned with the visual aspect. According to Millás, the idea is that the material, after being applied, adapts to the body in such a way as to be similar to the rest of the skin.

“Once applied to a wound, the tendency is that [o material] it helps to regenerate tissue and, over time, it will be absorbed by the body. It’s not like a bandage that you put on and then have to take off. In reality, the body itself assimilates”, he explains.

Expectations of validating the use of bioprinted tissues in humans, however, still have a long way to go. The company plans to start preclinical testing on animals of materials without vascularity in January or February 2022 — for those with vascularity, the forecast is for the first half of next year.

It will still be necessary to carry out clinical tests with humans. Only after that, it will be possible to file an evaluation request with Anvisa (National Health Surveillance Agency) to start the authorization of the product.

Goulart also points out that laboratory tests are not enough to indicate the success of a project like this.

“Many times we see a great result in the laboratories and then we test it on animals that may or may not work. If it works, it may be that when it gets to the human it goes wrong. This is because the answers are very different and we are increasing the complexity of the system”, he says.