THE artificial skin produced by bioengineering has become an increasingly relevant and reliable platform to evaluate the safety and efficacy of medicines and cosmetics, since, in addition to replacing the use of animals, it can be obtained on a large scale.
Among the most promising technologies for model production in vitro, in a laboratory environment, is 3D bioprinting. However, as it was very recent, there was a lack of tests to compare its performance with that of the traditional, manually produced model.
This was the main objective of a study conducted by researchers from the Faculty of Pharmaceutical Sciences at the University of São Paulo (USP). The results, released in the journal Bioprinting, confirm the similarity of performance.
The researchers compared the mimetic model created using the traditional method by pipetting (done with a pipette) with the one produced in bioprinters using the extrusion mechanism, which is the most used and allows for a more representative reconstruction of human skin.
“The fact that we call the model ‘artificial skin’ may give the idea that it is something synthetic, when in fact it is human tissue, extremely similar to natural skin. That is why it lends itself so well to testing the safety and efficacy of bioactive compounds”, explains Silvya Stuchi Maria-Engler, full professor at the Department of Clinical and Toxicological Analysis at the Faculty of Pharmaceutical Sciences at USP.
Quality control and performance standards established by international institutions, such as the Organization for Economic Cooperation and Development (OECD), were used as validation criteria.
“The first was tissue morphology, which should be representative of human skin in vivothat is, it must contain, in the epidermis, the entire structure stratified into four layers: basal, spinous, granulosa and cornea”, explains Denisse Esther Mallaupoma Camarena, first author of the article and postdoctoral fellow at USP.
“This indicates that the skin reconstructed in vitro will present the same functions as ours, which has a selective barrier against the external environment, protecting against chemical stressors [poluição, produtos tópicos aplicados] and physical [radiação solar]also exercising its function of water retention”.
The next step was to evaluate how the bioprinted skin performed as a barrier. Like human skin, artificial skin must be able to withstand the permeation of irritating detergents. For this, they exposed the models to the irritating detergent sodium dodecyl sulfate (SDS) at different concentrations for 18 hours.
The last validation test was then to topically apply reference chemical substances classified as irritating (acids, for example) or non-irritant (physiological solutions).
The results showed that both laboratory-reconstructed skin models exhibited histology and cytoarchitecture consistent with the validated epidermal models, with the bioprint showing as good quality as the manual. Furthermore, they also withstood the permeation of irritating detergents and were able to distinguish these substances from non-irritating ones.
“This conclusion makes it possible to replace the Draize tests used in the past, which used shaved rabbit skin for such classification”, says Julia de Toledo Bagatin, first author of the study and doctoral student at USP. “It also provides less human error and less variability in the response obtained in the cosmetic industry”.
“The dissemination of part of the methods developed favors the use of alternative tests in the cosmetics sector, which do not involve animals, which further expands our commitment to the cause”, points out Juliana Lago, scientific manager at Natura, which supported the study . The company idealized the use of the bioprinter to manufacture skin and financed part of its development.
“The academy brings basic science knowledge, which is invested to acquire scientific knowledge, and our partnership fosters the possibility of accelerating the application of this knowledge in more applied research for the company, in this case knowledge in tissue reconstruction and adaptation to tools of automation, such as bioprinting”.
The study was supported by the State of São Paulo Research Foundation (FAPESP).
Most Reliable Printers
Although the main results of the study show that bioprinted skins can be used as a platform for in vitro irritation testing, the researchers point out that caution must be exercised when using bioprinters.
“The machines produce the mimetic tissues by cellular dispersion, using needles or conical tips, and, depending on the system chosen, there may be alterations in the cellular response to the in vitro irritation test”, explains professor Maria-Engler.
“As bioprinting technology is being widely used in many areas, it is of utmost importance to recognize that the dispersion system chosen can undermine the reliability of these tests by generating altered responses, such as increased inflammation.”
The expectation now is that bioprinting will be used to make more complex models, including the three layers (epidermis, dermis and hypodermis) and representative cells of human skin. This would bring the model even closer to reality and bring more relevant biological responses in safety and efficacy tests of topical use products.
Source: CNN Brasil
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