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Bioprinted skin model accurately reacts to irritants

In experiments conducted by scientists at the University of São Paulo, the performance of a model obtained in a 3D printer was equivalent to that of the conventional model produced manually. Photo by: FCF-USP

A bioprinted human epidermal skin model performed as well as a manually-produced model at detecting irritants in a new study, published in Bioprinting.

In a press release, the researchers note that bioengineered skin has become an increasingly important and reliable platform for researchers to test the safety and efficacy of drugs and cosmetics. However, there has been little research comparing its performance to that of traditional manually produced models.

In the study, the researchers compared the conventional mimetic model based on manual pipetting with extrusion bioprinting, which “allows the in vitro reconstruction of a more relevant and representative model of human skin”, according to the authors of the article.

“Calling the model ‘artificial skin’ makes it sound synthetic, but actually it’s human tissue that closely resembles natural skin and is very suitable for safety and efficacy testing of bioactive compounds,” said Silvya Stuchi Maria-Engler, PhD, in the release. Dr. Maria-Engler is a professor and researcher at the University of São Paulo’s School of Pharmaceutical Sciences (FCF-USP) Department of Clinical and Toxicological Analysis, in Brazil.

The research team used quality control and performance assessment standards established by international institutions such as the Organization for Economic Cooperation and Development (OECD) as validation criteria for the skin model.

“The first was tissue morphology, which should be representative of human skin in vivo, with a stratified epidermis containing four layers: stratum basale, spinosum, granulosum, and corneum. This means that in vitro reconstructed skin has the same functions as natural skin, which contains a selective barrier against the external medium for protection against chemical stressors [pollutants and topically applied products] and physical stressors [sunlight], while also retaining water,” said Denisse Esther Mallaupoma Camarena, PhD, co-first author of the article and a postdoctoral fellow at FCF-USP.

The next step was to assess the performance of the bioprinted skin as a barrier. To test this function, the researchers exposed the model to sodium dodecyl sulfate (SDS), a detergent that causes skin irritation, at different concentrations for 18 hours.

The last validation test involved topical application of reference irritants and non-irritants. From this last test the investigators found that the histology and cytoarchitecture of both in vitro reconstructed skin models to be consistent with internationally validated epidermic models. The quality of the bioprinted skin was as good as that of the manually reconstructed skin. Both responded equally well to irritants and distinguished between these and non-irritants.

“These findings prove that our bioprinted skin can be used instead of the Draize test, an acute toxicity test that applies the substance directly to rabbit skin. Besides the avoidance of animal testing, it’s less subject to human error and variability in the responses obtained by the cosmetics industry,” said Julia de Toledo Bagatin, first author of the article and a PhD candidate at FCF-USP.

The authors caution that even though their results suggest that bioprinted skin can be used as a platform to test irritation in the laboratory, there is still a need for caution in using bioprinters.

“[Bioprinters] produce mimetic tissue by cell dispersion using a needle or conical nozzle, and depending on the system chosen, there may be cellular response alterations in the in vitro irritation test,” Dr. Maria-Engler said. “Bioprinting is now being used in many fields, so it’s extremely important to acknowledge that the dispersion system chosen can damage the reliability of the tests by leading to altered responses, such as increased inflammation.”

The researchers plan to bioprint more complex models comprising epidermis, dermis, and hypodermis with representative human skin cells, according to the release. They suggest this will help the model more closely mimic real skin and produce more biologically relevant responses in safety and efficacy testing of products for topical use.


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