by Elton Alisson, FAPESP
Photo of the Human Skin Equivalent with Hypodermis (HSEH) developed by researchers at the Brazilian Biosciences National Laboratory. Credit: LNBio
Brazilian researchers have used three-dimensional (3D) printing to develop an artificial skin model with properties that are more similar to those of human skin. The structure, called Human Skin Equivalent with Hypodermis (HSEH), could be used in studies to treat diseases and injuries such as wounds and burns, as well as in the development of medicines and cosmetics, without the need for animal testing.
The process of producing the material, which is made from stem cells (capable of transforming into different cell types) and primary cells (grown directly from human tissues), was described in the journal Communications Biology by scientists from the Brazilian Biosciences National Laboratory (LNBio), part of the Brazilian Center for Research in Energy and Materials (CNPEM).
The work was presented on November 27 at a session on biotechnology held during FAPESP Week Spain in Madrid. The event, which ended on November 28 at the Faculty of Medicine of the Complutense University of Madrid (UCM), in the Moncloa-Aravaca region, aimed to strengthen links between researchers from the state of São Paulo and the European country in order to promote research partnerships.
“We were able to develop a complete skin model with three layers: the epidermis, dermis and hypodermis. In this way, we were able to obtain a model of the organ with characteristics very similar to those of a human being,” Ana Carolina Migliorini Figueira, researcher at LNBio-CNPEM and coordinator of the project, told Agência FAPESP.
According to Figueira, 3D skin models have been explored as an alternative method to using animals, for example, in cosmetics absorption testing. But the limitation of the options developed so far is that they neglect the hypodermis – the deepest layer of the skin, which plays a fundamental role in regulating important biological processes such as hydration and cell differentiation.
This layer, formed by adipose (fat) cells, plays an active role in the skin, influencing processes such as water regulation, cell development and immunity, making it essential for creating complete and functional skin models.
The researchers used tissue engineering techniques to improve the technology and succeeded in building a full-thickness human skin equivalent with the hypodermis to create an environment closer to real human tissue, allowing for more efficient cell adhesion, proliferation and differentiation.
“This new 3D skin model with the hypodermis layer provides a more accurate in vitro platform for disease modeling and toxicology studies,” concluded Figueira.
“The results of the tests we performed show that the hypodermis is essential for modulating the expression of a wide range of genes that are vital for skin functionality, such as those related to tissue protection and regeneration,” she said.
Diabetic skin
The researchers used 3D bioprinting to build a skin model based on collagen, which serves as a matrix for cell interaction.
LNBio will produce the skin for its own studies, but will also be able to produce the material for partner research institutions. The idea is to help develop grafts for treating wounds and burns.
Through another project, the Brazilian researchers intend to use this more realistic 3D skin to develop a model of diabetic skin with chronic wounds and, consequently, a dressing for this purpose.
The idea is that the LNBio researchers will be able to vascularize the in vitro human skin model in three layers to create a version that mimics the skin characteristics of people with diabetes, who may have wounds that are difficult to heal and are at risk of limb amputation.
In contrast, a group of Dutch researchers affiliated with the Radboud University Medical Center is working to develop new biomaterials to create a dressing to treat diabetic wounds.
“Our goal, once the new dressing is produced, is to test it both in an animal model and on the human diabetic skin that we’ll develop,” Figueira explained.
Biosensors for monitoring
Meanwhile, a group of researchers from the Federal University of ABC (UFABC), also in Brazil, intends to use synthetic biology tools to build biosensors based on genetic circuits, such as DNA, RNA and proteins, to monitor the contamination of environmental samples, such as water, by metals.
By combining biological and engineering knowledge, the researchers aim to introduce new functions in natural organisms by developing new genetic sequences.
“There are natural RNA and protein molecules that can interact with mercury and manganese, for example. The idea is to design these genetic circuits, mainly from bacteria, to monitor the contamination of water samples by these metals, in real time and in a less costly way, without the need to use robust and expensive equipment,” Milca Rachel da Costa Ribeiro Lins, professor at UFABC and coordinator of the project, told Agência FAPESP.
The field of biotechnology is believed to be strategic for Spain and has received large investments from the UCM in recent years, emphasized Spanish researchers who participated in the event.
“The United States remains the world leader in the biotechnology market. But countries in Europe, Asia, Central America and the Middle East are showing very high growth. And Spain has several strong points. One of them is that there are around 4,500 companies working in this field,” said Maria Isabel de la Riesco, a professor at UCM.
Biotechnology companies in Spain employ more researchers than other industries and salaries in the field are higher than the national average, she said.
“Spain has a 2.46% share of the world’s publications of biotechnology-related articles, and their citation rate is 21% higher than the global average. About 60% of the scientific production in biotechnology in the country is carried out in international collaboration,” stated Riesco.
More information: Thayná M. Avelino et al, Unveiling the impact of hypodermis on gene expression for advancing bioprinted full-thickness 3D skin models, Communications Biology (2024). DOI: 10.1038/s42003-024-07106-4
Journal information:Communications Biology
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