Researchers from Universidad Carlos III de Madrid (UC3M), Universidad Politécnica de Madrid (UPM) and other entities have designed a new biochip, a device that simplifies the process of in vitro manufacturing of skin in the laboratory and other complex multi-layered fabrics. Human skin modeled using this device could be used in medical and cosmetic testing, reducing the cost of such preclinical testing.
This biochip is made of biocompatible and micro-machined adhesive vinyl sheets. “Most microfluidic devices are developed using ultraviolet lithography, a very expensive and complex technique that requires highly specialized instruments and highly trained personnel. In contrast, our technology is very inexpensive, accessible to all laboratories and versatile, because its design can be modified virtually for free,” explains one of the researchers, Leticia Valencia, from the Tissue Engineering and Regenerative Medicine-Integrative Biomedicine (TERMeG-INTEGRA) research group in the Department of Bioengineering and Aerospace Engineering at the ‘UC3M.
The biochip allows the culture of skin in vitro inside the biochip. It is divided into two superimposed channels, separated by a porous membrane: blood flow is simulated in the lower channel; the skin is generated in the upper channel, which is nourished by the culture medium flowing into the lower channel via the membrane.
All flows are controlled by very precise syringe pumps and the procedure is performed in a cell culture room and sterile environment. The biochips are incubated in a controlled humidity atmosphere with 5% CO2 and a temperature of 37°C.”
Ignacio Risueño, Scientist, Department of Bioengineering and Aerospace Engineering, UC3M
This platform and the techniques developed were tested in a proof of concept which consisted in the generation of a three-dimensional skin with its two main layers. The dermis was modeled using a fibrin hydrogel, while the epidermis was created using a keratinocyte monolayer that is seeded onto the fibrin gel. In addition, the researchers developed a new method for controlling the height of the dermis based on parallel flow, a technique that allows an in situ deposition process of the dermal and epidermal compartments.
This research work does not have a clinical objective but rather aims to replace animal models in medical and cosmetic tests, as these tests can be performed directly on this microfluidic platform. Indeed, European directives prohibit the manufacture of cosmetic products tested on animals and encourage the application of the 3Rs (Replacement, Reduction and Refinement) in animal research.
“While it cannot be directly applied to a patient in a clinical setting, it would allow studies to be carried out on personalized skin models. This would involve taking cells via a biopsy from a patient and creating the model of skin into the microfluidic device using their skin cells. This could be used as a patient-specific check to examine a particular patient’s response to a treatment or medication,” the researchers explain.
The biochip and the protocols developed could be extrapolated to any other complex tissue having the same structure as the skin. Additionally, it could be used to more easily model tissues consisting of a single monolayer of cells, such as in most “organs on a chip”. This cell culture system simulates the main functional aspects of living organs but on a microscopic scale, which can be used to develop new drugs and a less expensive alternative to animal testing in toxicology studies and clinical trials.
The future challenges are to secure mature skin, that is to say skin with a completely differentiated epidermis, with all its layers. In addition, the integration of biosensors making it possible to monitor the condition of the skin in real time could be studied, as well as the experimentation of this model as a test method.
This line of research, which has led to various publications in scientific reports and other scientific journals, includes researchers from UC3M, UPM, the Center for Energy, Environmental and Technological Research (CIEMAT, in its acronym Spanish), from the Clínico San Carlos Hospital, the Health Research Institute of the Gregorio Marañón Hospital and was carried out within the BIOPIELTEC-CM project of the Community of Madrid.
Carlos III University of Madrid
Valence, L. et al. (2021) A new microfluidic method enabling the generation of multi-layered tissue on chips using skin cells as proof of concept. Scientific reports. doi.org/10.1038/s41598-021-91875-z.