Our bodies are complex machines where millions of chemical reactions take place at the same time. Melanin pigments that give human skin, hair and eyes their color, are produced by multiple step reactions. There are different types of melanins (brown/dark and yellow/red) and skin color depends on the proportion and distribution of each. Melanins are activated thanks to a process called melanogenesis, when three enzymes react.
Three enzymes are responsible for the activation of melanins. They are called tyrosinases (TYR, TYRP1 and TYRP2) and their exact function is unknown. The reason for this is that until now scientists have never managed to purify the human version in large quantities to study them. Instead, they have been using the fungal or plant enzymes to synthesize inhibitor compounds.
In the picture: Crystal structure of TYRP1. Tyrosine (the substrate metabolised) is bound to the active site, which contains the zinc metal ions (red spheres).
Scientists also unveiled an unexpected result: they found that TYRP1 needs zinc to function, contrary to the established belief in the community that this enzyme needs copper. “We still don’t know exactly what role zinc takes in the interaction with TYRP1 and we need extensive further research to find that out”, explains Montse Soler López, main researcher of the study.
There are several ways of testing drugs and cosmetics for future use in humans. Since 2013 animal testing for cosmetics is totally forbidden in the EU so the options are either cell culture, which does not recreate the physiological conditions, or reconstructed skin.
His work with Montse Soler López and Catherine Belle's teams consists of testing the compounds developed by Belle's group on pigmented bioprinted skin and it is part of the Cosmethics cross-disciplinary project of the UGA. This is the closest they'll be to a human skin.
So how do you print human skin? Human skin is incredibly complex. The epidermis is made of 90% keratinocytes, 1-3% of immunity cells and 7-9% of melanocytes. One melanocyte distributes melanins to 36 keranocytes. Rachidi and his colleagues try to increase the complexity of the skin's bio-printed models by including other cell types, such as vessel cells, in order to be as close as possible to normal human skin.
Rachidi's team collaborates with industrial partners in developing creams that are safe to whiten the skin and remove marks. With a huge market in Asia and Africa, current whitening creams are toxic not only for the skin, but also for the internal organs. The only inhibitors that are clinically available (hydroquinone, retinoids and arbutin) are toxic and not safe.