A team of scientists has made major progress in the field of wound repair, developing bioprinted skin that is closer to natural skin than ever before.
Scientists have discovered a way to use 3D printing technology to engineer human skin grafts in the laboratory that have been shown to heal wounds faster than traditional grafts.
Russian scientists create biodegradable 3D scaffolds for bone regeneration
Skin grafting is performed when a person has severe burns or ulcers, and after surgery to remove the cancer. It usually requires surgeons to remove skin from an undamaged part of the body and tape it over the wounds.
In experiments on mice and pigs, researchers found that their skin was able to speed up wound healing with less scarring than usual. This technology could one day help people fully recover from serious burns.
The skin is much more complex than what we see on the surface, as it has three broad layers, each with its own distinct anatomy. When we suffer severe enough wounds or skin diseases, our natural ability to heal is often not enough to fully restore its appearance and function. Temporary and permanent skin grafting (which moves healthy skin from somewhere on the body to the site of injury) has allowed people to survive previously fatal wounds, but the procedure usually does not exactly match the natural appearance of the skin.
Ideally, it would be possible to treat these injuries by encouraging complete regeneration of the damaged skin. Scientists at the Wake Forest Institute for Regenerative Medicine believe they may be able to achieve this goal by turning to bioprinting technology, which uses 3D printing techniques to create more natural, tissue-like structures.
In new research published Wednesday in the journal Science Translational Medicine, the team details how to develop the unique bioprinted skin.
Bioprinting uses a combination of living cells, nutrients and other biological materials to replicate tissue. In this case, Wake Forest Institute scientists developed in vitro skin that mimics the biological composition of human skin using six types of human skin cells: dermal keratinocytes, melanocytes, dermal fibroblasts, dermal follicular papillary cells, and dermal microvascular endothelial cells. And adipocytes.
The cells were placed in vials of a specific type of ink used to print biological materials such as organ tissue.
This ink (specialized hydrogels that act as bio-ink) was then used with all six major types of skin cells, to create a three-by-three-centimeter patch of skin made up of the three layers that make up healthy human skin: the epidermis, dermis, The fatty layer (also called the subcutaneous layer).
The resulting mixture appears to resemble full-thickness human skin, complete with three layers of skin, an obvious precedent that has been impossible until now, according to the scientists.
One shortcoming of previous efforts to develop bioprinted skin is that they contain only two types of cells, the team said.
The scientists then tested the skin on infected mice and pigs. Through these animal experiments, bioprinted skin successfully stimulated the rapid growth of new blood vessels and healthier-looking tissue than typically seen with grafts, ultimately leading to improved wound healing and reduced scarring.
“Comprehensive skin healing is a major clinical challenge, affecting millions of individuals worldwide, with limited options,” Anthony Atala, co-lead author and director of the Wake Forest Institute for Regenerative Medicine, said in a statement from the university. “These results show that creating full-thickness human skin “Bioengineered is possible, promoting faster healing and more natural-looking results.”
Scientists have identified a sixth basic taste that the tongue detects
Scientists have found that the tongue responds to ammonium chloride as the sixth basic taste, in addition to detecting sweet, sour, salty, bitter and umami (popularly known as savory) flavours.
Research published Thursday in the journal Nature Communications suggests that protein receptors on the tongue that help detect sour taste also respond to ammonium chloride, a common ingredient in some Scandinavian candy.
“If you live in a Scandinavian country, you will be familiar with this taste and probably like it,” said neuroscientist and study co-author Emily Lehman of the University of Southern California.
Salted licorice has been a popular dessert in some northern European countries at least since the early twentieth century and its ingredients consist of salmiak salt, or ammonium chloride.
While scientists have known that the tongue responds in some ways to ammonium chloride, the specific protein receptors on the tongue that interact with it have remained elusive despite decades of extensive research.
The process became clearer when recent research revealed the protein responsible for detecting sour taste via a protein receptor in the tongue called OTOP1.
This protein is located within the cell membranes of the tongue and forms a channel for the transfer of hydrogen ions, a main component of acidic foods, into the cell.
Hydrogen ions are a major component of acids, and as food lovers around the world know, the tongue considers acid to be sour. This is why lemon juice (rich in citric and ascorbic acids), vinegar (acetic acid), and other acidic foods add a sour flavor when they hit the tongue. Hydrogen ions from these acidic substances are transmitted to taste receptor cells via the OTOP1 channel.
Since ammonium chloride also affects the concentration of hydrogen ions within the cell, the researchers wondered whether it could also stimulate OTOP1.
To study this, scientists inserted the gene behind the OTOP1 receptor into human cells grown in the laboratory so that the cells produced the OTOP1 receptor.
The team then exposed these cells to acid or ammonium chloride and measured the responses.
“We have seen that ammonium chloride is a powerful activator of the OTOP1 channel. It activates as well as or better than acids,” Dr. Lehman said.
Small amounts of ammonia from ammonium chloride were found moving inside the cell. Since ammonia is alkaline, it raises the pH resulting in a reduction of hydrogen ions.
The scientists explain that this difference in pH leads to the flow of hydrogen ions through OTOP1, which can be detected by measuring changes in electrical conductivity across the channel.
To measure this, the scientists used taste bud cells from normal mice and from genetically modified mice that do not produce OTOP1.
They measured how well taste cells generated electrical responses when ammonium chloride was introduced.
While taste bud cells from normal mice showed a sharp increase in action potentials after the addition of ammonium chloride, cells in mice lacking OTOP1 failed to respond to salt.
This confirms that OTOP1 responds to ammonium chloride.
The scientists also found that mice with a functional OTOP1 protein found the taste of ammonium chloride unappealing and did not drink water with added salt, while mice lacking the protein did not mind drinking the solution, even at very high concentrations.
“This was really the turning point,” says Dr. Lehman. “It shows that the OTOP1 channel is essential for the behavioral response to ammonium.”
The scientists also found that the OTOP1 channel appears to be more sensitive to ammonium chloride in some species compared to others.
Lehman suggests that the ability to taste ammonium chloride may have evolved to help organisms avoid ingesting harmful biological substances that contain high concentrations of ammonium.
“Ammonium is found in waste products, such as fertilisers, and is somewhat toxic, so it makes sense that we evolved taste mechanisms to detect it,” she explained, adding that more study is needed to understand the differences between species.