6 minute read
Johan Junker, Region Östergötland
AIMING TO PRODUCE SKIN THAT FUNCTIONS
Severe burns are today treated with grafts that restore the skin’s role as a barrier, but other functions – including sensitivity, temperature regulation and elasticity – are lost. Johan Junker and his colleagues hope to remedy this.
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The skin is our largest organ and provides a protective barrier against the outside world. Current methods of treating major wounds, such as burns, generate hard and ugly scarring and the sensitivity, temperature regulation and elasticity of normal skin is lost – which is why researchers Johan Junker, associate professor of plastic surgery, and Daniel Aili, a professor in the biophysics and bioengineering division at Linköping University, want to create better skin to transplant. Johan Junker says they complement each other well.
“Daniel and I have very different skillsets – he’s an engineer, and engineers are extremely clever,” says Johan Junker. Daniel Aili adds:
“But we have a tendency to complicate things when we get fascinated by a technical solution. That’s when it’s good to have Johan bringing us back to reality,” he says.
“I find applications for things – ‘you’ve made a great biomaterial and now I’m going to cut it up with scissors and put it on a wound’,” chips in Johan Junker as an example.
A damaged skin barrier can result in wounds that are difficult to heal, commonly known as ulcers. The RiksSår quality register defines these as wounds that have not healed within six weeks. Johan Junker says these are both the most common and the most expensive problem in healthcare. “Between 25 and 40 percent of all hospital beds in the EU are occupied by patients with slow-healing wounds. In Sweden 4 percent of the entire healthcare budget is spent on treating these – the single largest item in the budget,” he says.
For those affected, too, the consequences can be huge.
“It may be that a person has to organise their life around going to the clinic two or three times a week to have their dressing changed,” says Johan Junker.
The project ‘Skin biofabrication and transplantation for the treatment of burns’ focuses on wounds resulting from burns. These are currently treated using skin grafts, which involves planing off a thin layer of healthy skin from the patient and moving it to the damaged area. But although the wound is closed, scarring results.
“Scarring over joints or hands can result in reduced mobility,” says Johan Junker.
It is also possible to cultivate skin cells from the epidermis, the skin’s outer layer, but applying these to a fairly deep wound again results in scarring. Now the researchers hope to be able to produce functioning skin to transplant by combining two different tracks.
One element involves what are known as micrografts – taking small pieces of skin and growing them on.
“The advantage is that we then have different kinds of cell types with the interaction between them that exists in actual skin. So far we have been able to use such micrografts to expand skin up to a hundred times, which means that a piece the size of a postcard could be sufficient to cover the entire body,” says Johan Junker.
A 3D bioprinter is used to combine biomaterials with cells. This enables the researchers to produce tissue of a specific shape and size.
They have published this previously in the journal Plastic and Reconstructive Surgery. The second element is Daniel Aili’s specialism and involves printing skin using a bioprinter.
“It works like a normal 3D printer, but instead of printing in plastic we use cells embedded in a hydrogel,” he says.
This is a challenge, since the cells are highly sensitive and can easily be broken and die. The material printed along with the cells both protects them and acts as a stabilising three-dimensional polymer network that can help the cells to start forming tissue-like structures. The researchers have succeeded in creating these, as they published in Biofabrication in 2020.
“Here we will explore the possibilities of printing multiple layers of cells and combining various relevant cell types, micrografts and materials that stimulate the formation of new skin,” says Daniel Aili.
In collaboration with colleagues in Gothenburg the resulting skin will be tested on mice to see that it works and is not harmful. In a next step the skin material will then be tested on pigs, where wound healing is similar to that of humans.
“As with us, the skin is attached firmly to the underlying layer – in contrast to rodents, where the skin is loose. They heal wounds by puckering the skin together. We will try covering both regular wounds and burns with the material,” says Johan Junker. The hope is that the new skin material that the project generates will be able to be used for burns, but also for other wounds that are slow to heal. In an earlier study published in Burns in 2020 they were able to show that small pieces of gelatine that were covered with two cultivated cell types were able to heal wounds on pigs.
The importance of the support from the ErlingPersson Foundation cannot be overstated, the researchers say.
“To put it bluntly, we would not have been able to do this without funding – so the support is 100 percent essential for this project. We’ve already started bringing in doctoral students and postdocs who will work on various elements,” says Johan Junker.
Daniel Aili adds:
“We also hope that the project will give rise to new ideas and to younger colleagues learning more about this area, so that the knowledge spreads out like rings on water.”
25–40%
The proportion of hospital beds in the EU occupied by patients with slow-to-heal wounds. In Sweden it is estimated that 4 percent of the entire healthcare budget is spent on such wounds.
2–3
In 2–3 weeks the epidermis is replaced across the entire body. Johan Junker says that most ends up in bedclothes.
100
How much the researchers have been able to expand skin to date. It means a piece the size of a postcard could be cultivated to cover the entire body.
ABOUT THE PROJECT Project managers: Johan Junker, associate professor of plastic surgery at the Laboratory for Experimental Plastic Surgery and coordinator for experimental traumatology at the Centre for Disaster Medicine and Traumatology, Linköping University, and Daniel Aili, a professor in the Biophysics and Bioengineering division at Linköping University.
Title: ‘Skin biofabrication and transplantation for the treatment of burns’.
What it involves: Being able to produce skin material that is more like real skin, for treating burns. One element involves cultivating skin from micrografts. The other is to use a bioprinter to print skin consisting of multiple cell types in various layers, supported by a kind of three-dimensional grid.
Funding: The Erling-Persson Foundation is supporting the project with a total of SEK 8 million over three years.
