Clinical trial of artificial skin for severe burns begins at Melbourne's Alfred Hospital

Shiva Akbarzadeh, dressed head to toe in a hairnet, mask, gown, gloves and shoe covers, gestures at the lab around him.

“This is where the magic happens,” she says.

On this particular day, no magic happens. The device is switched off. Contains pipettes, flasks, and other laboratory equipment.

But when things accelerate, they really accelerate.

That's because in this room at Melbourne's Alfred Hospital, Dr Akbarzadeh and his research team at Monash University are creating squares of artificial human skin.

The machine, which currently sits quietly on a laboratory bench, will be working non-stop for weeks on end. Researchers tend to live cells submerged in nutrient-rich cultures under what is essentially the buzzing drone of an industrial range hood.

this The team is conducting clinical trials The safety and effectiveness of artificial skin will be tested on people with severe burns covering at least 20 percent of their bodies.

When trial participants arrive, researchers take a small sample of healthy, unburned skin and use it to grow billions of new skin cells in a lab incubator.

These cells are suspended in a sheet of strong, flexible hydrogel and surgically implanted into the patient.

Although it is too early to report long-term results, they have so far used their latest artificial skin on adults and children.

“Most wounds closed within two weeks, with little sign of early scarring.”

Her lab is one of a few across the country working to create artificial skin that helps deep burns heal quickly while providing patients with the best quality of life possible.

And they continue Australia's long history of burn research and technology, now used on operating tables around the world.

When traditional porting is not possible

How well a burn heals depends on many factors, including a person's health, age (older people heal less quickly than younger people), and the size and depth of the burn.

• Superficial burns (also called first-degree burns) affect only the outermost layer of the skin or epidermis.
• Partial thickness burns, or second-degree burns, also damage the second layer of skin called the dermis.
• Full-thickness or third-degree burns are the most serious. It burns through the epidermis and dermis to the underlying muscle, bone, or fat.

Small or superficial burns usually heal within a few weeks, but this is not the case for large, deep burns. Even if it does heal, it heals incredibly slowly. This means that people with extensive burns are also at a much higher risk of infection.

The most standard treatment for most severe burns is to remove a thin layer of skin from an unaffected area of ​​the body (usually the epidermis and part of the dermis) and surgically graft it onto the burn site. It is to do.

Because it is the patient's own skin, known as an “autograft,” it is less likely to be rejected than skin donated by someone else.

For further elongation, the autograft can be perforated or “meshed.”

However, even if the wound is closed with an autograft, the skin is prone to scarring. Heather Cleland, a reconstructive plastic surgeon at The Alfred Hospital, said this can affect a person's daily life and limit movement, especially if it's in the face or joints.

“In the process of treating burns and trying to heal these patients, we routinely perform skin grafts from areas that were not burned. So we create a second wound if necessary, and This will cause more damage to the patient's skin.”

This can be a serious problem for older people, who don't recover as easily as younger people.

Also, if large parts of the body have been burned, an autologous transplant may not be possible at all.

So researchers are working on ways to reduce or eliminate the need for autologous transplants by creating more skin cells from just a few.

Lab-grown skin recipes

Perhaps the most well-known cell therapy for burn injuries is the technology developed by ReCell. Australian surgeon and burn specialist Fiona Wood and her collaborator Marie Stoner, who created “spray-on skin” more than 30 years ago.

It works like this: A small piece of skin taken from a patient on the operating table is placed in an enzyme cocktail, which breaks down the skin into cells. This is similar to how a brick wall is broken down into individual bricks.

A cell-rich liquid is then sprayed throughout the cleaned wound, where the cells begin rebuilding the dermal and epidermal skin layers, accelerating the healing process.

Spray skin can be used in conjunction with traditional skin autografts, and alone in partial thickness burns. However, for large and thick people, Surgeons with burn injuries where harvesting autografts is not an option need something a little more rugged.

This is where artificial skin sheets can be expected.

Skin engineering laboratories around the world use almost the same technology to create “skin.” A small sample of healthy skin is taken from a patient, the cells within the sample are encouraged to generate more of their own, and then suspended and transplanted onto a sheet.

However, although this seems relatively easy, it is not.

One of the issues with artificial skin is angiogenesis. This means that the body's blood vessels can rapidly grow within the graft to provide nutrients to the cells inside.

Dr. Akbarzadeh's hydrogel sheets, which are embedded with skin cells grown in a patient's lab, cannot be used for blood transfusions because they are made from expired platelets provided by Life Blood Services, but they can be used for research.

She says that platelet-rich hydrogels not only hold skin cells in place, but also “have inherent antimicrobial properties and promote angiogenesis.”

Another issue is time. It takes four to six weeks, not to mention a lot of human labor, to create enough skin cells for a manufactured graft.

In the meantime, the surgeon will cover the deep burn with a synthetic bandage called a “biodegradable temporary matrix” (BTM).

it's an invention Emerged from CSIRO in early 2000Joe Mites, a surgeon and head of the burn and reconstructive surgery research group at Sydney's Concord Hospital, says it is now being used on surgeons' tables around the world.

“This was a game-changer in the world of burn surgery.”

The BTM acts like the dermis and buys time until the artificial skin is generated. The graft can then be placed directly over the BTM bandage, but the bandage will eventually break down.

Bronwyn Dearman, Chief Medical Scientist at the Royal Adelaide Hospital's Dermatology Laboratory, is no stranger to BTM development.

She and colleague John Greenwood carried out research to improve the material developed in Adelaide.

Recently, part of her lab's research program has been “cultured composite skin.”

Ideally, surgeons want large sheets of artificial skin, says Dr. Dearman: “If there are small pieces, it can leave a patchwork quilt-like appearance.” [on the body] The application will take more time. ”

So, as part of her Ph.D. research, she Cultured composite skin 25cm square.

In 2018, the laboratory Cultured composite skin was used on the limbs and chest of a 32-year-old man He came to the hospital with burns on 95 percent of his body.

After a few years, the man lives independently.

Dr. Dearman and her team are currently refining the composite skin process.

“Our ultimate goal is to reduce the use of autologous skin grafts,” she says.

When will artificial skin become widely available?

The ability to create tailored skin grafts quickly and inexpensively has implications not only for burns, but also for other types of chronic wounds, such as diabetic foot ulcers.

Concord Hospital's burn and reconstructive surgery group, which established a skin biobank to accelerate research, is looking at ways to not only generate cells faster, but also reduce complications associated with scarring.

In most wounds, long, thin cells in the dermal layer contract to draw the edges of the wound together. Once the overlying epidermis has fully grown and closed the wound, the contracting cells receive signals from their surroundings and die naturally.

However, in the case of a burn injury, the cells that are contracting do not receive the message. They keep pulling. And that means many people who sustain burns are left with thick, raised scars called hypertrophic scars, Dr. Mitz says.

To combat this, Dr. Maitz and her colleagues are investigating the use of Botox, which “can reduce the activity of certain cells that cause hypertrophic scarring.”

Then there are other ways to improve burn healing, such as cellular “rejuvenation.”

Young skin stem cells multiply faster than older stem cells, so finding a way to turn back the molecular clock could allow artificial grafts to be transplanted more quickly to people who need them.

This research and much of the research in other labs is still in its early stages.

So while clinical trials of artificial skin look promising, we still have a ways to go before such grafts are completely indistinguishable from the skin that people typically grow on their bodies.

“Every skin laboratory in the world is working on the holy grail of creating skin that is functionally and physiologically viable, with pigmentation, hair follicles, and sweat glands,” says Dr. Dearman.