Bioengineers working toward bioprinting skin for laboratory testing may be part of the answer for clinicians interested in a solution that’s easier on patients for covering severe burns with new skin.
In 2015, at least three companies enlisted the help of bioengineers to develop bioprinted skin that could be used for testing cosmetics and consumer preparations, a step that holds promise for testing pharmaceuticals as well.
The three companies are: cosmetics and skin care company L’Oreal (New York), teamed up with human tissue model maker Organovo (San Diego); Procter & Gamble (Cincinnati, OH), the American consumer products manufacturer, offered $44 million in grants to researchers in Singapore; and chemicals manufacturer BASF (Ludwigschafen, Germany) started work with bioprinting company Poietis (Pessac, France) to further develop its skin model, Mimeskin.
All three partnerships hope their work will result in skin that comes off a printer, which could ultimately replace the autologous skin grafts and temporary measures that burn specialists now employ.
“Honestly, I think it would be a game changer, especially for large burns,” says Dr. Amy Spencer, co-medical director of the burn unit at Spectrum Health System in Grand Rapids, MI.
Several developments should give Spencer and her patients encouragement. Consensus among many bioengineers is that skin is the easiest organ to print. Their biggest challenge – and, frankly, Spencer’s and others who do autologous transplants – is vascularization.
Another factor that should inspire hope is the move away from animal testing for new drugs and cosmetics, which provides the motivation to bioengineer skin. Such testing is banned in the European Union, as is marketing of products made elsewhere that were tested on animals.
There’s a lot at stake for Spencer, her patients, and others.
The World Health Organization estimates there are 11 million burns annually worldwide that need medical attention, according to 2004 data. In 2015 in the United States, 486,000 burn injuries received medical treatment, according to the American Burn Association.
State-of-the art treatment for burns by Spencer and other doctors includes shaving a thin layer of skin, up to .12mm (.005in) thick, typically from a patient’s back or leg, and stapling, stitching or gluing it to a burn site. Their work leaves a “stinging, bleeding wound” that takes up to a few weeks to heal, Spencer says.
That’s in a good situation, where an autologous skin graft is possible. “What you run into with people with large burns, you may not have a good donor site,” Spencer adds.
Pig and cadaver skin are stopgap measures used to protect burn wounds from infection, but so far there is no permanent replacement for a person’s own skin.
“You can’t say O.K., I’ll go out and buy a bucket of cells,” says David Wallace, vice president at MicroFab Technologies (Plano, TX), experts in ink-jet printing. “Using them (cells) very conservatively is what we see as the advantage in inkjet printing.”
While no biologist, Wallace knows what he’s talking about.
MicroFab worked with the Wake Forest Institute for Regenerative Medicine (Winston-Salem, NC) to develop a dermal repair construct printer for research. MicroFab’s inkjet printing platform family includes a group of devices that allow for printing a wide variety of necessary materials, including polymers, sensitive protein solutions, tissue extracts and live cells. In addition, the devices can be heat sterilized or gamma irradiated without damaging them.
Wake Forest has tested its work on animals so far with good results in appearance, stability and vascularization, says John Jackson, associate professor of regenerative medicine.
“A small skin biopsy is taken from a non-injured site and the keratinocytes and dermal fibroblast are expanded in culture,” says Jackson in explaining Wake Forest’s method. “These expanded cells are then placed in the skin bioprinter and printed in layers on the wound area.”
Jackson and his colleagues use a laser scanner to determine the configuration of the burn wound.
In Europe, Ingmar van Hengel and his company, SkinPrint, are also working to develop bioprinted skin.
Van Hengel and a group of fellow students established SkinPrint (The Hague, Netherlands) when they were undergraduate students at the University of Leiden. They subsequently teamed up with Ernst Reichmann, leader of the EuroSkinGraft initiative at the University of Zurich to work in his lab.
“We’re optimizing our process and doing pre-clinical work,” says van Hengel, who’s currently working toward a bioengineering degree at the Delft University of Technology. “Our idea is to print all layers of skin.”
Meanwhile, the Food & Drug Administration is fast-tracking another “engineered” skin technology that originated in Australia and is already in use there, as well as China and Europe, that would benefit burn patients and others. The skin technology uses the body’s own bioreactor properties to regenerate skin, and may offer insight to engineers intent on printing skin.
Avita Medical (Northridge, CA) recently finished enrollment in Phase 3 clinical trials for ReCell, its technology that uses autologous samples to encourage skin growth to heal burns and chronic wounds like diabetic skin ulcers, and to treat pigmentation conditions like vitiligo – the same clinical uses envisioned for bioprinted skin. A sample that undergoes ReCell’s chemical and mechanical processes contains all four types of skin cells – keratinocytes, fibroblasts, immune system cells and melanocytes – and can cover an area 80 times its size, up to 24cm2 (3.7in2).
The technology borrows from skin cell culturing.
“What the inventors of ReCell found is that culturing is time consuming, expensive and fraught with issues, but the wound bed is a magnificent site for culturing skin,” says Andrew Quick, Avita’s Vice President of Research & Technology. “ReCell leverages what the body is programmed to do anyway.”
Aside from the FDA, Washington helped fund Avita’s late-stage clinical development and wants to buy more than 5,000 of its devices for a mass casualty preparedness program to treat burns.