Spray-on skin

Hard graft

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Surgeon Fiona Wood has pioneered a controversial treatment to reduce scarring in burns victims. Carina Dennis finds out how she counters her critics.

Fiona Wood is in a rush. Colleagues say she wants everything yesterday. A master of multitasking, she travels exhaustively and handles a hefty clinical and research load. It is this boundless energy and sense of urgency that drove the surgeon to develop a pioneering treatment to help burns victims.

Originally from Yorkshire, UK, Wood now heads a burns unit at the Royal Perth Hospital in Western Australia, where she has developed a technique called ‘spray-on skin’. It literally involves spraying a patient's wounds with their own skin cells, and works much faster than conventional methods. Wood says this speed helps minimize scarring and accelerates recovery.

Her method was put to the test under horrific circumstances in October 2002, when victims of the Bali terrorist bomb were flown to her unit. Her team worked around the clock, and managed to save all but three of the 28 patients who arrived. The incident propelled Wood into the media spotlight and she was named Australian of the Year 2005.

But fellow surgeons and scientists argue that her spray-on skin hasn't been proven to work. Unless it is subjected to rigorous clinical trials, it will never become accepted clinical practice, they say. Unfazed, Wood says her method is a key step towards scarless healing and will be useful in other routine surgical procedures, such as scar repair and cosmetic surgery.

“The day you stop being affected, is the day you should hang up your boots. Fiona Wood, Royal Perth Hospital”

Burns can be truly gruesome injuries. Without skin, the body weeps copious fluids and is dangerously vulnerable to infection. If a patient survives, they face living with disfiguring scars that tighten and restrict movement. Although Wood is very matter-of-fact when she talks about burns, she is still overwhelmed by the suffering of her patients, especially children. “The day you stop being affected, is the day you should hang up your boots in my opinion,” she says.

Tough challenge: several victims of the Bali bomb were given spray-on skin grafts by Fiona Wood (above). Credit: ROYAL PERTH HOSP.

How a burn is treated depends on the extent of the damage to the two layers that make up our skin. The upper epidermis contains keratinocytes, the cells that make keratin, which forms a tough protective sheath. The lower dermis is composed largely of cells called fibroblasts, which make collagen, giving skin its durability and elasticity. Shallow burns that singe the epidermis are left to heal on their own. But when the burn is deeper and more extensive, skin grafts are used. Thin strips of the patient's healthy skin are shaved off a donor site, taking mostly epidermis and a little dermis, and stretched over the exposed wounds. For severely burned patients, donor sites often need to be reharvested, but they usually take up to two weeks to grow back. An alternative is to use sheets of the patient's cultured skin cells, but these take three weeks to grow.

Treating severe burns is a race against time. “Seventy-five per cent of burn scarring remains permanent if it's not healed within 21 days,” says Wood. It also becomes a numbers game: the more burns there are, the less healthy skin there is available to harvest and cover the wounds. To buy time, surgeons can use coverings made from cadaver skin or manufactured sheets of foreskin cells. “But as these do not contain the patient's cells, they do not always result in permanent wound closure,” says Wood.

Driven to act

A key turning point for Wood came in 1990, when she was part of a team caring for a patient with severe burns. The group was experimenting with the then-new technique of growing sheets of skin cells derived from the patient. The cells had just begun to ‘take’ when the patient — who had survived for seven months — died from an infection that had invaded while her skin was missing. “I was overwhelmed by the thought that we had to be able to do better,” says Wood. “If we'd been quicker, the outcome might have been different.”

A few years later, she did do better. Wood recruited Marie Stoner, a cell biologist, and together they reduced the time for culturing a patient's skin cells from weeks to just five days. There was no magic, says Wood; rather, they simply whittled down the time to grow skin cells and sprayed them onto the burn using a syringe with a spray nozzle attached.

Wood's method — which she dubbed CellSpray — involves taking a skin sample about the size of a postage stamp, scraping off the keratinocytes and multiplying them in tissue culture for several days. The cells are then harvested and sprayed onto the wound1.

But CellSpray is not the whole solution. Wood often uses it in conjunction with traditional grafts. Keratinocytes need a healthy underlying dermis as an anchor point and source of nutrients. So if the burn has damaged or destroyed the dermis, Wood uses a skin graft before spraying it with the cultured cells. If the dermis is lost completely, it first has to be rebuilt using either a much thicker skin graft or an artificial protein scaffold into which fibroblasts and other cells migrate. After a few weeks, the epidermis can then be added over the top by grafting as well as spraying.

Fiona Wood hopes to find a way to heal wounds without leaving scars. Credit: ROYAL PERTH HOSP.

CellSpray was first used on patients in 1995 and has been routinely deployed in Wood's burns unit ever since. She is adamant that it leads to faster healing and reduces scarring. It also requires fewer donor sites — particularly useful for severely burnt patients.

But Wood's peers are sceptical. Peter Haertsch, head of burns and reconstructive surgery at Concord Hospital in Sydney, Australia, says it's a brilliant idea but argues that there is not enough evidence that it works.

Haertsch is strongly critical, even though he is experimenting with the technique in his own unit. But he is not alone — the burns specialists interviewed for this article agreed that randomized clinical trials are needed. There is also some doubt over whether the spray-on cells fall off over time. For this reason, Haertsch says it's unclear how much the spray actually contributes to wound healing compared with the underlying skin graft and cells migrating in from surrounding tissues.

But Wood believes her results speak for themselves. “The evidence is borne out by experience,” she says. She and her staff are convinced that patients suffer significantly less scarring thanks to the technique. As a result, she feels it would be unethical to do clinical trials in which some patients get spray-on skin whereas others get conventional grafts. Furthermore, it is difficult to compare burns treatments because of the variability of the wounds.

Wood has published some results using spray-on skin in animal models2,3, but she acknowledges that she won't convince her peers without clinical trials and has helped to design a multicentre randomized trial to be conducted in Australia and internationally. This will involve patients who have burns to more than 20% of their body. Each patient will receive traditional skin grafts on one side of their body and spray-on cells plus a skin graft on the other side. Wood and her team are conducting a complementary study in which they are comparing the outcomes for their patients with those at other units who have received conventional treatment.

While experts ponder its value, Wood has ambitious plans for CellSpray. She thinks it could also be useful for minimizing scarring in routine surgical procedures such as repairing birthmarks or removing moles. A kit for the method, called ReCell, is being distributed by Clinical Cell Culture, a company that Wood co-founded in 1999. It has been submitted for approval by regulatory agencies including the US Food and Drug Administration and its Australian equivalent, the Therapeutic Goods Administration, and has recently been approved for clinical use in the European Union and Japan.

Reluctant entrepreneur

Wood says that commercializing her work has been an “educational experience” but adds that she doesn't feel comfortable in the role. Rather, she sees it as a means to raise funds for the non-profit McComb Foundation, which supports burns research using her company's profits.

Ultimately, Wood wants to achieve healing without scars. She is now trying to combine the reconstruction of the dermis and epidermis into a single step. To do this, she sprays keratinocytes onto Integra, an artificial scaffold derived from shark cartilage and cow collagen. This is then applied to the wound, where the dermal cells move into the scaffold to regenerate the dermis, and the keratinocytes migrate to the top to rebuild the epidermis. Wood's team claims success with a mouse model and hopes to test the technique in patients soon.

The team is also trying to improve artificial scaffolds and is using three-dimensional scans to build a picture of skin topography, burns and the healing process at different sites of the body. The ultimate goal is to use computer technology to scan patients and predict the best treatment for different burns. Wood adds that this will help to quantify the outcome of her treatments, and hopefully appease her critics.

Although she is an enthusiast of basic research, Wood's clinical pragmatism never subsides. “It might be nice science, but I need to be able to use it,” says Wood. And the sooner, the better.

References

  1. 1

    Wood, F. M. Wounds 15, 16–22 (2003).

  2. 2

    Navarro, F. A. et al. J. Burn Care Rehabil. 21, 513–518 (2000).

  3. 3

    Navarro, F. A. et al. J. Burn Care Rehabil. 22, 41–46 (2001).

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Author information

  1. Carina Dennis is Nature's Australasian correspondent.

    • Carina Dennis

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Dennis, C. Hard graft. Nature 436, 166–167 (2005) doi:10.1038/436166a

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