There’s no good way to get rid of scarring, but that might be about to change
By TRACIE WHITE
When Geoffrey Gurtner worked as a surgery resident at Boston Shriner’s Hospital, he regularly treated children with disfiguring burns over their faces and bodies. These young patients would undergo 60 to 70 operations and, in the end, still look horrendous.
“As surgeons, we can save their lives,” says Gurtner, MD, now associate professor of surgery at Stanford’s medical school. “But we can’t save the quality of their lives. These kids live diminished lives for an injury that is literally only skin deep.” The memory of these patients has haunted him over the years, sending him from the operating room into the research laboratory looking for answers. “The scalpel was obviously not the answer,” he says.
Now, after six years of laboratory research building on an insight from his surgical patients, Gurtner has made the first real step toward meeting his goal of discovering how to reduce or, someday, eliminate scarring altogether. “I’ve finally hit on something,” Gurtner says.
In a study published online this summer in the journal FASEB (Federation of American Societies for Experimental Biology), Gurtner and colleagues reported their new insights into the pathophysiology of scarring. It’s the first step in a multidisciplinary attempt at Stanford to battle disfiguring scarring — dubbed “Scar Wars” by one researcher.
Gurtner predicts that new therapies to significantly reduce scarring are only a year or two away. And the project has already provided the first animal model for scar research.
Burn patients desperately need new treatments, says Kevin Cook, an activist for burn research and a patient at the Santa Clara Valley Medical Center in San Jose. Cook suffered burns over 85 percent of his body in 1997 when diesel fuel spilled on him and ignited during a welding job.
Cook has had 50 operations, which have not significantly improved the disfiguration from the burns, he says.
More than a superficial problem
“I’ve had both eyes, my nose, my mouth, my ears operated on. My hands are constantly getting worse and worse. My mouth got to the point where I could barely fit a teaspoon of sugar through. My nostrils got so small I couldn’t fit a Q-tip through,” Cook says. “And every time you have surgery, it knocks you down.”
Yvonne Karanas, MD, is a member of Gurtner’s Scar Wars team and director of the burn center at Santa Clara Valley Medical Center. “I’m waiting with bated breath for solutions,” says Karanas, who is also clinical assistant professor of surgery at the medical school. She points out that in addition to suffering permanent disfigurations, her burn patients often endure lifelong limits on function that leave them unable to close their eyes or mouths because of scar formation.
“Right now, there are no good solutions,” she says. The endless surgeries can help somewhat with function, Cook says, but the permanent disfigurement is life changing, especially for patients with facial scars.
“Your face is who you were. That was your identity,” Cook says. “To lose your identity is a big factor.”
The FASEB study began with the premise that if you apply mechanical stress to a wound — if you exert pressure by pulling, pushing or stretching on the skin — you make the scarring worse. This is common knowledge among surgeons, like Gurtner, who deal with skin and scarring on a daily basis, but not so among scientists in general.
“Surgeons know that, of course, tension is bad for wounds,” says Michael Longaker, MD, the Deane P. and Louise Mitchell Professor in the School of Medicine, a stem cell biologist and expert in fetal surgery, and one of the study’s authors. “Actually proving it is another thing. This paper nails it down.”
Researchers chose mice to test their theory because mice, in general, don’t scar. Small mice, like human fetuses, heal with little or no scarring.
“Size matters,” Gurtner explains. Larger animals with bigger muscles and greater tension in their skin overall have thicker scarring. “The mechanical force on mice is about one-tenth of that on humans. When you get to whales, they’re actually identified by their scar patterns.
“The more mechanical stresses on the skin,” he says, “the more promotion of scar formation.”
The study’s authors hypothesized that if the same amount of mechanical stress were applied to a mouse wound as is naturally exerted on a human wound, human-like scars would form in mice. To test this, they created a device that exerted mechanical pressures on the mouse equivalent to that exerted on humans.
As expected, the mice developed large human-like scars as the wounds healed. “Without an animal model for thick scars, our ability to develop targeted therapies has been severely limited,” says Longaker. “Now we have a model.”
The study points out that the scarring in these mice happened during a brief, seven-day period immediately after the wound occurred, indicating a critical time period exists early in the healing process when therapeutic treatment would be most successful.
By controlling the physical environment of a wound in humans, it might be possible to change the way the skin heals, the study concluded.
Gurtner has gathered a team of researchers from Stanford’s schools of medicine and engineering in fields ranging from dermatology to structural engineering to design future therapies.
“This research really looks at the core of why these scars develop,” Karanas says. “If we can prevent it from happening, it’s a lot better than trying to treat it once it’s developed.”
Some of the team’s research involves investigating the structural differences in embryonic skin and adult skin. Scientists have known for decades that a fetus can heal without scarring. Gurtner’s latest research might lend new light on why.
“Fetuses live in a very unloaded mechanical environment,” Longaker says, referring to a mother’s womb. “There are almost no forces, no stresses. Maybe by creating a similar environment, we can reduce scarring.” The team has drawn in Reinhold Dauskardt, PhD, a world expert on skin mechanics and professor of materials science and engineering, to help investigate the problem.
“It turned out a lot of the work we’re doing in our engineering department on the mechanical function of skin is very relevant when considering skin healing,” Dauskardt says. “If we can control the mechanical environment of skin, we can attempt to create the optimal environment to prevent wound scarring.”
Stem cell research in the area of skin regeneration also features prominently in the team’s research, with the hope that stem-cell therapies would someday eliminate scarring. Gurtner has applied for a grant from the Armed Forces Institute of Regenerative Medicine to fund research into decreasing scarring and promoting regenerative healing in injured soldiers.
“Let’s assume that it’s not OK to heal with scars,” Longaker says. “No one is happy with scarring. How about no scars at all?”
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