Searching for a second skin

By introducing a blood supply, Yale team overcomes some of the shortcomings of artificial skin.

Before the arrival of artificial skin in the 1970s, medical options for severe dermatological damage (widespread burns, blistering diseases, trauma wounds, extensive surgical excisions) ranged somewhere between scarce and nonexistent. Bandages and ointments were applied, followed by hopes and prayers that the patient’s skin, the only self-repairing organ in the body, would heal itself. The lifesaving options provided by artificial skin—human skin equivalents composed of everything from engineered porcine skin to skin from human cadavers—changed the face of dermatology.

Now, a Yale research team led by Jeffrey S. Schechner, M.D. ’91, assistant professor of dermatology, is on the verge of changing the face of artificial skin.

“[Artificial skins] were originally marketed as skin replacements, but in reality they functioned as biological dressings,” said Schechner. “They improve wound healing by some measurable amounts but they are not skin replacements.”

Schechner’s team, whose findings were published in The FASEB Journal, suspected that the reason these skin equivalents failed was that they did not develop perfusion—there were no blood vessels to allow blood flow after transplantation. The challenge, then, was to encourage vascularization in this artificial skin; that is, to replicate the mechanism of living skin tissue.

“Without a network of blood vessels, there is inadequate delivery of oxygen and nutrients in the critical posttransplantation period,” said Schechner.

The team’s experimental scaffold was acellular dermis (human cadaver skin), in which the cells are dead but a supportive matrix remains. This matrix was seeded with cells taken from the veins of umbilical cords which were modified to overexpress the gene Bcl-2, a modification that has previously enhanced blood vessel formation. (The Bcl-2 gene produces a protein that protects cells from enzymes that trigger cell death.) The matrix was then transplanted onto mice in Schechner’s lab.

It took more than two years of experimentation before Schechner had his eureka moment. “Within two weeks grafts that contained the Bcl-2 endothelial cells consistently developed blood vessels. ... and were perfused with mouse blood,” he said.

Further, these grafts held, and matured, over an eight-week period.

Schechner is quick to emphasize that theirs is “still an experimental model, not a clinical model.” Nonetheless, the potential benefit, if it does lead to a clinical product, will dramatically alter the role of artificial skin.

“This has been a huge area of research and clinical efforts for many in the field,” said Schechner, who is also chief of dermatology at the VA Connecticut HealthCare System in West Haven. “We all want the best way to dress [burn victims and surgical patients] and decrease the mortality and morbidity associated with these conditions.”

—Alan Bisbort

Increased risk of non-Hodgkin’s lymphoma linked to hair dye

WARNING: The prolonged use of hair dye, especially permanent black, brown and red, may be hazardous to your health. That’s the conclusion reached by Yale researchers in a study published on January 15 in the American Journal of Epidemiology. The scientists found that long-term users of hair-coloring products have an increased risk of developing non-Hodgkin’s lymphoma, a cancer that attacks the lymphatic system, part of the body’s immune system. “We found that people who used permanent dark hair dye for more than 25 years and started before 1980 will have more than twice the risk compared to people who never used hair-dye products,” said Tongzhang Zheng, Sc.D., associate professor of epidemiology and environmental health. Zheng said the study was prompted by an unexplained jump in the number of non-Hodgkin’s lymphoma cases in the last 40 years. In the early 1970s, there were about 10 cases out of every 100,000 people in the United States. By 1990, that number had increased to 19 cases. Today it’s still increasing in the United States and around the world.

The health risks of hair dye have been explored for years, but Zheng says previous studies have been contradictory and inconclusive. He and his research team conducted a six-year, case-controlled study of 601 Connecticut women between the ages of 21 and 84 diagnosed with varying subtypes of non-Hodgkin’s lymphoma. The women were asked about the type of hair coloring they used, the length of time they used the products and their age when they stopped. The study included a control group of 717 healthy women matched by race, age and other factors with the case group.

Researchers found the highest risk among users of darker permanent dyes, rather than among those who used semipermanent or temporary dyes. Zheng says that’s because darker dyes may contain higher levels of chemicals, and permanent dyes use an oxidizing process that creates new, potentially harmful chemicals.

The good news is that researchers didn’t find any increased risk of non-Hodgkin’s lymphoma among women who started using hair-coloring products after 1980. This could be because the contents of hair-dye formulas may have changed and become safer, or it could simply mean that not enough time has passed to evaluate the effects on this group. Zheng said further studies would have to be conducted to determine whether post-1980 hair dyes are indeed safer.

Noting that hair color is directly related to image—“how people are perceived and how they perceive themselves,” Zheng said that the study results need to be duplicated in different populations. Meantime, users of hair dyes should consider the trade-offs and alternatives, such as semipermanent dyes.

—Jennifer Kaylin

Et Cetera

Some vets better after 9/11

After the terror attacks of September 11, 2001, veterans with pre-existing post-traumatic stress disorder (PTSD) showed fewer symptoms—including nightmares, reactions to loud noises and numbness of feelings—than veterans admitted to clinics and hospitals in the previous six months and in previous years, according to a Yale study.

“Anecdotal reports from VA clinics suggest that some veterans, far from being overwhelmed by the horrific destruction, experienced feelings of familiarity, mastery and competence as survivors who had been exposed to horror in the past, but who had experience in coping with the resultant painful memories,” said Robert A. Rosenheck, M.D., HS ’77, professor of psychiatry and epidemiology and public health. His study was published last year in Psychiatric Services.

Although they were far from cured, these patients “seem to have benefited from the increased sense of community, patriotism and national pride across the country,” Rosenheck said.

—John Curtis

Cutting down helps smokers quit

Cutting down on the number of cigarettes smoked can help older smokers kick the habit, according to a Yale study.

“Most experts will say there is only one way to quit smoking and that is to stop smoking altogether,” said Tracy A. Falba, Ph.D., associate research scientist in the Department of Epidemiology and Public Health and lead author of the study, which was published in Addiction, the journal of the Society for the Study of Addiction. “Cutting down the number of cigarettes smoked, however, seems to promote quitting. Cutting down first may be an option for people trying to quit.”

The study used data from a national study of Americans between the ages of 51 and 61, but the concept could apply to smokers of any age, Falba said.

—J.C.


			Originally published in Yale Medicine, Summer 2004. Copyright © 2004 Yale University School of Medicine. All rights reserved.