Searching for a second 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.”