Skin: Advanced Dressings, Cultured Skin

by Food and Drug Administration (FDA)

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Advanced Dressings

FDA recognizes two broad categories of wound dressings — interactive and noninteractive. A variety of noninteractive dressings are available for covering first- and second-degree burns and other wounds. An interactive dressing is intended to actively promote wound healing by interacting directly with body tissues. Manufacturers must submit safety and effectiveness data to FDA in a premarket approval application. FDA has approved two interactive wound dressings for use on third-degree burns: Integra Artificial Skin and Original BioBrane (Blue Label), marketed by Dow B. Hickam, Inc., New York.

BioBrane is a knitted nylon fabric bonded to an ultra-thin silicone rubber membrane coated with a protein (gelatin) derived from pig tissue. Clotting factors in the wound interact with the gelatin in the dressing, causing it to adhere to the wound within a day or so. The dressing remains in place until autografting becomes possible.

Integra is a two-layer membrane — a dermal layer that's a porous lattice of cross-linked collagen fibers, and a synthetic epidermal layer. The dermal layer acts as a biodegradable template that helps organize dermal tissue regeneration. Fibroblasts and other cells migrate into the lattice from surrounding healthy tissue, as do blood and lymph vessels. The fibroblasts degrade the temporary scaffold and recreate their own collagen matrix.

"The dermal part of the product is a permanent cover which the body converts into something which looks more like dermis than it looks like scar tissue," Heimbach says.

The outer synthetic layer provides the barrier functions of epidermis for two to three weeks; then the surgeon replaces it with a very thin autograft. "The ability to have the donor site be very thin and heal in just a few days is the big benefit," says Kaplan. "You're actually adding a procedure, but the end result is positive."

"It's a neat concept and it appears to work," says Heimbach, who has used Integra on more than 100 patients during clinical trials. He says the final results look much better than the alternative, meshed autografts. "We're excited about the new composite skin substitutes," he says.

Cultured Skin

Doctors prefer a thin graft to a thick one, but eliminating the donor site wound and scar altogether would be even better. That's done by growing the patient's skin in the lab, under special tissue culture conditions. Lab-grown skin products also have other potential uses for wounds other than burns, and for laboratory testing. (See accompanying articles.) From a postage stamp-sized piece of skin, technicians can grow enough skin in about three weeks to nearly cover the body. Some medical centers are equipped for this sort of cell culture, and Genzyme Tissue Repair, Cambridge, Mass., does it as a commercial service. Cultured skin has been available for treating burns for about a decade, and in certain circumstances it can work well.

"The problem here is you're putting on epidermis and not dermis," Kaplan says.

"Without both parts, you don't really have skin," Heimbach says. "You're grafting on scar tissue and that's not a satisfactory skin covering."

Less than 10 cells thick, it's also tricky to handle. "It's like gossamer," Kaplan says. And something has to cover the wound in the meantime. That's where Kaplan and others see a potentially useful combination. The patient's epidermis could be cultured during the two to three weeks while Integra's dermal layer becomes a suitable bed for grafting. "They're complementary," says Kaplan.

"You'd have the best of both worlds. You don't have any donor sites, and you have a good, durable, cosmetically acceptable cover," says Heimbach.

"Another approach we're actively working on is the one-step procedure," says Frederick Cahn, Ph.D., senior vice president, technology, Integra LifeSciences. The patient's own epidermal cells are isolated, as they would be for culturing, then seeded onto the dermal layer of Integra before it is applied to the wound. Both skin layers regenerate in place simultaneously, and only one surgical procedure is required. This procedure has worked well in animals, but hasn't been tried in humans yet.

Although physicians welcome new ways to help their patients, they're leery of "scar in a jar" products that might solve some problems while creating others. Last year, FDA held hearings on using the patient's own cells for structural repair in therapy, and heard a strong call for measures of efficacy. Based on the testimony presented, FDA has decided to regulate such therapy and is developing guidance documents to assist manufacturers in completing the premarket review process.

"FDA recognizes that the area of tissue substitutes is a rapidly evolving area — and that medical and biochemical practice are also growing rapidly — and it's working aggressively to make sure it doesn't stifle development while continuing to ensure patient safety," says FDA's Durfor.

Investigators have developed other variations on cultured skin in the hope of providing off-the-shelf, living, temporary or permanent dressings. Clinical trials are under way testing them on burns and other wounds. For example, Advanced Tissue Sciences, La Jolla, Calif., developed its Dermagraft-TC skin replacement to be used as an alternative to cadaver skin for burns.

Treatment for burns keeps improving, but burn surgeons still have another important concern. "I think 95 percent of the burns we see are completely preventable," says Heimbach. He credits smoke detectors for a huge drop in the number of burns and deaths from house fires, but he hasn't seen much change in the number of accidents caused by carelessness or ignorance.

"The answer to the burn problem is prevention. Once it happens, it's too late," Klein says. "Be careful so you never need us."

About the Author

www.fda.gov
FDA is A United States government body that oversees medical devices, including contact lenses, intraocular lenses, excimer lasers and eyedrops. In the US, these products must be approved by the FDA before they can be marketed.