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It may be hard for a healthy person to imagine having a wound that just won't heal, but that problem plagues millions of Americans. Nonhealing wounds not only take an emotional toll, but also leave patients, their families, and society with a serious economic burden, ranging into billions of dollars.

The incidence of chronic wounds is far greater than burns and is expected to continue to increase as the population ages. Some of the treatment concerns are similar because the barrier function of skin is lost, putting the patient at risk for infection, and chronic wounds can be life threatening.

There are three general types of chronic wounds: pressure ulcers (bedsores or decubitus ulcers), venous ulcers, and diabetic ulcers. They have different causes, but the result is the same — localized tissue death. The factors that cause an ulcer to develop in the first place also interfere with healing. The cost per healed ulcer — when they heal at all — can climb into the tens of thousands of dollars, and as many as half recur within a year. Roughly three-quarters of a million American diabetics suffer with foot ulcers, which are responsible for more than 50,000 amputations a year.

Recent research efforts in pursuit of various growth factors to promote wound healing have been disappointing. Figuring out which growth factors to put in a wound — and when and at what dose — is a daunting, perhaps impossible, task. Some investigators have turned to cultured skin, arguing that applying cultured skin to wounds makes more sense than using growth factors because living cells already know how to produce growth factors at the right time and in the right amount.

Organogenesis Inc., of Canton, Mass., has developed Apligraf (formerly Graftskin), a two-layer living skin substitute derived from infant foreskins. The upper layer contains keratinocytes, the dominant cell type in the epidermis. The lower layer contains collagen and fibroblasts, the main constituents of dermis. Other cell types that trigger immunological response are absent, and, as a result, this engineered tissue is not rejected. Human trials of Apligraf for treating burns, diabetic ulcers, and for use in other skin surgeries are under way.

Cultured skin offers new hope for chronic wounds, but, as with burns, prevention is the best bet.

Skin Under Glass

In addition to its potential as an advanced wound dressing, cultured skin may also prove useful in laboratory testing. Many cosmetic, household product, pharmaceutical, and petrochemical companies are experimenting with cultured skin in the hope that in vitro (in glass, meaning in lab vessels) assays can replace or reduce animal testing for evaluating raw materials and final product formulations. FDA has long supported development of such methods, but the state of the science hasn't progressed yet to where it can fully replace animal testing, according to FDA's John Bailey, who heads the Office of Cosmetics and Colors in the agency's Center for Food Safety and Applied Nutrition.

Scientists can use isolated skin tissue to test skin penetration, irritation, toxicity, and other effects of various substances. Although cadaver skin works for some purposes, its uses are limited because the cells are dead. Cultured skin contains live, metabolizing cells that can better mimic how skin responds to various stimuli.

One example is the EpiDerm System, a model of human epidermis marketed by MatTek Corp., Ashland, Mass. Human-derived epidermal cells are grown under culture conditions that encourage formation of the characteristic cell subtypes and layers of epidermis. Another example is Skin2 , developed by Advanced Tissue Sciences, Inc., La Jolla, Calif. Some versions of Skin2 contain dermis as well as epidermis. These products are intended to be used for testing, not as dressings.

Lab-grown skin is used in two general ways. As a membrane to measure skin absorption, it doesn't work very well because it's much more permeable than skin, according to Robert L. Bronaugh, Ph.D., chief of the skin absorption and metabolism section in FDA's Office of Cosmetics and Colors. "A lot more work needs to be done before it can be used to simulate accurately the barrier properties of human skin," he says.

However, as an alternate test to measure irritation, cultured skin looks encouraging, according to Bronaugh. The U.S. Department of Transportation has approved the use of a Skin2 in vitro test kit as an alternative to animal testing of potentially corrosive materials. Although FDA wouldn't accept final safety data acquired from these in vitro assays, companies can use cultured skin in early screenings, and that saves animals, as well as money.

Tags: Skin Care

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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.