Only skin deep

Due in part to their simple structure, skin substitutes and cartilage replacements were the first engineered tissues to reach the market. One of these early products is TransCyte, the burn covering from ATS that came to the rescue of Scott Burdette. In cases like Scott's, cadaver skin is sometimes used as a temporary covering to protect the patient's recovering wounds. But cadaver skin is in limited supply, costly, and variable in quality, notes Michael Sabolinski, executive vice president of medical and regulatory affairs for Organogenesis, which makes a skin substitute called Apligraf. What's more, Sabolinski adds, cadaver skin is usually rejected by the patient's immune system within 20 days. But engineered skin isn't rejected, say the manufacturers.

Besides serving as burn coverings, engineered skin substitutes can help patients with diabetic foot ulcers. Today, most of these ulcers are treated with an approach that includes antibiotics, glucose control, special shoes, and frequent cleaning and bandaging. Despite this treatment, the ulcers are often slow to heal, and some don't heal at all. If an ulcer fails to heal, the patient's foot may have to be amputated. Of the more than 86 000 lower-extremity amputations in the United States each year, 85 percent are preceded by a diabetic foot ulcer, according to ATS. In a clinical trial, an ATS skin product designed for wound healing, Dermagraft, healed more chronic ulcers, and healed them faster, than conventional therapy alone, the firm reports.

The skin factory

With so much demand in view, firms developed the infrastructure to produce thousands of skin grafts every month. At Organogenesis' factory, though, it was a costly, by-hand process.

The company made Apligraf in petri dishes filled with a liquid nutrient that stimulates the skin's growth by mimicking its natural environment. The grafts start out as donated infant foreskin tissue taken from circumcisions. Such a source of cells is not just plentiful, it's incredibly potent. A sample the size of a postage stamp will multiply to such a degree that several football fields of skin graft can be crafted from it.

To start the process, the foreskin cells are separated into two types: dermal fibroblasts and epidermal cells. Tissue growth occurs over 20 days in several stages [see illustration, "Skin from The Factory"]. First, the lower, or dermal, layer of skin grows on a scaffold made of collagen (from cows), which is set in a shallow, round dish well-bathed in nutrient medium. Then a technician adds epidermal cells, which spread over the dermis to form the upper skin layer. Finally, the skin is lifted out of the culture bath so the top is exposed to air, which triggers the formation of a tough outer layer of dead cells. The process produces round skin patches measuring about 8 cm in diameter.

Using manual labor alone, Organogenesis could already produce about 50 000 skin grafts a year. But the firm planned to introduce industrial-scale automation. The first step would be to automate the addition and removal of nutrients, which is the most time-consuming operation. Without a periodic refresh, the growing skin will starve and poison itself on waste products. An electronically controlled system would make the process more precise and reproducible, while reducing costs and the likelihood of contamination, according to Leon Wilkins, vice president of technology development at Organogenesis. Those plans, like the company itself, are now on hold.