The burgeoning field of tissue engineering promises to be one of the most significant biomedical areas of the new century. The hope is that, eventually, whole organs could be manufactured to replace those that are injured or diseased. The field's first contribution to health care took a big step toward fulfilling these promises by producing artificial version of the body's largest organ, skin.

Skin is a difficult organ to transplant because of its inherently strong immune defense system. Nevertheless, it has a relatively simple structure, making it a good testing ground for the talents of tissue engineers. Patients can have skin made to order that combines collagen as a binder with living human cells. This is placed onto a wound, usually a chronic ulcer or a burn, and its cells become activated and gradually integrate with those of the patient.

In 1997, the U.S. Food and Drug Administration approved a synthetic skin called TransCyte®, made by Advanced Tissue Sciences in California, for use as a temporary wound cover for burns. TransCyte consists of human dermal tissue, the lower layer of skin, combined with a synthetic epidermal layer, the upper layer of skin. After application to the burn wound, TransCyte provides a temporary covering to help protect the wound from fluid loss and reduce the risk of infection. TransCyte stays in place until a sufficient amount of the patient's own skin is available for grafting (in the case of third-degree burns), or until the patient's own skin heals (in the case of second-degree burns).

Another of the company's synthetic skin product, Dermagraft, is in clinical trials for the treatment of diabetic foot ulcers. Dermagraft is created by seeding fibroblasts from human skin cells onto a three-dimensional polymer scaffold that the body eventually adsorbs. The cells grow and divide within an enclosed bioreactor, which simulates the natural environment of the body, to produce collagen, structural proteins, and growth factors found in healthy tissue.

In 1998, the FDA approved Apligraf®, an artificial skin developed and manufactured by Organogenesis Inc., to treat venous leg ulcers, then in June 2000, gave the company approval to use the product for treating diabetic foot ulcers.

Like human skin, Apligraf consists of living skin cells and structural protein. A base layer combines collagen from cows and human skin cells, which produce additional matrix proteins. The upper epidermal layer is formed by prompting human epidermal cells, called keratinocytes, to multiply then differentiate, resembling the natural architecture of human skin.

Every year in the United States, 1,500 patients require extensive grafts due to third-degree burns. Nearly 40,000 are treated for second-degree burns. Up to 800,000 people suffer from diabetic foot ulcers, which lead to more than 80,000 amputations each year. Diabetic foot ulcers are conservatively estimated to cost the U.S. healthcare system over $1 billion per year.

Venous leg ulcers are another widely occurring chronic wound. Using artificial skin treatment, wounds heal faster than standard care alone and to provide average savings of $7,500 per patient for hard-to-heal venous ulcers. Other uses are being explored, such as reducing scarring after skin cancer surgery. In recent months, Apligraf has become more widely available to Medicare patients due to favorable reimbursement decisions at the national and regional levels.

There are several other tissue engineering products now in regulatory trials, and several more in preclinical development. One is artificial cartilage. Replacements to worn-out or damaged cartilage are also in great demand by the aging baby boomer population, and several catilage transplants are in development. The first replacement cartilage product approved in the United States was Genzyme's Carticel, which is made from chondrocytes taken from the damaged knee of the patient and grown on a degradable matrix. The Curis company is developing Chondrogel, which is an injectable mix of autologous chondrocytes and hydrogel polymer. It is currently in phase-three trials.

Advance Tissue Sciences got a boost when it received a three-year, $1.4 million grant from the National Institutes of Health to develop and produce cartilage for people with knee injuries. The grant allows ATS to enhance its patented bioreactor to grow cartilage under stresses such as compression and fluid flow. By mimicking the natural forces that affect cartilage in the body, company officials say the tissue-engineered cartilage could be similar to native cartilage. Focal articular defects---small, finite wounds in cartilage---affect more than 500,000 people per year.

If successful, artificial cartilage could prevent nearly 250,000 knee replacements performed each year in the United States.