Basic information about skin replacement, including new technologies that offer promising results.

The skin is the largest organ in the body, and this highly dynamic network of cells, nerves, and blood vessels serves the body in diverse ways. Clearly, the skin’s protective function is paramount, providing internal organs and tissues with a barrier from toxins, heat and cold, disease-carrying microbes, and other dangers in the environment. But skin also plays an important role in preserving fluid balance and regulating body temperature. Nerves within skin sense the presence of potentially harmful invaders, such as bees, and immune cells in the skin help the body fight disease.

For these reasons, the loss of skin due to burns or trauma can deal the body a severe blow, impairing or even eliminating the many vital functions this organ performs.

Burns

Each year in the United States, 1.25 million burn injuries require medical attention. Ten thousand people die every year of burn-related infections. The good news is that, in recent years, survival statistics for serious burns have improved dramatically. Twenty years ago, for instance, burns covering half the body were routinely fatal. Today, patients with burns encompassing 90 percent of their body surface can survive, albeit sometimes with permanent impairments.

Burn-induced skin loss allows bacteria and other microorganisms to access the warm, moist, nutrient-rich fluids that course through the body, while at the same time it provides a conduit for the rapid and dangerous loss of fluids. Hence, replenishing skin lost to severe burns is an urgent matter in the care of a burn patient. When a patient has lost 80–90 percent of the skin as a result of direct contact with scalding hot liquids, flames, chemicals, electrical current, or radiation, two immediate tasks come to the fore.

First, a burn surgeon must remove the burned skin, then the unprotected underlying tissue must be quickly covered.

Laboratory-Grown Skin Cells

In the mid-1980s, Dr. Howard Green of Harvard Medical School conceived a method for growing a type of human skin cells called keratinocytes outside of the body.

The product that eventually resulted from Dr. Green’s work, called Epicel, is used to treat deep wounds that require grafting (skin replacement), such as occurs with severe burns. However, since Epicel replaces the lost epidermal layer only, it works best in combination with something that restores the dermal layer of skin. Epicel is not an artificial skin, but rather a method in which new epidermis is “grown to order” in a laboratory from surgically harvested skin cells taken from an unburned area of the patient. Products like Epicel are termed “autologous” grafts, meaning that the source of the epidermal graft material is taken from skin of the same patient who receives it.

Artificial Skin

In severely burned patients who have little or no remaining skin, artificial skin is an extremely useful material not only to cover and protect the wounded area, but to promote re-growth of natural skin instead of scar tissue. In the early 1970s, Dr. John F. Burke, then director of the Burn Center at Massachusetts General Hospital and Shriner’s Burns Institute, came up with the idea that completely removing badly burned skin (as opposed to letting it slough off over time) might offer greater protection against wound infection and improve the prognosis of severely burned patients. Dr. Burke recognized that a necessary follow-up to the removal of burned skin would be immediate and permanent skin replacement. Once developed, his idea ultimately became standard practice for treating major burn injuries.

At first, Dr. Burke pioneered the use of skin from related donors (such as family members with similar genetic markers). But doing so required that the patient be given powerful drugs to dampen his or her immune system so that the graft would not be rejected. Unfortunately, crippling the immune system in this way posed many serious problems.

Dr. Burke saw the need for some type of artificial means to recover skin. Using a synthetic product would also offer an advantage in that such a material is free of viruses and bacteria, which can transmit disease. Dr. Burke recruited a mechanical engineer at neighboring MIT, Dr. Ioannas Yannas, to cooperate in this effort. The collaboration proved fruitful, and the artificial skin that Drs. Burke and Yannas developed came to be known as Integra.
 
Integra contains no living components, and it is not itself actually designed to be a replacement skin. Rather, it supplies a protective covering and a pliable scaffold onto which the patient’s own skin cells can “regenerate” the lower, dermal layer of skin that was destroyed by the burn.

Integra consists of two layers, just as living skin is structured. The bottom layer, designed to “regenerate” the dermal layer of real skin, is composed of a matrix of interwoven bovine collagen and a sticky sugar molecule called glycosaminoglycan. This matrix is then affixed to a temporary upper layer: a medical-grade, flexible silicon sheet that mimics the epidermal, or surface, layer of skin.

The product looks somewhat like translucent plastic wrap. After first removing tissue destroyed by the burn, a burn surgeon drapes Integra over the wounded area of the patient and leaves it there for 2­–4 weeks, during which time the patient’s own cells make their way into the matrix and create a new dermis. The top layer of Integra is then removed, and a very thin sheet of the patient’s own epithelial cells is applied. Over time, a normal epidermis (except for the absence of hair follicles) is reconstructed from these cells.

On the Horizon

Since burn and trauma victims endure injuries that affect many body systems besides skin, NIGMS sponsors research aimed at understanding the complex, multi-organ response to injury caused by trauma or burns. For example, research on smoke inhalation injury, which causes the majority of burn patient deaths, has led to changes in treatment practices in burn units. NIGMS-funded work by Dr. Daniel Traber of the University of Texas Medical Branch at Galveston and Dr. Robert Demling of the Burn Unit at Brigham and Women’s Hospital in Boston has shown that the right combination of aerosolized medications and hormones, delivered straight into the lungs, can significantly decrease airway damage due to smoke inhalation.

Proper nutrition may seem far from the minds of a critically injured burn patient and his or her doctor. But delivering the wrong mix of nutrients and minerals into the bloodstream can do more harm than good. NIGMS-funded research by Dr. David Herndon of the University of Texas Medical Branch at Galveston contributed to this conclusion by showing that making the intestinal tract “work” (by feeding the patient by mouth, instead of intravenously) keeps bacteria that normally live in the stomach from seeping into the bloodstream and causing infections that often lead to deadly septic shock.

Finally, NIGMS is funding other research on skin replacement, including a strategy to remove keratinocytes from non-burned epidermal skin, grow the keratinocytes into large sheets of cells in a laboratory, then place the sheets of cells on top of a collagen-based matrix that has been bathed in a nutritious mix of growth factors. When the material is grafted onto a patient, these factors prod the growth of new blood vessels. Dr. Steven Boyce of the University of Cincinnati and the Cincinnati Shriner’s Burns Hospital has succeeded in expanding a small number of skin cells into a transplantable sheet that can be layered on top of Integra. Dr. Boyce has assessed this method in a small number of patients, and has obtained promising preliminary results that the method offers a significant advantage over other currently available technologies.

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Adapted from: “NIGMS-Supported Basic Research on Skin Replacement Following Burn or Trauma Injury,” by Alison Davis. National Institute of General Medical Sciences, National Institutes of Health.