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In very severely burned patients who have little or no remaining intact skin, artificial skin is an extremely useful material not only to cover and thereby protect the wounded area, but to promote re-growth of a natural skin instead of scar tissue. Studies begun in the early 1970s and continuing into the 1980s led to clinical testing and commercial production of an artificial skin system called Integra Dermal Regeneration Template™ (Integra DRT). Every similar artificial skin product that has since been researched and developed hinges upon the conceptual framework that eventually yielded this artificial skin system.

Application of Integra
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The brainchild of a trauma surgeon and a mechanical engineer, Integra DRT is a prime example of an investment in collaborative research. In the early 1970s, surgeon Dr. John F. Burke, then director of the Burn Center at Massachusetts General Hospital and Shriners 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 very poor prognosis that severely burned patients faced. 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 burn patient be given powerful immunosuppressant drugs, to dampen the patient's immune system so that the graft would not be rejected. Unfortunately, although this method proved successful in treating extensively burned patients, crippling the immune system in this way posed many serious and difficult clinical problems. In addition, Dr. Burke used the patient's own unburned skin (often from the scalp, which is rarely burned) as a source of graft material.

One Week after Application
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However, since using these sorts of grafts (or even skin from cadavers) did not permanently solve the problem, Dr. Burke saw the need for some type of artificial means to replace lost 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, who had a penchant for engineering, recruited a clever mechanical engineer at neighboring MIT, Dr. Ioannas Yannas, to cooperate in this effort. The collaboration, marrying biomedical engineering with clinical medicine, proved fruitful. After initial testing in animals, the artificial skin that Drs. Burke and Yannas developed proceeded to rigorous scientific testing in humans, in a multi-center clinical trial.

Integra DRT contains no living components, and it is not itself actually designed to be a replacement skin.

Rather, it induces dermal regeneration and 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.

Actually, unlike analogous skin cells of certain amphibians and other types of animals, human dermis cannot regenerate.

Second-stage Integra Grafting
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In addition to fibroblasts and other cells, human dermis also contains hair follicles, sweat glands, and networks of blood vessels. As it contains so many diverse components arranged just so, the dermal layer is nearly impossible to replicate. What Drs. Burke and Yannas discovered, however, is that remaining fibroblasts deep within a badly burned wound can be "instructed" on how to arrange themselves into something resembling a real dermis. Basically, the trick is to coax those existing fibroblasts and other supporting cells into a pattern that resembles normal, healthy skin and not a scar. Proper patterning of the many components of skin is a vital feature permitting this tissue to carry out its multiple tasks for the body.

Integra DRT consists of two layers, just as living skin is structured. The bottom layer, designed to "regenerate" the dermal layer of skin, is composed of a matrix of interwoven bovine collagen (a fibrous cow protein) and a sticky carbohydrate (sugar) molecule called glycosaminoglycan that mimics the fibrous pattern of dermis. 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 DRT over the wounded area of the patient and leaves it there for two to four 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 DRT 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. Key features of this material's design are the number and size of the holes in the collagen/glycosaminoglycan matrix as well as the rate at which the matrix disintegrates. The precise balance of these two components allows real skin to take hold.



Integra DRT used on a patient with burn injury to the arm

   
1. Meshed Integra placement on fascially excised arm 2. Integra engraftment two weeks later 3. Thin epithelial autograft one week after silastic replacement 4. Four year follow-up

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Integra DRT was originally licensed, tested, and produced by Marion Laboratories of Kansas City, Missouri and is now being manufactured and sold by Integra LifeSciences Holdings Corporation, of Plainsboro, New Jersey.

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