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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.
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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.
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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.
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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
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| 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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Click on any photo for a larger view in a pop-up window.
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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