Artificial Skin: The Skin Trade
351 Term Paper
Key words: Epicel, Integra, Apligraf, and AlloDerm
TABLE OF CONTENTS
a. Artificial Skin been here since the 17th Century
a. Skin is vital for existence
b. Laboratory-grown skin
c. Artificial Skin
a. Artificial Skin, a science for the future
V. Annotated Bibliography
Each year more than 2 million burn injuries demand medical attention in the
United States. Ten thousand of these burned victims die every year from the burn-related
infections taking over their bodies. Tragically, many of these burned victims are young
children. The idea of artificial skin was noted many years ago. It has not been until
recently that the medical technique of artificial skin has been allowed to aid these victims.
This new and innovative procedure will help mitigate the above statistics. Already the
combination of advanced technology and complex medications can even help patients
with 90% of their body survive.
The concept of artificial skin dates back to at least the late-seventeeth century,
during which water lizard skin was applied in wound care. This particular practice has
since been abandoned in modern times. However, the need for an effective skin substitute
has remained urgent, especially in the face of burn victims and skin cancer patients. Not
surprisingly, over the past few centuries, a host of possibilities have emerged in the field
of skin replacement. In addition to employing animal skin (or xenograft), researchers
experimented with plastic sprays, sponges, and fresh skin from cadavers (allograft).
Cadaver skin proved to be the most successful in temporarily covering large wounds.
Nevertheless, problems with availability, disease transmission, immunological rejection,
and limited shelf life forced researchers to develop different alternatives.
This paper discuses four main products that have been developed to aid this field
of biotechnology. Epicel, Integra, Aligraf, and Alloderm are all different in their own way,
however they all have one thing in common; they are designed and manufactured to better
the lives of victims in need of replacement skin.
The human skin is vital for existence. The skin cools the body by secreting sweat
glands, maintains the perfect functional temperature for the body insulated by fat, protects
the internal organs from the outside environment, and fends off direct contact to disease
infested microbes. The body’s immune cells are resident in the skin as reserves to any
Figure 1- These are the vital components of skin.
There are many reasons that patients may need artificial skin ranging from severe
burns to car accidents. Any loss of skin can weaken the body’s protective system. Blood
loss that results from skin loss can cause the body’s blood pressure to drop so low that it
will not be able to transport blood to vital organs such as the brain, heart and kidneys.
Insufficient amounts of blood in the system equals loss of the flow of oxygen in the body
and therefore the halt of the body’s functions. The skin’s specifications play a vital role
for human existence and, if the artificial skin is not capable of those needs, it could be
fatal to the patient.
In such a case of a tragic burn, a burn surgeon must first come and remove the
damaged skin. The next step is to quickly cover the unprotected underlying tissue that is
now expose to the outside environment and bacteria. Two classes of biomaterials useful in
covering the wound are laboratory-grown skin cells and artificial skin. In some case the
two must be used together in order to secure the patient.
Funding for these two methods of covering and additional research on the body,
especially the human skin, come from the National Institute of General Medical Sciences
(NIGMS). Laboratory-grown skins cells is mostly the method of growing the
keratinocytes (skin’s epidermal layer), in a culture. This is not a simple technique because
each cell requires a unique set of conditions. Even when all precautions are made, some of
the cells will not grow. Dr. Howard Green of Harvard Medical School is a pioneer in
laboratory-grown cells. In his technique, Dr. Green takes the human keratinocytes onto a
layer of lab mouse-derived fibroblast (connective tissue) cells in a plastic culture dish.
This is similar to what naturally happens in nature. The technique works because it mimics
what happens in actual skin, whose lower layer called the dermis is composed
predominantly of fibroblasts. The principle function of fibroblasts is to produce proteins
called collagen and elastin that provide structure to skin. The product that results from Dr.
Green’s work is called EpicelTM. This is used to treat deep wounds that would require
grafting. This treatment can be helpful when treating both burns and accidents that may
remove the body’s skin.
EpicelTM is not artificial skin. EpicelTM must be taken from the patient in order to
initiate the culture growth. Artificial skin does not have to come from the patient. This is
an advantage to those tragedies that leave the patient with little or no remaining skin.
Artificial skin is very useful in covering the underlying tissue now exposed to the
environment and bacteria as well as promotes re-growth of natural skin instead of scar
tissue. This is an important distinction because scar tissue is less durable and flexible than
natural skin. The funding from the NIGMS established a reliable artificial skin system
called IntegraTM. IntegraTM is a successful result of the teamwork of two brilliant doctors
and their collaborating research teams. Dr. John Burke of the Burn Center at
Massachusetts General Hospital and Dr. Ioannas Yannas of MIT worked extensively
together in order to develop this helpful system.
At, first Dr. Burke used the skin of relatives to graft the new skin for the patients.
It was important to find a donor with similar genetic markers, so that the patient’s immune
system will not reject the implant. As additional precaution, Dr. Burke used potent
immunosuppressant drugs, that weakens the immune system temporily to allow the
implant to set without being attack by the patient’s natural defenses. A setback from this
procedure is that it was dangerous to the patient as well as the results were not permanent.
This is when Dr. Burke decided that artificial skin would prove to be helpful and answer
his systems problem. That is when he turns to work with engineer, Dr. Yannas. The merge
of biomedical engineering and clinical medicine proves to be successful in developing
Integra does not come from any living organism. Its primary function is to provide
a protective covering that allows the patient’s own skin cells to regenerate the lower
dermal layer that was removed or damaged. In actuality the dermal layer of the skin is too
complex to regenerate. The dermal layer contains hair follicles, sweat glands, and many
Dr. Burke and Dr. Yannas discovered a way to solve the problem of regenerating
the dermal layer. The remaining fibroblasts that lay deep within the skin can be instructed
through the lab to arrange themselves to resemble the dermis. This technique teaches the
existing fibroblasts and other supporting cells to act as healthy skin, not even scar tissue.
Integra consist of two main layers, just as real skin has two main layers (epidermal
and dermal). The bottom layer is made of bovine collagen and a sticky carbohydrate
molecule called glycosaminoglycan (GAG). Collagen is part of the structural basis in
mammals, similar to cellulose in plants. GAG chemically binds collagen taken from
animal’s tendons. It can be found in the animal’s cartilage. These two ingredients called
collagen- GAG are interwoven in order to mimic the fibrous patterns of the human dermis.
This bottom layer is designed to regenerate the real dermal layer. The second layer is a
thin sheet of silicone. This upper layer acts similar to the human epidermal layer on the
surface of the skin. The end product of Integra looks like a plastic wrap around the patient.
Figure 2- End product of Integra, looks like semi-transparent plastic wrap
This plastic casting is left wrapped around the patient for 2-5 weeks. This allots
time for the patient’s cells to begin to form a new dermis underneath the sheet of Integra.
The collagen-GAG material has poses with carefully controlled diameters that permit cells
to grow through the scaffold, which eventually is broken down and dissolved by enzymes.
Cells synthesize a new dermis at the same time that the scaffold is being broken down.
Epidermis then grows naturally over the new dermis unless the wound area is especially
large, in which case the surgeon does an autograft of epidermis-a much less problematic
procedure than grafting dermis, because epidermis is one-tenth as thick and is constantly
being shed and regrown. After the 2-5 weeks have passed, the Inegra layer is removed and
a thin layer of the patient’s epithelial cells is applied to the wound. Over time the skin
excluding the hair follicles begins to regenerate into a functional epidermal layer.
Apligraf is another product of artificial skin. Apligraf is used with standard
therapeutic compression for the treatment of noninfected partial- and full-thickness skin
ulcers due to venous insufficiency. Apligraf is only considered after conventional ulcer
therapy has failed and if the ulcer is present more than 1 month in duration. It is first tested
by analyzing Keratinocytes and fibroblasts derived from neonatal foreskin and expanded
in culture and then tested for infectious pathogens and immunogenicity. Like Integra,
Apligraf comes from bovine type I collagen used for the dermal matrix. Another similarity
is that they both are developed artificial skin construct that contains the important
elements of skin: extracellular matrix, dermal fibroblasts, and an epidermis containing a
protective stratum corneum.
Figure 3- Apligraf contains only the essential components of human skin covering.
A bilayered viable skin construct that contains both an epidernmal layer, formed
by human keratinocytes (with a well-differentiated stratum corneum), and a dermal layer
composed of human fibroblasts in a bovine type 1 collagen lattice. Apligraf contains the
matrix proteins and cytokines like found in human skin. However Apligraf does not
contain Langerhans' cells, melanocytes, macrophages, lymphocytes, white blood cells,
blood vessels, hair follicles or sweat glands. This can be seen in Figure 3 above.
On January 1999, this new product was put to a life or death test. Eight-week-old
Tori Cameron (picture on right) was born with a rare, painful and potentially deadly skin
disease called epidermolysis bullosa
that causes severe blistering with the
slightest touch. The disease causes
infections and raw spots, similar to
second-degree burns. Young Tori is
the first newborn that Apligraf has
been applied. 40% of her body was
covered with Apligraf. The surgery was so successful that even the doctors said that they
had a difficult time discerning the artificial skin to the new skin.
Artificial skin is a fairly new technique that is practiced in the medical world
today. Along with Dr. Burke and Dr. Yannas there are many doctors devoted to this new
form of medication. Another product funded by the National Institute of General Medical
Sciences is called AlloDerm. Its main agenda is to preserve as much of the natural three-
dimensional structure of the dermis as possible. AlloDerm is produced by removing from
cadaver skin all cell components that cause a burn patient's immune system to reject a raft
from any other person. A key feature of the process is preserving to the greatest extent
possible the "natural," three-dimensional structure of the dermis. Properly approximating
this scaffold, whether from real dermis (as in AlloDerm™) or artificial dermis (as in
Integra™), is crucial to the ability of the patient's remaining cells to regenerate themselves
into a new, functioning skin.
Name of Product Origin
Epicel Taking from patient-not artificial skin
Integra Collagen- GAG
Apligraf Bovine type I collagen
AlloDerm Cadaver skin
Figure 4- This table summarizes the products and their main components
The field of artificial skin is constantly expanding. With the direction of gifted
doctors and researchers and the advancements of biomedical technology, the art of skin
growth will be mastered. The damage caused by severe burns or a car accident will be
easily treated and patients can go on with their normal everyday lives.
National Institute of General Medical NIGMS
Dr. Cindy Klevickis,
I have addressed all that Karen Hutherson, revised on my artificial skin paper. She
thoroughly edited my paper for grammar as well as the overall flow of the paper. I
especially appreciated her input about starting new ideas with each new paragraph. That
writing critique will help me with my papers and reports to come. I have added all the
missing parts to my paper. It now has all the required components. I hope that by the end
of the paper that the reader comes away with half the appreciation and knowledge that I
have gained about artificial skin just from writing this term paper.
Current Surgical Diagnosis & Treatment, Lawrence W. Way, ed., Lange Medical Book, Appleton & Lange,
This is another basic procedure book on burns and skin replacement.
Nursing Care of the Patient with Burns, Florence Greenhouse Jacoby, ed., The C.V. Mosby Company, 1976.
This is an excellent handbook and guide to treatment for burns from the first contact all the way to
the hospital operating room.
Wound Care, Cathy Thomas Hess, RN, BSN, CETN, Springhouse Corporation, 1995
Handbook on burns and emergency care for burns.
Site informs about the UK acceptance of Integra
This site provides background information on the CE Mark Certification
This site hosts many sites that provided useful information on Integra and Integra
Internet site with useful and interesting background information about the origin of artificial
skin. Also site where the Integra picture was located.
Integra website devoted to the LifeSciences Holding Corp.
MIT student, Alice Waugh, discusses the uses of artificial skin in journal TECH Talk.
This is website that provided the case of Tori Cameron and the successful application of
This is another good journal site for a broad over view of artificial skin and its applications
in the medical world.
Another good site for the Cameron case and provided good pictures as well.
Expert, Richard Grace, gives his insight on the direction of artificial skin and the growing
science in his personal journal.
This is the main website for Apligraf information. Impressive figures and statistics.
Journal Scientific American on artificail skin.