Friday, December 14, 2007

Skin Grafts: Past, Present, and Future

Skin grafting is currently an incredibly important procedure for the thousands of people who survive devastating trauma with extreme, life-threatening burns. The practice of taking samples of skin, either from the inflicted patient or from an allogeneic source, and attaching them to the damaged area produces beneficial results that set the patient on the road to recovery. Skin grafts allow people who would otherwise be functionally or aesthetically debilitated due to their injuries to regain the utility and appearance of their epidermis. Over the past 40 years, the traditional methods of skin grafting, which involve the use of either a live or cadaver donor to directly harvest the grafts, have cemented themselves as routine, safe, and effective. Over the past 20 years, though, the pace of innovation and experimentation in the realm of skin grafting has significantly quickened. New techniques, procedures, and assistive products being used in the medical process of grafting are paving the way for more successful skin transplants and faster, more consistent healing. Although these reports of exciting research and development are focused on restorative measures for patients who have survived painful accidents, the advancements made may also be put to use in more superficial situations. There always exists the inevitable potential for medical progress to be used for superfluous, ultimately unnecessary reasons, and the case of skin grafting is no different. Many of the innovations presented in these articles could easily be transformed into the next 'hot procedure' for the more affluent members of the community.

In this blog, we provided and analyzed a collection of articles that we felt highlighted the newest, most ingenious, and most controversial innovations emerging in the field of skin grafting. The articles, appearing in various news, magazine, and scientific journal publications, widely range in topic; the use of cells which display malignant behavior in transplants, the method of actually spraying on skin cells for grafting, and the manipulation of color and tone in grafts are just some of the issues and advancements discussed in the articles themselves and our blog post responses. The format of the blog lists the articles chronologically according to their publication date—in this way, it is possible to trace the media's attention to and descriptions of the medical advancements in the field of skin grafting. Our blog responses critically analyze these lay-press representations of the innovations and their ethical and social implications.

In skin graft surgery, a variety of new techniques are being developed. These techniques are used in the actual grafting procedure to enhance post-operative care or to use skin to make other organs. One technique used on patients with extensive burns that cover 50 to 60% of their bodies involves extracting skin, allowing the epidermal cells to grow, and then spraying it back on the patient. This is different from the usual skin grafting procedure in which they stretch skin over the damaged area. This is an important advancement because it allows to autologous grafts on a wider range of patients. Post-operative care is very important in skin graft surgery, because if the graft is not a good match, it can become infected or be rejected. Another interesting practice involves the use of leeches during post-op care to encourage the flow of blood. By eliminating the pooled blood under the skin, the leeches make the graft healthier and allow it to heal and integrate with ease. The leeches also help because they have a blood thinner in their saliva and they numb the body while they feast. Another fairly recent technique that researchers are observing is the use of Therapeutic Ultrasound. From rabbit testing, TUS shows that tissue that has received this treatment has a larger number of new blood vessels and a significant increase in proliferating skin cells. In another medical arena over the last few months, skin cells have been harvested to grow the tissue needed to make blood vessels. If the use of these engineered blood vessels proves effective, this will be a revolutionary breakthrough in heart surgery; vessels will be artificially grown and the traditional harvesting of the saphenous vein or mammary artery for bypass will be unnecessary.

While embryonic stem cells have long been seen as the most effective and reliable source for skin cells, due to the plethora of moral and ethical controversy surrounding the deliberately aborting embryos, scientists and researchers are on the lookout for different sources. The makers of Cytograft in Argentina have discovered that taking a small swatch of skin from the back of the patient’s hand or the inner wrist are great sources for skin cells; once enzymes have been added to extract the necessary fibroblast cells, extracellular matrix, and serve as the framework for tissues. In America. a new kind of artificial skin, ICX-SKN, is being created from a matrix made from the skin cells that make new tissues in the body. Even the foreskin of circumcised babies has been used as a source for stem cells because they produce keratin in large amounts and never stop dividing. What is great about these new sources is that from one little piece of skin, scientists can create long grafts and engineer many new cells, ensuring that there will never be a shortage of skin cells. Now that so many sources have been discovered, the outlook for burn victims is increasingly positive.

While the use of the aforementioned mentioned skin graft techniques and procedures could be considered controversial, on a more fundamental level, the use of skin grafts is not controversial in the least. No one would begrudge a burn victim a healthier, less painful life, nor would they deny a patient suffering from ulcers the skin transplant that would cure them of their condition. The problem, then – the one true cause of controversy – is the source of the cells used to create skin grafts. There is a very limited source of skin cells that are continually viable and practical in all situations. Autologous skin transplants cannot be used on severe burn victims who lack enough healthy skin to cover their burns. Allogeneic transplants are avoided if there is a threat of an immune response, and while Epicel has recently gained FDA approval for the first xenogeneic skin transplant, using animals as possible sources of skin exposes humans to viral and bacterial infections that thus far have been restricted to other species – not to mention that animals rights activists will most certainly protest killing animals for the sake of human medical advancement. In order to overcome this lack of potent skin cells, the medical industry turned to the use of stem cells.

It is scientific fact that human neonatal foreskin fibroblasts in collagen gel form dermal skin-like tissue in vitro and that embryonic stem cells are the only human cells that are totipotent, which is to say that they can form all cell types, and have the potential to cure or treat all diseases with a significant cellular component. Therefore, it would seem ideal to use these totipotent cells in treating burn victims and other patients who require skin grafts. What makes the use of stem cells controversial is the fact that many conservative and religious groups view the destruction of a blastocyst as the murder of a human being. Thankfully, the use of two different techniques has allowed researchers to side-step this controversy.

The first method involves the harvest of adult epidermal stem cells from the skin of the patient or donor which have the capability to grow tissues with differentiated layers. These cells are attached to surgical gauze and grafted onto the patient. This creates viable transplant cells from unipotent stem cells and does not require the destruction of a blastocyst. This method is only used the most extreme cases, however. The second, more recent and exciting discovery is the creation of pluripotent stem cells from differentiated skin cells. Though this method has yet to yield transplantable skin grafts available for testing in clinical trials, and though the process of cell differentiation is currently unknown, the ability to grow any cell type without the destruction of the embryo has opened up several new avenues that can and will lead to the improved health and quality of life of burn victims everywhere.

Yet while the discovery of induced Pluripotent Stem Cells (iPS) should be greatly applauded – and the Yamanaka group congratulated with a trip to Stockholm next year – it is important to remember that this discovery, this supposed victory for both conservatives and liberals alike, did come at the terrible cost: the suffering of thousands of burn victims who would have benefited from stem cell therapy had this research been federally funded. Currently, President Bush is being lavishly praised for his continued stance against embryonic stem cell research. Supporters claim that had the president allowed such research, scientists would have had no incentive to look for alternatives to “embryo killing.” An examination of the facts, however, shows that the president deserves no such credit. Not only did President Bush limit stem cell research to a handful of aging stem cell lines, but he also prevented scientists who dared to do such research from using federally funded laboratories or equipment, or even consulting with federally supported scientists; his efforts thereby thwarted the research effort for about four to five years. Want definitive proof that the current administration’s efforts have nothing to do with the most recent breakthrough? The Yamanaka group who pioneered this method conducted their research in Japan, where they were unhindered by American regulations.

Regardless of who should ultimately receive credit, the discovery of iPS has freed skin grafting procedures and techniques from any surrounding controversies. All that remains is to look ahead and hypothesize as to what discoveries lay ahead. What advancements in skin grafting can be expected in the near future? To begin with, scientists will always have need fpr cells that grow faster – both in culture and when grafted to the patient’s skin. Continual growth would allow patients to not only develop thicker, stronger skin, but would also be extremely helpful for children who sustain severe burns and require skin that can grow as their bodies do. We can also expect future scientific discoveries to overcome immune barriers that currently prevent the widespread use of allogeneic and transgenic tissues.

All of these methods, however, are largely reactive. The future, it seems, will bring not just advancements in our ability to respond to trauma, but also in a more proactive response to treatment. If parents will soon be able to select for cancer-resistant genes – or perhaps even genes for intelligence or good looks – then it certainly may become possible to select for genes that produce thicker, healthier skin: skin that is less prone to infection (or even acne), skin that is resistant to burns and frostbite, skin that heals more quickly. At some time, improving on existing technologies or ideas may not be feasible, efficient, or even possible. If medicine reaches that point, future scientific discoveries will concern themselves not with improving these procedures and assistive products, but with improving the human species itself. Whether that would destroy our humanity, whether it would take away our highly valued human ‘essence,’ remains to be seen.

Tuesday, November 20, 2007

Artificial Skin Breakthrough

Nupur Shridhar

First, a note concerning my previous blogs: I had previously recommended that scientists avoid using stem and fetal cells to avoid a moral debate and instead find some way to create those cells in a lab. Imagine my happiness when I discovered that scientists have only recently (and very recently, this article is published in the 20 November 2007 edition of SCIENCE magazine) discovered a way to turn skin cells into stem cells. For more details see here: http://sciencenow.sciencemag.org/cgi/content/full/2007/1120/1 or go get the article and read it.
Also here: http://www.cnn.com/2007/HEALTH/11/20/stem.cell.reax/index.html

In continuing with my theme of artificial cells that mimic the structure and function of natural cells, this article talks of the artificial skin cells created by British researchers in June of this year. This is the first successful trial involving laboratory-made living human skin that was fully and consistently integrated into the human body. This is a new development in artificial skins cells, since previously, skin substitutes in the past biodegraded too quickly in situ. The new skin, ICX-SKN, is created from a matrix produced by the same skin cells that create new tissue in the body. Thus, the artificial skin cells were designed with a template that was created by looking at the way the body naturally functions.

Current trials have shown that the new skin was able to close and heal a wound site in just 28 days. If artificial skins can become easily produced and prove to be just as effective as skin grafts, then doctors and surgeons would no longer have to worry about a dearth of viable skin cells for transplantation or grafting. Theoretically, there could be an endless supply of skin cells for every burn victim and plastic surgery patient - without risk of rejection (the cells wouldn't trigger an immune response) and a reduced risk of infection. So what's next? The article states that researchers now hope to create a whole range of cell-based implants that can fully regenerate lost tissue, not just help wound sites heal.

This clinical breakthrough has also inspired me to continuing working towards my goal of perhaps one day becoming a biomedical researcher or engineer. Perhaps "inspire" is too strong a word - too trite, too stereotypical. Rather, it had convinced me that investing in science pays off. Sometimes, as it was in this case, a researcher does not have to create a new mechanism or discover a new drug or procedure. Simply imitating the body's amazing ability to heal itself is enough.

The way in which these scientists approached creating an artificial skin cell (by looking at the matrix created when new cells are formed) reminds me of the article read earlier in class that outlined some of the cases where patients who had terminal cancer had miraculous recoveries. One line from the article that I remember rather distinctly stated that treatments from cancer need to do what the body did in those patients who recovered: it targeted the cancer cells with absolutely no side effects, and no current treatment, from surgery to chemotherapy, is as effective and efficient as the human body. In the case of patients who need skin grafts, then, who have suffered burns that are so severe that their bodies' natural mechanism of healing has been damaged, it makes sense to use artificial skin cells that would work the way their own cells would have had they not been damaged.

I am a student who often thinks about the moral consequences of any scientific discovery. Yet the use of artificial skin cells does not seem to offend anyone or cross any line. All burn victims deserve care, and if we can generate their cure in a test tube instead of surgically taking it from another part of their body, then we, as a community, should do so. Creating artificial skin cells was a result of working diligently, thinking creatively, and doing right. Hopefully, it will soon become common medical practice and affect thousands of people worldwide.

Epicel is FDA approved

PR Newswire
October 29th, 2007

The FDA has granted Genzyme Corporation marketing approval for its product Epicel, which stands for cultured epidermal autograph. The rights were granted under the Humanitarian Device Exemption (HDE) for use in life threatening wounds due to severe burns. With its approval Epicel became the first xenotransplantation-classified product to be approved in the U.S. It is considered xenotranslplantation it includes animal cells.

The skin is taken from the patient and then grown on a layer of mouse cells, which expedite the growing process. The skin is grown in lengths which can then be used as grafts. The process takes 16 days to complete and then takes 3 to 4 weeks to incorporate after being attached. Epicel is meant for patients who have suffered damage to more than 30 percent of the body since they no longer have enough healthy skin to cover their burns, though it can also be used with split-thickness autografts. Dr. Rajiv Sood, medical director at Indiana University School of Medicine said that Epicel “has been the most important advance in burn care for the coverage of large total body surface area burn wounds in this decade”.

The press release from PR Newswire released October 29th, 2007 was very thorough in portraying Epicel in its entirety. It mentioned the antibiotics with which it was cultured and that traces of these antibiotics may still be on the graft. It also pointed out that the cells were grown in a medium of cells that have bovine and murine origin.

It also highlighted the danger of the grafts being xenotransplantation-classified. Since the cells were grown in the same culture as mouse cells, there is always the chance of contamination, even though the cells have been tested for bacteria, fungi and viruses. The press release also points out that since the effect of xenotransplantation is not yet known the patients who receive the graft should not donate blood or blood parts, tissue, breast milk, egg, sperm, or other body parts to be used in humans.

Epicel's approval is a big step. Though xenotransplantation is strictly regulated, at the moment there is no technology better than the Epicel cells. The FDA has been very strict about xenotransplantation and the only reason Epicel was approved is because there is not a better option. The HDE makes it possible for new procedures and technologies to be able to be distributed, but Genzyme should work to get general approval. If Epicel can get approval for widespread use then it would be a good option for all burn victims, and may even take over for cadaver donation.

Though the press release emphasized that the inclusion of mouse cells was a risk and that the recipients should not donate any part of their body, it left out a major component of transmission, child birth. With the inclusion of another species in the growing of the grafts there is always the chance that they will transmit a virus or pathogen that is not yet known in humans. If the patient then gets the virus they need to contain it to themselves and so they should not reproduce, in addition to bodily donation.

Yet if Epicel can be used effectively and prove that the xenotransplantation has no negative effects than it can be a very great resource for skin grafts. The harvested skin is the size of a postal stamp and can then be grown to cover the entire body. It would allow for there to be enough grafts available for all patients who need them.

Also the animal rights controversy that usually surrounds xenotransplantation doesn't really affect Epicel. Animal activists though in their plea that all animals are equal, don't really seem to care about mice. If the human cells were grown on animal cells other than mice, then there might be an issue, but as it stands right now there isn't.

-SH

Monday, November 19, 2007

Blood Vessels Grown From Patient's Skin

Article: Blood Vessels Grown From Patient’s Skin
Author: Lawrence K. Altman
Found in: The New York Times
Published: October 9, 2007

Researchers at Cytograft Tissue Engineering of Novato, California have developed a six to nine month method of growing blood vessels – taken directly from a small section of the patient’s skin – in a laboratory with the intent of implanting them to restore blood flow around a patient’s damaged arteries and veins. This is the first time that blood vessels have been created solely from a patient’s own tissues and used to make skin grafts. This is such a huge accomplishment that the findings were published in the current issue of The New England Journal of Medicine.

Since the vessels are made from the patient’s own skin, there is no need for anti-rejection drugs, which are costly and require the patient to use them throughout his entire life to avoid long-term rejection. Furthermore, there is no risk of an inflammatory response because there are no synthetic materials or scaffolding in these vessels. Engineering these vessels is a huge feat since infection is the leading cause of graft failure (the second leading cause is shearing, where the pressure causes a graft to detach from the underlying tissue).

Doctors interested in pursuing this research project went to Argentina to conduct their studies because the medical costs are significantly lower than in America, and in Argentina, they didn’t have to deal with the strict regulations of the conservative Food and Drug Administration. Eight Argentinean patients, all of whom were receiving chronic kidney dialysis, were volunteers chosen for the study because their vessels were already worn out and because the dialysis shunts allowed for an easy way to monitor the functioning of the new vessels. On those brave eight patients, doctors performed the first human tests of the vessels. So far, none of these patients have suffered any major side effects, however, because the procedure is so new, the longest follow-up has only been for thirteen months. The long-term effects and possible
complications are not yet known, thus this procedure will not be in practiced as standard medicine for quite some time.

In the study in Argentina, surgeons cut an artery and a vein from the forearm and joined them in a link, also known as a shunt, which provided access for the repeated needle punctures required to connect the patient to a dialysis machine. These shunts can last a maximum of fifteen years, but when clots and infections develop inside the shunts that reduce or stop blood flow, new shunts must be created and installed immediately.

To obtain the skin necessary for the procedure, a fifteen-minute biopsy is all that is required. The patient is then put under local anesthesia while the surgeon removes a piece of skin, including a strip of a vein about an inch long from the back of the hand or the inner wrist. Technicians take that strip of skin and vein and use enzymes to extract fibroblast cells, the most common connective tissue found in humans and animals. These cells synthesize and maintain the extracellular matrix of tissues as well as provide the structural framework for many tissues, known as stroma. Additionally, fibroblasts play a critical roll in wound healing, which is incredibly important after a patient has undergone a skin graft procedure. In the actual graft, fibroblasts provide the mechanical backbone for the sheets that are later peeled and rolled into a tube. Technicians also extract endothelial cells from the inner lining of the vein. Endothelial cells line the interior surfaces of blood vessels, control the transit of white blood cells into and out of the bloodstream, and are involved in various processes such as angiogenesis (the formation of new blood vessels), atherosclerosis, and thrombosis (blood clotting). The fibroblast and endothelial cells are then grown by the millions as sheets in a laboratory. Under a microscope, this new vessel looks like a vein, but it has the strength of an artery, which is important because over time the body will be able to remodel the cells from a vein into a vessel with the elasticity of an artery.

A vascular surgeon in Buenos Aires, Dr. Sergio Garrido, implanted the Cytograft vessels in ether the forearm or the upper arm of the patient while he was under general anesthesia in surgery that took a little over an hour (the intravenous fluid line was inserted in another area from the malfunctioning shunt). The Cytograft vessel, only five and a half to eleven and three-quarters of an inch long, feels a little more delicate than a vein.

Cytograft reported that the vessels do have great potential for patients with damaged blood vessels due to diabetes, arteriosclerosis, and birth defects. Dr. Toshiharu Shinoka, director of pediatric cardiovascular surgery at Yale, plans to conduct studies with the new vessel because of its enormous potential in the vascular surgical field. In Japan, where Dr. Shinoka has previously practiced, the vessels were grown from cells on a scaffold that degraded and were absorbed in the body. He was also particularly enthusiastic about the new types of cells because they may prove to be beneficial for infants and children with congenital heart defects; the vessels will be able to grow with the child – since they have the elasticity of an artery – eliminating the problem of repeating skin graft procedures as the child grows. Dr. Shinoko and Cytograft have agreed to start these studies within the next two years.

Vessels in the arm would be much easier to repair in an emergency than vessels implanted deeper in the body. Researchers hope that these new vessels will allow them to save the toes and lower legs of people with poor blood circulation due to arteries damaged by diabetes or arteriosclerosis, as well as use these vessels to treat patients who need coronary bypass surgery.

Since the vessels are grown in a laboratory, there are limits to the length the vessel, meaning that multiple short segments of the vein have to be sewn together in order to create longer vessels. Researchers plan to make a two-foot long graft from four shorter ones for lower limb grafts. To test the lower limb grafts, Cytograft is currently searching for willing patients in Poland and Slovakia. Cytograft realizes that in order to make these procedures more widely-used they need to experiment on humans in the United States, and has applied to the Food and Drug Administration for approval to conduct studies of the vessels in the United States provided that at least ten patients in Poland and Slovakia are healthy six months after treatment.

Because these procedures are so new and experimental, the cost of treating one patient is an astonishing $15,000-$25,000. However, these prices are expected to drop if the procedures become more common, and hopefully Medicare and private insurance companies will agree to cover the procedure!

Therapeutic Ultrasound and the Integration of Skin Grafts

Title: Can Therapeutic Ultrasound Influence the Integration of Skin Grafts
Author: Adriana da Costa Goncalves
Source: Ultrasound in Medicine and Biology Sep2007, Vol. 33 Issue 9 p1406-1412

Autogenous skin grafting is the most common skin graft procedure used. It can be implemented in a wide variety of circumstances from burns to reconstruction. The skin grafts usually heal on their own, except for in cases when tissue necrosis and eventual rejection of the entire graft occurs. In this case the area must be grafted again or another plan of action must be attempted. Since therapeutic ultrasound has been shown to effectively heal and regenerate skin, bone, muscle, tendon, and peripheral nerve tissue scientists are trying to explore if it can be used in accelerating skin graft integration.

The use of ultrasound in skin graft integration was done in a trial consisting of twenty female New Zealand rabbits. The rabbits received a skin graft in the dorsal region. The graft was covered over with a tie-over Brown type dressing for three days which was then removed to allow therapeutic ultrasound. In some cases the therapeutic ultrasound was done over the entire graft. In others the graft was divided into two parts, one that received the ultrasound (group 1) and one that only received the manual massage of the ultrasound head but not the actual ultrasound (group 2). After eleven days the animals were killed and the skin grafts were removed for study.

Results showed that there was no significant difference between the epidermal and dermal area between group 1 and 2 after eleven days. However it was observed that there was a significant increase in proliferating cells in group 1 at 12.18% compared to the 7.34% of group 2. It also showed that there was a significant amount of new blood vessels in the reticular layer of the dermis in group 1 compared to that of group 2. It was also observed that after 35 days there was no visible difference between group 1 and group 2.

The biological mechanism of ultrasound in the integration of skin grafts is still not entirely clear. However, the increase in proliferating cells and new blood vessels points to better integration. Yet, like in all animal testing the difference in rabbit and human skin must be taken into account. The results in the rabbit trials do suggest that human trials should take place.

If ultrasound proves to be effective in humans it could be very important to skin graft surgery. It could be used in graft rejection, since we still don’t really know why autologous grafts are rejected in the first place. It could solve the problem of having to regraft or not being able to graft on a particular person. Also, if it can help in integration, it could speed up recovery time, allowing patients to get out of the hospital and back to normal life faster, and ultimately cutting down on costs.

Sunday, November 18, 2007

Discovery on Manipulating Skin Tone

Title: Discovery On Manipulating Skin Tone
Date of Publication: August 26, 2007
Found in: Medical Research News

Scientists from the University of Cincinnati and Tokyo Medical University have been searching for ways to make human skin look healthier and younger by manipulating skin tone and color. While your mind may jump right to Michael Jackson’s horrendously bleached skin, the researchers are not looking for ways to improve skin bleach. They are looking to bioengineered skin grafts as a way to even out the colors and tones of skin that is either discolored or has patches of discoloration.

Part of the function of these bioengineered skin grafts is to help cosmetic companies develop new products so that people can achieve the perfect sunless tan. These skin grafts are not meant for people who wish to completely change the color of their skin, although this is a concern that must be addressed sooner than later. If this is not addressed, it is possible that people with light-colored skin who wish to be darker and people with dark-colored skin who wish to be lighter will subject themselves to whole body skin grafts to achieve a complete change in skin color. This would exponentially increase racial tensions nationwide, and possibly worldwide. However, once this kind of scientific advancement is made, it is quite a challenge to keep it out of the hands of the wrong people. This dilemma is similar to the debate about screening embryos for genetic predispositions to develop certain inherited diseases. While that is generally seen as positive, some people are against it because they believe that screening embryos will lead to the age of designer babies, which is seen by many as unethical. The line is just as fine for this research study: why is it socially acceptable to have skin darkened so that it is tanner, but not socially acceptable to have skin lightened? It seems as if making your skin darker is not perceived as wanting to change your racial identity, while making your skin lighter is.

The research study was published in the September issue of the Federation of American Societies for Experimental Biology journal (FASEB), and explained how, for the first time, scientists were able to manipulate skin color and tone by using cells that were previously thought to play no significant role in skin tone and color.

Researchers describe how the cells responsible for pigmentation, melanocytes, can be controlled by keratinocytes, the most commonly occurring skin cells. Keratinocytes make up 90% of epidermal cells (the cells on the outermost layer of the skin) and do not produce any pigment of their own. Working with bioengineered skin that is usually used for skin grafts to help burn victims recover posed a couple of difficulties for the researchers because they had to balance various mixtures of keratinocytes from people with vastly different types of skin colors and tones. The keratinocytes were found to produce chemical signals that tell the melanocytes to produce more or less pigment, called melanin, as well as how to distribute the pigment that they produced. Distribution is really important because it insures that the skin has even tones and colors and that there are not any patches of skin that are radically different colors from the rest of the skin on a person.

It has been known for a while that the more melanin produced, the darker the skin tone is, and conversely, the less melanin produced, the lighter the skin tone is. The researchers found that using keratinocytes from light-skinned people had a lightening effect on the bioengineered skin graft material, while keratinocytes from dark-skinned people had a darkening effect. This is incredibly important because it is the first conclusive piece of research that shows a solid link between keratinocytes and melanocytes. Additionally, keratinocytes are much easier to manipulate than melanocytes are.

Dr. Gerald Weissmann, Editor-in-Chief of the FASEB journal reported that the skin grafts were engineered so that they closely resemble the natural tone and color of the recipient, which was hypothesized to reduce the visibility of scarring. He also noted that this study is the beginning to unleashing the understanding of how and why different skin tones have evolved during the millions of years that humans have been in existence.

While it may seem that this study is only significant in the cosmetic world of medicine, this is not completely the case. The study’s senior researcher, Dr. Raymond Boissy, said that this study could also help to improve the quality of life for people suffering from pigment diseases such as melasma, vitiligo, and age spotting by making their skin look healthier. Melasma is a tan or dark facial discoloration most commonly seen in pregnant women and women on hormone replacement therapy. Vitiligo is a chronic skin condition that causes loss of pigment, resulting in irregular patches of pale skin scattered throughout the patient’s body. Perhaps if vitiligo and melasma patients had skin grafts enhanced with fully functional keratinocytes and melanocytes, the production and distribution of melanin could be altered so that the light patches of skin would gradually become darker, the dark patches of skin would gradually become lighter, thus patients would have a more even skin tone and an improved quality of life.

Saturday, November 17, 2007

Genetically Altered Cells May Help Artificial Skin Fight Infection

Title: Genetically Altered Cells May Help Artificial Skin Fight Infection
Author: Amanda Harper
Date of Publication: January 9, 2007
Published in: Journal of Burn Care and Research
Study funded by: Shriners Hospitals for Children

Dorothy Supp, PhD and her burn research team in Cincinnati have created genetically modified skin cells that when added to cultured skin substitutes may help fight off potentially lethal infections in patients with severe burns. They found that skin cells genetically altered to make higher levels of the tiny protein human beta defensin 4 (HBD4), which naturally exist in the body as part of its defense system, were able to kill more bacteria than normal skin cells. This is important because infections are a serious risk for patients who have recently received skin grafts.

The cells are taken from the patients’ own skin, cultured in a laboratory, then are expanded and combined with a spongy layer of collagen to make the actual skin grafts that can be reattached to the wound. It is good that the cells are taken from the patients’ own skin because the patients won’t have to deal with seeing someone else’s skin on their body, which while medically effective has proven to be somewhat psychologically damaging. These psychological effects were seen in one of our lectures where hand amputatee and had another man’s hand sewn on to his residual limb. While surgeons spent many painstaking hours attaching each blood vessel and nerve ending from the new hand to this man’s arm and the hand was functioning beautifully, the man could not deal with the psychological trauma of seeing another man’s hand instead of his own, and actually opted to get the hand removed and chose to have a prosthetic attached instead. However, what if the patient is so badly burned that there isn’t enough healthy skin from which to take cells to culture? Should the necessary skin cells come from a cadaver or an animal?

Supp has been conducting her study for three years and has learned how to successfully isolate the HBD4 gene from donated tissue samples and transfer it into surface skin cells, called keratinocytes, to give them enhanced infection-fighting abilities. These cells are then infected with pseudomonas aeruginosa, a type of bacteria most commonly found in hospitals, and allowed to incubate. When analyzed, Supp discovered that the genetically altered cells containing HBD4 were more resistant to microbial infections that the unaltered cells. These cells, if effective, could become an alternative method for burn wound care as well as for infection control in general.

If they are used in cultured skin substitutes, they may also decrease the patients’ risk for infection, improve skin graft survival and hopefully reduce the patients’ need for antibiotic treatment. Currently, physicians have to continually wrap the skin graft surgical wound in dressings coated in antimicrobial drugs to fight off infection. This is a time consuming process that does not necessarily rule out infection since antibiotics have to be given to the patient topically and orally, increasing the risk of the emergence of drug-resistant strains of bacteria.

The goal is to add these genetically modified cells to bioengineered skin substitutes in the hopes that they will provide an essential boost to the body’s natural defense system during the initial grafting period, when the skin is most susceptible to infection. However, cultured skin substitutes do have an increased susceptibility to infection since they are not yet connected to the body’s circulatory system at the time of grafting, and are therefore not able to circulate antibiotic drugs or antibodies from the body’s immune system to fight off infection.

Monday, November 12, 2007

Cadaver Skin Fills the Gap in Burn Cases


Title: Cadaver Skin Fills the Gap in Burn Cases
Author: Amanda Schaffer
Source: The New York Times
Publication: May 2, 2006

Although much new and innovative progress is being made toward the creation of artificial skin products for grafting, the treatment for burn patients chugs along, relying on older, more traditional methods. In the May 2006 New York Times article by Amanda Schaffer, “Cadaver Skin Fills the Gap in Burn Cases,” the reality of skin grafting and the most common source of skin for grafting—cadavers—is described and evaluated.

Cadaver skin, the most favorable option for grafting (aside from autologous grafts) over the past 40 years, has thoroughly cemented itself as a significant player in the realm of skin grafting. The skin is harvested from donors very soon after death; however, the process of searching for and locating viable donors can be difficult and unfruitful. Cadavers are only eligible after extensive testing for risk factors that may harm the patient, and even if the skin is deemed perfect for skin grafting, the family of the deceased must consent to the procedure.

The article clearly outlines the process involved in preserving cadaver skin. Any given cadaver can yield approximately four square feet of skin, and once removed, the skin is sliced into strips and stored in freezing temperatures. When needed for a graft, the skin is removed, put through a meshing machine to facilitate stretching of the skin, and subsequently attached to the affected burn area.

Cadaver skin has clear advantages for use in skin grafting. Using human skin instead of the new and exciting artificial skin products in development can lessen the chance for infection and quicken the healing process. Since it is a real human organ, graft patients may not feel as much of a difference between their unharmed and the transplanted skin. Logistically, cadaver skin is beneficial because it can be effectively stored for up to five years.

Although the article was thorough when describing the process of cadaver skin use and introducing several of the new research endeavors to create artificial skins such as Integra and Epicel, the path to becoming a skin donor and the function of skin banks were not heavily discussed. Schaffer briefly mentions that patients undergoing gastric bypass surgery who would like to donate excess skin cannot do so due to the shortcomings of current skin harvesting procedures—but doesn’t follow up to explain the techniques or why they are inadequate.

Becoming a skin donor may seem very straightforward — in many states, preference regarding organ donation can be listed right on the driver’s license. However, as previously mentioned, the family of the deceased must agree to allow skin to be removed after death, and when faced with the decision, many relatives refuse the procedure. “Skin donor program will help treat burn victims,” appearing in the Atlanta Business Chronicle, articulated the reality that many families are uncomfortable with this idea of skin donation— after all, how many people would agree to let their loved ones be ‘skinned’ before the funeral service? The thing that most families do not realize, however, is that grafts are mainly harvested from inconspicuous areas, such as the thighs and buttocks. These grafts can be extremely beneficial for burn victims whose bodies have been destroyed in tragic fire accidents. [@http://www.bizjournals.com/atlanta/stories/2000/10/30/focus6.html].

Should the decision to be a donor be less optional? In the USA, the percentage of listed donors who do not actually end up giving their organs, especially their skin, is rather high. Is there another way to encourage families to agree to the harvesting of their loved ones’ most prominent organ? If a donation is made, it is generally accepted that the costs required to remove the cadaver’s skin is absorbed by the tissue bank— but should an additional payment be made to families who assent? A financial incentive would probably increase the number of donations made, but admittedly, it sounds strange to pay people to give up pieces of their dead family members.

The endeavor to improve the effectiveness of cadaver skin grafting should be addressed with at least as much importance as the ventures to innovate artificial skins and new techniques for grafting procedures. Why? The enhancement of a pre-existing, proven-to-work method seems a wise path to pursue—after all, if cadaver skin grafting became easier and more accessible, maybe the development of synthetic grafts would not be as pressing of a matter. Perhaps the focus and efforts in the field should be centered on the advancement of current procedures rather than the creation of new ones. Unfortunately though, the funding for research and development is most often awarded to the companies pursuing the most exciting and ingenious new products and techniques. This reality may signal a need for reevaluation, in some situations, of the priorities that biotechnology strives to achieve. In this case especially, shifting the focus and resources to more basic forms of education and training may significantly benefit the given medical arena.

-JG

Spray-On Skin

Nupur Shridhar
11 November 2007

For the past eighteen years, I have been lucky enough to have been able to take my skin for granted. My current knowledge of skin, and by extension, skin grafting - both its purpose and its procedure - has been based on the fact that, with the exception of a few mildly-troubling, acne-ridden years in middle school, my skin has not let me down: it has served well as my first line of defense against bacteria and viruses, produced sweat at an alarmingly an efficient rate both during tennis matches and college interviews, and, most entertainly, has allowed for plenty of "What can Brown do for you jokes?".

In short, because I haven't had to concern myself much with what happens when skin stops functioning as it ought to, either as a result of the natural wear and tear that results from old age or from a traumatic experience, I have a great deal to learn through the course of this academic journey.

Skin grafts are most often used on burn victims. To prevent infection and restore natural function and appearence, pieces of skin from parts of the body that aren't burned are removed, stretched to almost six times their size, and surgically grafted - transplanted - over the burned portions. Risks for skin graft surgery include bleeding, infection, and rejection of the graft which leads to loss of the grafted skin. Unfortunately, those individuals who could benefit the most from skin grafting - those that have suffered the most severe burns over a greater percentage of their bodies - are also the ones that are severely limited by their ability to produce viable skin grafts. The reason for this, as Dr. Baljit Dheansa, explains to National Geographic is that patients who have burns that extend over 50 to 60 percent of the body "don't have enough of their own skin to cover them." Fortunately, there's hope: not only will the new prodecure reduce scarring, speed up healing, and allow patients to more quickly return to a normal lifestyle, it can also, in a relatively short time - four weeks - yield enough skin cells to cover the entire surface area of the body. This is done by taking a healthy piece of epidermis the size of a postage stamp and growing it in a laboratory to produce enough cells to spray over all damaged areas.

As a potential biomedical engineering concentrator, this article inspired me to continue learning more about such procedures for two main reasons. First, the advances in skin grafting procedures reported in this article reflect the ability of biotechnology to respond to the problems presented by the limitations in previous medical practicies. Even solely in terms of cost, one single spray treatment costs $9000, substantially less than the $3680 per day for the approximately two weeks that a burn victim remains in the hospital. As Atul Gawande can attest, there is always some way to make medicine better, and, someday, instead of reading about other scientists' discoveries, I'd like to be one of the researchers making those improvements. Second, I am a firm believer in the ability, and responsibilty, of biotechnology to not only improve the medical condition of a sick patient but also their quality of life. After all, at some point, a life filled with pain, physical or mental, is arguably no longer worth living, and for those burn victims for whom spray-on skin cells would provide a more attractive lifestyle - both literally and figuratively.

Biotechnology, however, must no longer focus exclusively on the healthy. While lifestyle medications like Viagra can improve the quality of life of many a man, every dollar invested in a "better" erectile dysfunction drug is one dollar less spent on a cure for a fatal medical condtion, say, for example, a newer, more effective HIV drug. There is, after all, something fundamentally wrong about a medical system that can guarantee an AIDS patient an erection but not an increase in life expectancy. Given this tendency to invest in lifestyle drugs, as well as the American tendency to commercialize any new procedure, I am worried that it will not be too long before a cosmetic procedure is derived from this medical one. To me, any procedure that would involved using spray-on skin cells to create younger-looking skin on healthy individuals would be a gross waste of medical time and money. As long as there individuals who die from diseases for which no cure has yet been found, or worse yet, individuals who die from preventable disease as a result of a lack of proper medical care and attention, there is no money to waste on development of cosmetic procedures.

Another possible consequence involves skin graft donation. Viable skin cells could certainly be taken from a donor - even an animal donor - instead of the patient. What happens, then, if this process is commercialized? Perhaps, younger, more attractive individuals like myself would have an incentive to sell their skin cells to others for a tidy sum of money. At last, a way to pay for this Brown education. On a more serious note, David Cutler, professor of economics at Harvard University and author of the book Your Money or Your Life: Strong Medicine for America's Healthcare System, would most likely agree with me when I say that creating a pecuniary incentive to donate skin cells would be unfair to poor Americans who can't afford food and clothing, never mind living life with half their skin and one kidney. In short, I am concerned that the public will once again look for a way to derive a better lifestyle for the healthy instead of focusing on the fact that for the sick, life must first go on before it can be improved.

In the end, however, I am most interested in learning how effective spray-on skin cell treatment actually is. At the time that this article was published in September of 2005, thousands of people had been treated with spray-on skin cells. How many of them actually had better results than those provided with traditional skin graft treatments? Were there instances where the damage was too severe for sprayed-on cells to work? Were there any side-effects? This is another characteristic of biotechnology inherent in all discoveries: there will always be gaps in knowledge that are a result of a lack of research. It is not at all a result of a lack of diligence, ingenuity, or intention to do right, and it is possible to assume that with time and more studies, these gaps in knowledge will be filled. In the mean time, spray-on skin cells seem to be a new and effective method of treating burn victims and one that promises much hope and improvement in quality of life.

In short, regardless of our role in the medical system, whether we are a doctor, a patient, a student, a professor, an overworked and unappreicated TA, or a blogger, we must all applaud the efforts made to develop this new technology and support and encourage, perhaps even participate in, efforts to create even better techniques.

Fetal Skin Cells

Scientists have discusses the theoretical potential of using human fetal cells to cure diseases and wounds for years. Only recently, however, did one group of Swiss scientists prove that fetal skin cells can be used to develop a type of "biological bandage" for severe burn victims. Before discussing the moral consequences of this new procedure, it is important to highlight its merits.

First, the procedure greatly speeds and improves the healing process. Eight children with severe second and third degree burns were treated; doctors at the University Hospital of Lausanne, Switzerland, treated these children with panels of artificial fetal skin, all grown from a postage-stamp-size sample of skin taken three years ago from an aborted fetus. Though these panels dissolved and had to be replaced every few days, they did not simply cover the burn with a layer of healthy cells; they actually seemed to "confer restorative power to the damaged tissue underneath, allow it to heal itself." The fetal cells actually stimulate healing.

Secondly, fetuses promise an endless source of skin cells for burn victims. As Dr. Holdfeld points out, while it is true that cells originate from terminated fetuses, one biopsy is enough to treat thousands of patients for years. Furthermore, the results are simply much better than traditional skin grafting, where skin is borrowed from another part of the body and grafted over the burns. Grafted skin, however, regenerates poorly, and is often painful and disfiguring, especially in children, since these grafts do not expand as the children's bodies grow, which means that they would require repeated, painful surgeries as they matured. In contrast, the children treated with the fetal skin were able to heal their wounds with skin that appeared more or less normal, with normal pigment and mobility. Since the fetal skin layers were simply placed on the wounds, the children required no surgery. Certainly, using fetal skin cells seems a completely promising and revolutionary practice.

When, then, can Americans look forward to such efficient and revolutionary burn treatment? Unfortunately, not any time soon. The laws in the United Stated restricting the use of stem and fetal cells will prevent any quick assimilation of these new medical practices, and the current administration seems keen on keeping it that way. Yet I believe that regardless of political stance, the use of fetal cells is justified in this instance.

The cells come from aborted fetuses. Therefore, as long as abortions are still legal in the United States, there will, however unfortunately, be a supply of fetal cells that can be used to help and heal others. Despite what critics say, using cells from a fetus would not increase the number of abortions or cause more women to abort their babies. Simply put, this new procedure will be making use of something that society currently has no use for - indeed, often condemns.

On a deeper level, though, if one were to examine exactly what doctors and medicine owe, one realizes that it is better to treat the sick than the dead. As Atul Gawande would not, doctors have an obligation to attempt to provide their patients with the best possible treatment. What if using fetal cells for their burns was the best possible treatment? Clearly, Swiss citizens will soon have access to this form of treatment. Why deny it, then, to a similar patient on this side of the Atlantic? The best thing for doctors to do would be to continually attempt to give their patients the best treatment possible, whether that would be to counsel against unsafe sex or write a prescription for birth control or conduct safe abortions only when necessary and donate the fetus to a research facility that would use the cells to save other lives. In the end, the fetus is already dead. The burn victims, however, are very much alive, and the pain that they feel pain is very real and deserves immediate treatment.

Something I realized through the course of my academic journey, however, is that many of these new treatments for skin grafts - and most other diseases - cause us to question what our morals ought to be. Is a face transplant an entirely superfluous surgery? Or does it give another human being a second chance at a normal life? Are cosmetic surgeries simply one application of new medicinal discoveries? Or is America's Consumerism driving this need to develop more procedures that "improve" instead of heal? In the end, I would like to see scientific discoveries that completely avoid these moral issues. If science can find miracle uses for stem cells and aborted fetuses, it can also attempt to synthesize these same materials in a lab without dealing with the issue of human life and when it begins. Though I am a very liberal aspiring scientists, I understand that not everyone else is, and that medicine has an obligation to help everyone, even if that means coming up with a different, and hopefully better, procedure that does not conflict with their personal beliefs. In short, if we can generate cells in vitro that the do the same thing as stem or fetal cells, then we have all the merits of this research without the [im]moral consequences.

To anyone who does oppose the use of these cells, however, I would like to pose the following question:
Suppose you are in a building when the fire alarm goes off. You smell smoke and want to get out of the building as soon as possible. You are not, however, alone in this room; in front of you are a crying and frightened child and a freezer filled with 1000 stem cells, each of which is viable and could produce a baby. You only have time to save one: the child or the freezer. Who do you save?

Leeches in Post Skin Graft Care

Title: Beyond Bloodletting: FDA Gives Leeches a Medical Makeover
Author: Carol Rados
Source: FDA Consumer Sep2004, Vol. 38 Issue 5 p9

When one hears about leeches in the terms of medicinal use, he conjures up the image of Victorian England and the absurd practice of bloodletting. Yes leeches have been used in ailments from fevers to gangrene and their use did peak around the mid 1800s, but these events have just given leeches a bad rap. The use of leeches can no longer be considered barbaric as they are currently being used again as a medicinal tool in skin grafts and blood flow. Their primary purpose in these cases is to drain pooled blood which can threaten tissue survival.

The use of leeches is not only done now but it has been given credibility when the FDA approved the use of leeches in June of 2004 as a medical device. A medical device is categorized as anything “intended to diagnose, cure, treat, prevent, or mitigate a disease or condition, or to affect a function or structure of the body, that does not achieve its primary effect through a chemical action and is not metabolized.”

Companies that have started supplying leeches for medicinal purposes after 1976 have to be FDA approved. Use of leeches though allowed has not exactly become common practice, Rod J. Rohrich president of the American Society of Plastic Surgeons says he only uses leeches when they are absolutely necessary. Though they are again considered to be medicinal, public reaction and adversity to leeches causes the use of them to be far less frequent. Not many of us would assent to having leeches attached to our face and hands.

Leeches are used post reconstructive or skin graft surgery when the vessels in the injured site can not clear the blood. The physicians are required to find a way to move the blood so it won’t cause damage to the surrounding tissue. Leeches aren’t used to replace the body’s vessels but to give them a jump start since the suction and function usually allows the vessels to start to work on their own. This is important in the case of skin grafting when the vessels in the new skin must be integrated into the body’s vascular system and allow healthy assimilation and function of the new tissue. The leeches function primarily by removing blood but that’s not what makes them so useful. The hirudin that their saliva contains is an anti-clotting agent that allows the blood to move more smoothly. Also they release an anesthetic during feasting which minimizes pain in the surrounding area.

Two to three leeches are usually applied at a time and drink for approximately forty minutes until they fall off and are replaced by a new team. The leeches are extremely cost effective at seven to ten dollars per leech. You may even be asking why they are that expensive, and it is because the leeches used medicinally are not the ones you will find in a pond or a lake. These leeches are raised in controlled and sanitary environments, most often in a lab. This is done with the goal of protecting patients from infection from antigens that may be existent in leeches found in the environment. As in all cases of hospital care, sterility is a major concern. Also, once leeches fall off they are treated as infectious waste material and must be handled accordingly.

The use of leeches in post skin graft care is most interesting to me, because it poses the question of what cures we can find from old cures or organisms existent in the environment. As medicine tends to progress it usually thinks itself as too good to use thousands of year old methods, however in the case of leeches it proved to turn out well. Medicine instead of looking forward for synthetic materials and compounds that don’t exist yet, should take a step back and look at the world around them. The majority of medicines used today come straight from the earth, like penicillin.

Sunday, November 11, 2007

Immortal Skin


Title: Immortal Skin
Author: Rebecca Skloot
Source: Popular Science Magazine
Publication: December, 2001

If you were caught in a fire and sustained traumatic, 3rd degree burns, what would you risk to regain and re-grow your healthy skin? If a treatment for burns that involved grafts formulated by cells which exhibited characteristics of malignant cells, would you consider getting the graft?

The article, “Immortal Skin” by Rebecca Skloot, which appeared in the December 2001 issue of Popular Science magazine, reports on a new type of skin cells that never stop dividing. The ‘immortal cells’ discussed in the article were the discovery of Lynn Allen-Hoffmann, a pathology professor at the University of Wisconsin Medical School in Madison. The cells were discovered in 1995 by accident as assistants in Allen-Hoffmann’s skin-researching lab sorted through old Petri dishes; the immortal cells stood out amongst mostly dead skin cell cultures, and upon further testing, proved to survive far longer than any other normal skin cell.

The article details an important and intriguing innovation considered by Allen-Hoffmann and her company, Stratatech, regarding the practical usage of these immortal cells; she proposes the idea that the cells could be mastered to fabricate swatches of skin for use during skin graft operations. This would be a major advancement in the field, as presently, the effectiveness and reliability of the procedure for skin grafting has not been perfected. Although this proposal is a fascinating one, the article mentions the bare minimum regarding the origin and nature of the cells themselves—they are collected from the foreskins of circumcised babies— and neglects to describe what factors could possibly incite such consistent growth. Information regarding the mechanism and function of these cells is very hard to find, as inventor Allen-Hoffmann has kept her secrets under wraps.

Even so, Allen-Hoffmann patented her special cells in 2005— a slightly more detailed description regarding her cells was given on the patent website. The cells, which are referred to as “Immortalized human keratinocyte cells,” are collected from cultures with both malignant skin cells and ‘spontaneously immortalized human keratinocytes.’ These cells produce keratin (an insoluble protein found in the outer layer of skin) and never cease dividing. [@http://www.patentstorm.us/patents/6884595.html]

Several of the current, most common methods for skin grafting are detailed in the article in a concise and helpful way. The author effectively frames the potential future of skin grafting and the sources of the grafts with appropriate history and background information. The largest human organ, the skin, is responsible for protection and insulation, and has two major parts: the outer layer, the epidermis, and the inner, flexible layer, the dermis. One of the most common methods of skin grafting for burn patients is called ‘split-thickness skin grafting,’ where the doctor takes a piece of skin from another part of the body and transplants it onto the affected area. Epicel, a patient-specific product that is grown in the laboratory, is a thin layer of epidermis that can be used to cover the burned area. Another engineered skin product on the market is called Apligraf— also produced from the cells of circumcised baby foreskins, this artificially-grown skin is often successful because the cells, with underdeveloped immune systems, are not likely to cause a rejection reaction in the patient. Even so, complications with healing and infection often arise.

The immortal cells discovered in Allen-Hoffmann’s lab are different, however. The advancement of these cells toward becoming an FDA approved product could revolutionize skin grafting; a graft with perpetually dividing skin cells would allow for the recovery of the skin to a full thickness and greater strength. Skin grafts would be available for patients who do not have enough remaining skin to undergo split-thickness grafting and would be more comprehensive than using an artificial skin product. The article raises concerns, though, regarding the cancerous nature of cells that never stop dividing—could these cells cause tumors to form in patients with skin grafts?

Biotechnology is constantly challenging the medical precedent, studying past procedures and trials, and searching for new information to formulate newer, better drugs and treatments. More significant than describing the specific treatment and development methods for artificial skin and skin grafts though, this article about ‘immortal cells’ sets the stage to question the limits of the field of biotechnology. The possibility for the development of cancer is certainly a controversial issue surrounding the potential use of these new cells. When searching for cures and advancements in the medical field, it can be difficult to tell where treatments stop being safely helpful and start being dangerous; risky surgeries, chemotherapy, and new drugs can all have negative effects that may end up outweighing the benefits. Although the trials where the immortal cells were grafted onto animal subjects have not produced any evidence of malignant developments, how can any researcher be sure that harmful results would not arise in human testing? It is one thing for a drug or treatment to be approved without full knowledge of possible, negative side-effects, but it is another thing entirely to approve a drug with known carcinogenic tendencies. Will it ever be acceptable to make a product with such blatantly unsettling traits available to the public?

On the other hand, although intentionally implanting cells that behave like cancer may seem like a careless gamble, it could turn out to be the best way to produce skin grafts with a high success and recovery rate. The only way to determine if such a technology will be positive and effective is to carry out trials and measure the results. A certain degree of trust and confidence must be placed in the judgment and skill of the pioneers at the forefront of biotechnological advancements such as this one. Could it be possible to harness dangerous, cancerous cells and use them to a medical advantage? Only time will tell.

-JG

Quality issues in skin banking: a review

Title: Quality issues in skin banking: a review
Author: J. N. Kearney
Source: Burns Magazine; Volume 24, Issue 4, Pages 299-305
Publication: June 1998

Article available at: http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T52-3TGMXTX-3&_user=
489286&_coverDate=06%2F30%2F1998&_alid=661624455&_rdoc=16&_fmt=summary&_orig=search
&_cdi=4990&_sort=d&_docanchor=&view=c&_ct=28&_acct=C000022678&_version=1&_urlVersion
=0&_userid=489286&md5=0f5f5184a35b8881d30c480ec0e2b920

In the world of healthcare and medicine, consistency, reliability, and quality are highly appreciated. Doctors and hospitals follow national guidelines and procedures, striving to provide the best care for their patients and taking action to improve the dependability and the success rates of their services. Pharmaceutical and biotech companies must also adhere to predetermined standards by which they must formulate and manufacture their drugs. Likewise, assistive medical organizations, such as skin banks which harvest and store skin, have been recently forced to set high goals in regard to the quality of their ‘product’ or ‘service:’ the allocation and administration of skin for grafting.

In the June 1998 issue of the scientific journal, Burns, J.N. Kearney’s article, “Quality issues in skin banking: a review” explores the current, extensive checks and balances placed in the skin banking system to ensure the maintenance of safe and effective skin grafts. The article lends extensive insight into the depth and seriousness of the precautionary measures taken in the process of skin collecting and storage.

The history of tissue and skin banking standards is intriguing; up until as recently as 1993 in the USA, the government had created no national standards for the routine practices or upkeep protocol in an establishment such as a skin bank. By 1997, however, firm rules were set by organizations that met expressly to form those guidelines: the American Association of Tissue Banks (AATB) and the American Red Cross in the USA. The Food and Drug Administration also became involved in inspecting the banks, their records, and especially their methods for testing potential donors. Now that a standard system has been established, though, the 30-50 nationwide skin banks must adhere to a type of ‘quality framework’ in order to regulate administrative aspects such as staff education and the filing of records, as well as the medical aspects such as the thoroughness of donor testing and the consistency of environment for skin storage. Like major pharmaceutical companies, these skin banks must also adhere to GMP’s— Good Manufacturing Practices.

The article details the methods involved in testing for risk-factors such as cancer, HIV, Hepatitis B, and syphilis in both live and cadaver donors. The tests vary greatly in their process and target depending on the disease, and false results can often arise from the analysis of cadaver blood. The article also discusses the danger that lies in presence of bacteria and fungal flora on the grafted skin, and the sterilization techniques used to ensure successful disinfection. The skin must first be assessed for harmful bacteria, and then treated with an ‘antibiotic cocktail’ that is effective in removing abundances of microorganisms, but that will not eliminate the viability, or liveliness, of the skin cells. A distinction is clearly drawn between viable and non-viable skin samples; the viable skin can be expected to live and must be preserved using cryopreservation, while non-viable skin is non-living and is not stored with as much rigor. The viable skin grafts are stored in a cryoprotective agent, packed in sterile materials, and stored at a below-freezing temperature around -130 degrees Celsius. For non-viable skin, the goal is to remove the water during storage so as to avoid the degradation of the cells and tissue structure. To do this, either deep freezing or a process called lyophilization is used. The methods remove water from the skin cells to ice crystals and to the outer environment, respectively, in order to circumvent tissue breakdown.

But where did the impetus to create such a strict, regulatory system for tissue and skin banks arise? Published in 1993, Warren E. Leary’s article in the NYT, “US Moves to Regulate Tissue Transplant Industry,” effectively discusses the issues leading up to the tissue industry’s reforms. According to Leary, major attention was paid to the tissue banking system after 61 organs from a Virginian who happened to have HIV were distributed successfully to 40 different patients. When seven of the patients contracted the virus, there was an uproar; the government could see that the standardization of the system would be a necessity. Other issues due to improper shipment or handling of tissues before implantation arose regularly, further demonstrating the need for tighter controls on their harvesting, storing, and distribution. Soon after the publishing of this article, the four-year process of developing the rules and regulations for tissue and skin banks began.

“Quality issues in skin banking: a review” successfully illustrates and demonstrates the complexity of the skin banking system while making a point to emphasize the extreme nature of the guidelines forced upon these tissue establishments. However, further than the origin of the system’s reforms, another thing not adequately addressed by the review is effectiveness. Has the rate for bacterial or viral infection in patients with skin grafts decreased since the implementation of these rules? Have fever people contracted diseases due to less carelessness among skin graft harvesters and specialists? Are the national rules being effectively enforced? These are the most important questions to be asking, and yet, are not dealt with in this review or in any subsequent follow-up— in Burns, another major magazine, or a newspaper. Detailing the move toward a regimented, regulated system is certainly positive in terms of garnering awareness regarding the value of quality in the given medical area, but a report on the real outcome of this new set of standards would be even more revealing. As a patient should receive a follow-up appointment with her doctor after a major surgery or procedure, the medical community deserves a follow-up report to show the success of the major restructuring of the tissue bank system.

-JG