In Third-Degree Burn Treatment, Hydrogel Helps Grow New, Scar-Free Skin

Johns Hopkins researchers have developed a jelly-like material and wound treatment method that, in early experiments on skin damaged by severe burns, appeared to regenerate healthy, scar-free tissue.

In the Dec. 12-16 online Early Edition of Proceedings of the National Academy of Sciences, the researchers reported their promising results from mouse tissue tests. The new treatment has not yet been tested on human patients. But the researchers say the procedure, which promotes the formation of new blood vessels and skin, including hair follicles, could lead to greatly improved healing for injured soldiers, home fire victims and other people with third-degree burns.

The treatment involved a simple wound dressing that included a specially designed hydrogel -- a water-based, three-dimensional framework of polymers. This material was developed by researchers at Johns Hopkins' Whiting School of Engineering, working with clinicians at the Johns Hopkins Bayview Medical Center Burn Center and the Department of Pathology at the university's School of Medicine.

Third-degree burns typically destroy the top layers of skin down to the muscle. They require complex medical care and leave behind ugly scarring. But in the journal article, the Johns Hopkins team reported that their hydrogel method yielded better results. "This treatment promoted the development of new blood vessels and the regeneration of complex layers of skin, including hair follicles and the glands that produce skin oil," said Sharon Gerecht, an assistant professor of chemical and biomolecular engineering who was principal investigator on the study.

Gerecht said the hydrogel could form the basis of an inexpensive burn wound treatment that works better than currently available clinical therapies, adding that it would be easy to manufacture on a large scale. Gerecht suggested that because the hydrogel contains no drugs or biological components to make it work, the Food and Drug Administration would most likely to classify it as a device. Further animal testing is planned before trials on human patients begin. But Gerecht said, "It could be approved for clinical use after just a few years of testing."

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John Harmon, a professor of surgery at the Johns Hopkins School of Medicine and director of surgical research at Bayview, described the mouse study results as "absolutely remarkable. We got complete skin regeneration, which never happens in typical burn wound treatment."

If the treatment succeeds in human patients, it could address a serious form of injury. Harmon, a coauthor of the PNAS journal article, pointed out that 100,000 third-degree burns are treated in U. S. burn centers like Bayview every year. A burn wound dressing using the new hydrogel could have enormous potential for use in applications beyond common burns, including treatment of diabetic patients with foot ulcers, Harmon said.

Guoming Sun, Gerecht's Maryland Stem Cell Research Postdoctoral Fellow and lead author on the paper, has been working with these hydrogels for the last three years, developing ways to improve the growth of blood vessels, a process called angiogenesis. "Our goal was to induce the growth of functional new blood vessels within the hydrogel to treat wounds and ischemic disease, which reduces blood flow to organs like the heart," Sun said. "These tests on burn injuries just proved its potential."

Gerecht says the hydrogel is constructed in such a way that it allows tissue regeneration and blood vessel formation to occur very quickly. "Inflammatory cells are able to easily penetrate and degrade the hydrogel, enabling blood vessels to fill in and support wound healing and the growth of new tissue," she said. For burns, the faster this process occurs, Gerecht added, the less there is a chance for scarring.

Originally, her team intended to load the gel with stem cells and infuse it with growth factors to trigger and direct the tissue development. Instead, they tested the gel alone. "We were surprised to see such complete regeneration in the absence of any added biological signals," Gerecht said. Sun added, "Complete skin regeneration is desired for various wound injuries. With further fine-tuning of these kinds of biomaterial frameworks, we may restore normal skin structures for other injuries such as skin ulcers." Gerecht and Harmon say they don't fully understand how the hydrogel dressing is working. After it is applied, the tissue progresses through the various stages of wound repair, Gerecht said. After 21 days, the gel has been harmlessly absorbed, and the tissue continues to return to the appearance of normal skin.

The hydrogel is mainly made of water with dissolved dextran -- a polysaccharide (sugar molecule chains). "It also could be that the physical structure of the hydrogel guides the repair," Gerecht said. Harmon speculates that the hydrogel may recruit circulating bone marrow stem cells in the bloodstream. Stem cells are special cells that can grow into practically any sort of tissue if provided with the right chemical cue. "It's possible the gel is somehow signaling the stem cells to become new skin and blood vessels," Harmon said.

Additional co-authors of the study included Charles Steenbergen, a professor in the Department of Pathology; Karen Fox-Talbot, a senior research specialist from the Johns Hopkins School of Medicine; and physician researchers Xianjie Zhang, Raul Sebastian and Maura Reinblatt from the Department of Surgery and Hendrix Burn and Wound Lab. From the Whiting School's Department of Chemical and Biomolecular Engineering, other co-authors were doctoral students Yu-I (Tom) Shen and Laura Dickinson, who is a Johns Hopkins Institute for NanoBioTechnology (INBT) National Science Foundation IGERT fellow. Gerecht is an affiliated faculty member of INBT.

The work was funded in part by the Maryland Stem Cell Research Fund Exploratory Grant and Postdoctoral Fellowship and the National Institutes of Health.

The Johns Hopkins Technology Transfer staff has filed a provisional patent application to protect the intellectual property involved in this project.

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Bioengineered Skin

Scientists at Universidad Carlos III de Madrid (UC3M -- Carlos III University) are participating in research to study how to make use of the potential for auto regeneration of stem skills from skin, in order to create, in the laboratory, a patient's entire cutaneous surface by means of a combination of biological engineering and tissue engineering techniques.

The ability to generate mice that can have part of their skin replaced with human skin allows in vivo studies to be carried out; these studies could not be carried out any other way, given that human volunteers cannot be used due to ethical considerations. (Credit: UC3M)

Skin is a tissue that naturally renews itself throughout our lives thanks to the existence of epidermic stem cells. "We have found that this regenerative potential can be preserved in vitro (in the laboratory) if the cells are joined and become part of generated skin using tissue bioengineering techniques," explains Marcela del Río, of UC3M's Bioengineering. The research group in which she participates, made up of scientists from the UC3M, from CIEMAT (the Center for Energy, Environmental and Technological Research) and CIBERER (the Center for Biomedical Research in the Rare Disease Network) of the Carlos III Health Institute, has been working with this type of adult stem cells for years, with the objective of using them to regenerate patients' skin.

The researchers have already been able to join together these epidermic stem cells into skin created by means of bioengineering, and they have observed that the cells preserve the regenerative potential that they normally have in our skin. That is, using a small biopsy from a specific patient, they can generate almost the entire cutaneous surface of that individual in the lab. "The regenerative capacity of epidermic stem cells in these conditions is overwhelming, and it leads to the possibility of using these cells as a target for even more complex protocols, such as gene therapy," indicates Marcela del Río, who is a professor in the new Biomedical Engineering degree program at this Madrid university.

Patches of healthy skin

In fact, these researchers have already demonstrated, at the pre-clinical level, that it is possible to isolate epidermic stem cells from patients with different genetic skin diseases, cultivate them and, using molecular engineering as a first step, incorporate the therapeutic genes into each patient's genome to take the place of the one that the patient does not have or that functions abnormally. Afterwards, in the second step, the stem cells would be assembled into patches ready to be transplanted onto the patients.

In recent studies, researchers have isolated stem cells from patients suffering from Netherton syndrome, a genetic illness characterized by an excessive peeling of the skin that leads to a loss of the barrier function of the skin, which inhibits the loss of fluids so that we do not become dehydrated, or which stops pathogens that can cause infections from entering our bodies. These patients have a neonatal mortality rate of between 10 and 15 percent; the molecular basis of this pathology lies in a mutation of one gene, known as SPINK-5.

This gene inhibits the production of a protein that controls the process of skin shedding, ensuring that it occurs correctly. "What we did in this case -- explains Marcela del Río -- was to transfer a normal SPINK-5 gene to a patient's stem cells and later use these cells to generate skin that could be transplanted to experimental models, such as mice."

The results, which were recently published in the Journal of Investigative Dermatology, were that human skin that was regenerated in these immunodeficient mice showed a completely normal peeling process, so that epidermic structure and function were reestablished. "These pre-clinical studies could be transferred to clinical practice in the medium term, and could become a therapeutic strategy for patients who might otherwise have no treatment available to them," concludes the researcher.

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Electronics On Your Skin Just Like A Tattoo

Smart Skin Researchers have built an electronic device with physical properties that match human skin. Such ‘epidermal’ electronic systems seamlessly integrate and conform to the surface of the skin in a way that is mechanically invisible to the user. 

           Someday soon, hospital patients won’t be hooked up to wires and monitors -- instead, electronic patches will be temporarily tattooed onto their bodies. Doctors will be able to monitor their vital signs without poking and prodding, and patients wearing neck patches will even be able to communicate with robots, who will translate throat muscle movements into simple speech.

          A new electronic skin patch  no more invasive than a temporary tattoo, marks a major breakthrough in human-machine interfaces. Tiny semiconductor circuits that stretch with the skin could be rubbed onto a person’s skin to monitor muscle activity, heart activity or even brain waves in real time without using bulky medical equipment.

         The epidermal electronic circuit is initially mounted on a super-thin sheet of soluble plastic and laminated onto the skin with water, just like a temporary tattoo. Once it’s on, it can bend, wrinkle and stretch along with a wearer’s skin — it doesn’t pop off or snap, which is no small feat considering this is a high-performance semiconductor. When it’s no longer needed, it peels off like a layer of sunburned skin. Check out the video below to see this in action.

         The devices adhere to the skin not with glue or static electricity, but close-contact atomic forces called van der Waals interactions, which are essentially invisible to the user. Adhesion lasts up to 24 hours, the researchers report.

         Researchers at the University of Illinois who came up with this device made circuits with a wide array of components, to prove it could work: sensors, LEDs, transistors, radio frequency capacitors and wireless antennas, according to UI. The devices can draw power from induction or even from mini solar cells. 

         Inventors say they could be used for various medical applications, especially sensors that monitor heart and muscle activity, which currently require conductive gels, tape and wires. To prove it, they measured electrical activity produced by the heart, brain, and skeletal muscles, they report in this week’s issue of the journal Science.

         Studying brain function in a normal environment is impossible now — to use an EEG, a patient would have to be in a lab setting or wear some type of complicated helmet — but the patch could make it possible. Or imagine a patient with a degenerative disease who cannot communicate, but could use the patches to connect with a computer.

      In a throat patch experiment, the patch was precise enough for the research team to differentiate several words. They were even able to control a voice-activated video game with better than 90 percent accuracy. 

      “The technology can connect you to the physical world and the cyberworld in a very natural way that feels very comfortable,” said UI electrical and computer engineering professor Todd Coleman, who co-led the research team.

             The circuits are made possible through novel fabrication methods that allow bendable versions of semiconductors that are brittle when in bulk form. The research team, which also included engineering researchers at Northwestern University, developed a new device geometry they call “filamentary serpentine,” according to a UI news release. The circuits of the various devices are fabricated as tiny, squiggled wires, as shown in the photo above. The circuits’ wavy shape allows them to bend, twist, scrunch and stretch while maintaining functionality. 

            “The blurring of electronics and biology is really the key point here,” said Northwestern engineering professor Yonggang Huang. “All established forms of electronics are hard, rigid. Biology is soft, elastic. It's two different worlds. This is a way to truly integrate them.”

                                                                                               

                      

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Pollutants Love Your Skin

 

Substances in our skin oil remove ozone from the air in indoor environments. Flakes of skin are major components of indoor dust. Ozone is a major component of smog, and exposure to it has been linked with a greater risk of lung irritation, asthma, heart attacks and death. 

         We shed skin constantly -- each of us replacing our outer layer of skin every two to four weeks -- and all of those skin flakes may help reduce levels of certain pollutants in indoor environments.

          Substances in human skin oil are significant components of indoor dust, a new study found. And those substances are known to remove ozone from the atmosphere. Just by sitting there, in other words, you help cancel out some of the ozone in the room.

          But floating flakes of skin might also do harm. Byproducts form as skin substances interact with ozone. Scientists don't yet know what the effects of those reactions might be.

           "These results are a reminder that humans leave their skin flakes in the rooms they occupy," said lead researcher Charles Weschler, a chemist at the University of Medicine and Dentistry of New Jersey.

"What one person sheds may be an allergy trigger or source of harmful microbes for another occupant," he added. "Keeping our indoor environments clean remains as important in 2011 as our grandparents told us two generations ago."

            Ozone is a major component of smog, and exposure to it has been linked with a greater risk of lung irritation, asthma, heart attacks and death. Removing ozone from the environment, on the other hand, can reduce those risks and scientists have long wondered how human skin might help.

            Ozone is quick to react with a few ingredients in human skin oils, including certain fatty acids and especially a substance called squalene. Previous research has shown that the simple presence of humans can reduce ozone levels in indoor situations.

            A simulation study, for example, found a plume in a region around the body where ozone levels were lower compared to other areas because of reactions with skin oil, said Glenn Morrison, an environmental engineer at the Missouri University of Science & Technology in Rolla, who led that work.

           In another study published several years ago, Weschler and colleagues used simulated airplane cabins to show that the skin of passengers works like a sponge to remove a large portion of the ozone from aircraft environments. But the study also found that these chemical reactions produce byproducts with unknown and possibly harmful effects on health.

          For the new study, Weschler's group looked at data collected as part of an ongoing project in Denmark that is investigating potential links between indoor environments and children's health problems, especially allergies and asthma. In particular, they focused on dust samples collected from the bedrooms of 500 kids, ages three to five, and from 151 daycare centers that those children attended.

               Almost every sample contained large proportions of squalene and cholesterol, the researchers reported in Environmental Science & Technology, suggesting that human skin flakes make up much of the dust that settles on indoor surfaces.

             And while skin cells contain more squalene than cholesterol, the researchers found the opposite ratio in dust. That might be because cooking and other activities also release cholesterol into the environment. It could also be because ozone in the buildings is sucking up squalene. This was the first study to look at skin-derived substances in indoor dust.

            The next question, Morrison said, is whether chemical reactions between skin and ozone make air quality better or worse inside buildings. Removing ozone should be a good thing. But byproducts produced by ozone-skin reactions are known to be strong lung irritants.

            For now, along with previous work, the new findings are "really revealing how the human body is a big part of influencing our environment," Morrison said. "This is a pretty important outcome if you are trying to understand ozone exposure and other things, because we're part of the equation and we've basically been ignored."

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