In the recent movie Avengers: Age of Ultron, the supremely skilled archer Hawkeye suffers a major injury to his midsection during the opening battle. Hawkeye is quickly wrapped up and whisked back to superhero headquarters, where a bioengineer repairs the terrible wound, using a tool that scans and then prints a new layer of synthetic skin across the injured area. After a quick recovery, he is soon up and racing back into action.
If only wound treatment were that advanced in the real world. Unfortunately, effectively dealing with major wounds and burns, whether they stem from disease or the battlefield, remains a technical and scientific challenge.
A wound is a complex micro-environment packed with competing influences, from the agents dispatched by the body's immune response to the bacteria that cause infections. Standard bandages and dressings cannot always maintain the infection-free, moist, oxygen-rich environment required for a wound to heal. One often-cited example is the population of patients with severe diabetes who incur external ulcers on their feet; approximately 25% of diabetics suffer from a foot ulcer at some point in their lives, and these wounds are a leading cause of amputations.
Recently, scientists have begun working on new types of smart bandages capable of monitoring and even treating such chronic wounds. The research is still in the prototype stage, and the approaches vary, but these intelligent devices will be closer to miniature medical labs than advanced bandages: they will protect the wound, provide a scaffold on which new cells can grow, monitor the area for infections, wirelessly alert caregivers to changes in the status of the injury, and potentially deliver medications directly.
Chemist Conor Evans of the Wellman Center for Photomedicine at Massachusetts General Hospital compares the nascent technology to the life-supporting protective garb of the space-walking astronaut. "What we're trying to do is make a space suit for woundssomething that can go over a wound, keep it safe, and start to allow it to heal," he says.
The treatment of wounds has changed dramatically over the millennia, beginning with ancient Sumerians applying poultices of honey and animal fats to an injury, but the body's healing process has remained the same. First, the body attempts to stop bleeding through coagulation. Then inflammation takes over, followed by the proliferation of new cells, repair of the injured skin, and eventually the growth of new skin to cover the wound.
In the case of chronic wounds, the first step is not as much of a concern as the latter ones, during which bacteria and other factors conspire to slow or halt healing. One of the major areas of focus in smart bandage research is detecting biological warning signs of these problems. At Northeastern University, chemical engineer Edgar Goluch and colleagues are developing sensors designed to identify the presence of specific bacterial species.
Oxygen is another key metric: healing tissues consume large amounts of oxygen; without it, they die. This is one of the main reasons for diabetic ulcers and the chronic wounds that can result from bedsoresthe pressure of one's own body actually denies oxygen to the surrounding tissue.
Evans and his group developed a prototype bandage that measures tissue oxygenation through the use of oxygensensitive phosphores, or light-emitting molecules. When oxygen bumps into these molecules, it effectively dims the phosphores; in low-oxygen environments, "as oxygen decreases, it glows brighter and brighter," he explains. The result is a bandage that maps oxygen levels across the wound. Initially, the bandage had to be photographed to reveal the results, but now oxygen-deficient areas are visible to the naked eye. Evans says the ability to pinpoint these trouble spots could allow for a more targeted response.
Other groups, including a team led by Harvard University tissue engineer Ali Khademhosseini, are developing technologies to measure not just oxygen, but temperature, pH, and more. For diabetic patients who often lose feeling in their extremities and thus fail to notice a worsening wound, this kind of feedback could be extremely valuable; a smart bandage with such sensors could alert them to the presence of an infection.
The next step in the process is reacting to alarming information. Khademhosseini and his multidisciplinary team are building smart bandages that consist of a flexible substrate with embedded microelectronics and communications components, along with sensors and drug delivery mechanisms. Current prototypes are about a half-inch thick and six to eight inches long. They communicate wirelessly with smartphones and computers through low-energy Bluetooth, and a coin cell battery powers the bandages, affording them a lifetime of about one week. The group is also working to incorporate wireless charging through wireless power transfer technology.
In one prototype, low oxygen levels in the wound trigger a chemical reaction inside the bandage; the by-product of this reaction is oxygen, which then migrates out of the bandage and into the deprived area. Khademhosseini and his colleagues plan to conduct animal testing of this oxygen-releasing system, along with another that administers antibiotics. The goal is to graduate to human clinical trials within a few years. In the case of an actual patient, the bandage could wirelessly relay sensor data to a smartphone on a regular basis. An app could translate that raw data, then generate updates on whether the wound is healing or becoming infected, and relay this information to a physician for review.
"The system could transfer all the sensing parameters to medical staff, including the oxygen concentration of the wound (and) temperature," suggests Ali Tamayol, a bioengineer at Harvard who is also involved in the project. "They could then decide if things are going well or if they have to do something."
Yet Khademhosseini says the smart bandage could also be a fully closed-loop system, given the power of micro-processors and the relatively small amount of data to be analyzed. The system could be programmed so certain conditions trigger it to release oxygen molecules, while others spur the targeted delivery of antibiotics. Tamayol explains that you could define a critical range for pH, for example, and if those parameters were breached, then a particular drug could be released. "The system could understand and react," he says. "Ideally, it would all be automatic."
The final step, after warding off infection and maintaining the right oxygen, moisture, and pH levels, is allowing the skin to properly reform. One of the ways our bodies deal with a severe injury is through scarring, but scar tissue can be painfully taut and unnatural, especially in areas like the face. Harvard University biophysicist Kevin "Kit" Parker, an Army veteran, has seen this firsthand in U.S. soldiers returning home from Iraq and Afghanistan with severe craniofacial burns. "The scarring can be really terrible," Parker says. "They struggle to use their mouths and open and close their eyes."
"There's an ensemble of technologies that will be applied to wound healing, because every patient is different, and every wound is different, too."
The soldiers' struggles inspired Parker to search for a better alternativea dressing that would allow the skin to heal with minimal scarring. The key may be the material that actually comes in contact with the wound as new cells move in to replace the damaged ones. The skin cells benefit when there is a 'scaffold' in place, and Parker and his team found that a substrate made of precisely aligned nanofibers is an ideal material. Other scientistsincluding Tamayol and Khademhosseinihave tested this idea of using nanofiber dressings for wound healing, with positive results. Parker's group, however, has developed a new manufacturing technique, inspired by a cotton candy machine, that allows them to incorporate a wider range of materials into the nanofibers.
In their research of the literature on wounds, Parker and his colleagues learned about a protein called fibronectin that can accelerate the healing process and prevent scarring. The group incorporated some of this protein into its polymer-based nanofibers, then tested the hybrid material in animal models. The results have not yet been published, but the fibronectin seemed to accelerate the healing and prevent scarring in mice. The work is still in its early stages, but Parker is encouraged. "We want skin that's soft, almost like baby skin, so if you have craniofacial burns you can still move your mouth," Parker says, "and we think we've nailed it."
Eventually, Parker says, this new material could be incorporated into smart bandage technology, but he cautions there will not be a single cure-all device for chronic wounds and burns. Khademhosseini's group is developing a range of different prototypes for that reason, and none of the scientists are underestimating the difficulty of the problem they are working to address.
"Wound site biology is very complex," Parker explains. "There's a whole ecosystem in there before you even start talking about infections. There's an ensemble of technologies that will be applied to wound healing, because every patient is different, and every wound is different, too. We're coming up with one technology, but there's no silver bullet."
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