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Researchers at the Massachusetts General Hospital Burn Research Center are particularly interested in the role the body's metabolism plays in responding to a severe injury. Injuries caused by burns and serious tissue damage caused by severe trauma have effects that extend way beyond the skin's surface.

Skin is much more than a coating for the body. It is a living organ — the largest in the body — that contains immune cells, blood vessels, nerve cells, and many other protective components. Skin consists of multiple layers, and deep burns and severe physical trauma tear through the full thickness of skin. This leaves the body vulnerable to infections and fluid loss, both of which put an injured patient at high risk for further medical complications. Center researchers were the first to prove that as a routine clinical treatment, the critical first step is removal of the damaged skin followed by immediate covering of the wound.

Serious injury from burn and/or trauma affects many organ systems. Center researchers have long been interested in these body-wide changes. For example, they have discovered that after a burn, the body's metabolism goes into high gear, burning up to twice as many calories as usual. Compounding the serious issues of infection and fluid loss, a badly-burned body begins to turn on itself, consuming cellular components faster than the body can replenish them. Scientists believe that this "catabolic" effect is in some way related to an overall increased metabolic rate in burned patients. For some unknown reason, certain body organs such as liver and muscle are affected more than others. This is a major focus of effort for Center scientists, who are currently using sophisticated imaging technologies to evaluate metabolic differences between organs.

Even though a badly injured body has a higher metabolic rate, burning more calories than usual, overfeeding can cause even more problems. The role of proper nutrition in caring for injured patients is surprisingly complex. For example, scientists have found that administering too much of the natural sugar glucose intravenously to injured patients can lead to liver damage and breathing complications. On the other hand, giving an injured patient a high-protein, high-carbohydrate diet by mouth, or by a feeding tube that delivers nutrients directly to the stomach or intestines, can maintain body weight and lead to a better recovery. Research suggests that this is likely to be primarily due to the fact that most injured patients' digestive systems are relatively intact and can act as a barrier against infection. Center scientists are currently studying the amino acid metabolism, a key process in the body's production of proteins.

One of the reasons researchers suspect that a high-carbohydrate diet can speed recovery from injury is that these natural body sugars promote insulin production. Insulin, in turn, has a reverse effect on catabolism. Center researchers are actively pursuing the role of insulin in recovery from injury, especially the perplexing phenomenon of insulin resistance that can develop in severely burned patients.

Interestingly, another factor that influences a burned patient's metabolic rate is ambient temperature. Scientists have learned that a warm environment (82 to 91 degrees Fahrenheit) can also tone down the body's catabolic response. It is believed that this occurs because the body tries to compensate for water loss through burned skin by raising its core temperature. Increasing the temperature of the room appears to offset this response. Other factors also play a role: Pain and anxiety, for instance, can increase a burned patient's metabolic rate, making his or her condition worse.

With knowledge accumulated over the years, Center researchers are studying ways to counter the body's catabolic effects. Some of this research has revealed the importance of exercise after a burn. A comprehensive rehabilitation program that includes certain resistance exercises can markedly improve the recovery process of severely injured patients. Some natural hormones involved in growth can also help the body absorb important nutrients and amino acids (the building blocks for proteins). Scientists have discovered that giving injured patients growth hormone (available as a drug) improves wound healing and reduces scarring. In addition, when burned children are given growth hormone, researchers have observed positive, long-term effects on bone growth. Center researchers have also discovered that drugs that block the body's "fight-or-flight" stress response have been shown to improve outcome by protecting the heart, reducing metabolic rate, and preventing muscle loss. Current Center research efforts in this area focus on the molecular and cellular aspects of muscle weakness and severe muscle wasting.

The new Center funded in 2013 builds on the previous success and experience of our longstanding Burn Trauma Center. The focus of the Center has now shifted towards the implications of insulin resistance in the context of muscle wasting and is driven by the realization that insulin therapy has failed to reverse the pathophysiological derangements, thus necessitating new, cellular and molecular based approaches. Using newly analyzed gene and protein information from the Inflammation and the Host Response to Injury Glue Grant together with the focused projects, the Center researchers should be able to generate important and novel data to address the complex mechanisms resulting in muscle wasting and insulin resistance after burn injury. Advancing the understanding should provide the Center investigators with unique opportunities to develop effective therapeutic approaches to lessen the effects of two of the underlying clinical problems that often accompany major burn injury.

To learn about the development of artificial skin at MGH, click here.

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