Burns can happen in an instant—in an excruciating flash or a scalding splash. But after the first searing of the flesh, it's the debilitating scarring that some burn survivors develop that can have the greatest long-term impact on their lives.
For doctors and researchers who examine how the body responds to burn trauma, the real issue is not that scarring can occur—it’s that the degree of scarring can vary greatly from one person to the next. "We don't know why some people get scarring and others don't," says Dr. Edward Tredget, Director of the Burn Centre and a Professor of Plastic Surgery at the University of Alberta in Edmonton. "People have struggled for years to find effective treatments for scars."
To search for the answers and provide new hope for countless burn patients, Tredget is using a CFI-funded mass spectrometer to look beyond the immediate wound to the cells and proteins involved in the body's overall immune response. Tredget hopes that once they understand how these cells and proteins behave, they can be manipulated into responding in a way that will limit scarring.
For some people, burns can pack a terrible double punch. Not only do these individuals have to deal with the initial injury and pain, they also have to contend with a second injury known as hypertrophic scars. These scars are thick, red, painful, fibrous mounds of tissue that are slow to heal. For people with extensive burns, hypertrophic scars can be highly disfiguring and severely limit their range of motion. The traditional way of trying to limit hypertrophic scars has been to treat them locally, says Tredget, who also leads the U of A's Wound Healing Research Group. But that doesn't always produce the best results. "It appears that there's a circulating immune response that is activated after a burn," says Tredget. "So even if you dampen things locally in the tissues, there are still cells that are activated and infiltrate the wound and contribute to the scarring."
The challenge is to find out how to manipulate the circulating immune response—not an easy prospect since the response involves hundreds of cells and proteins, many originating far from the wound site and carried to the wound via the blood. "A mass spectrometer enables us to pick out a single molecule—from a zoo of other molecules circulating in the burn patient's plasma—with very high levels of specificity and sensitivity," says Tredget.
Hypertrophic scarring is closely related to other so-called "fibroproliferative" disorders, such as pulmonary fibrosis. In these disorders, it's known that bone-marrow-derived stem cells, called fibrocytes, stimulate the production of collagen-based tissues. Fibrocytes are normally present in very small quantities in the skin. But in scar tissue, there are five times as many fibrocytes.
To study the impact of these fibrocytes on scarring, researchers need a way to watch their behaviour. Tredget and his colleagues, Dr. Aziz Gharary and Dr. Paul Scott, have identified and sequenced a unique protein marker that acts as a molecular sign post for this cell. The marker is essential because researchers can now quantify and track these cells in patients.
For many burn patients, the pain of healing is like a low-temperature simmer. The hypertrophic scars that develop are in themselves extremely itchy and painful. "Patients with severe hypertrophic scarring will only sleep for a few hours a night because they're so uncomfortable," says Dr. Edward Tredget, Director of the Burn Centre and a Professor of Plastic Surgery at the University of Alberta in Edmonton.
Tredget and his colleagues in the U of A's Wound Healing Research Group are using a CFI-funded mass spectrometer to identify the molecules involved in this painful scarring. The research is opening up new avenues to help limit scarring and drown out the related discomfort. The group is currently in "Stage III" trials, to be completed this year, with about 20 burn patients at the University. They are examining the role of Interferon alpha 2b in limiting the action of histamines in scarring. Histamines are chemicals that are a major part of the body's immune response to injury. They are excreted in large quantities from immature burn scars and appear to stimulate hypertrophic scarring and the associated pain and itchiness.
The initial results of the Interferon alpha trial are promising. They indicate that the Interferon treatment might lead to softer, flatter, less itchy scars that are also less disfiguring. The Wound Healing Research Group has previously shown that Interferon alpha 2b applied on the surface or under the skin reduces a burn patient's overall histamine levels. It may also reduce the activity of fibrocytes (cells that induce hypertrophic scarring) at the wound site.
Tredget says mass spectrometry is an essential tool for studying the action of Interferon in burn patients. "The ability to measure the theory that Interferon seems to make a difference biochemically is supporting our clinical measurements," he says.
The Wound Healing Research Group consists of Dr. Edward Tredget, his colleagues Dr. Aziz Gharary and Dr. Paul Scott, and Research Nurse Heather Shankowsky, RN. The group is also supported by funding from the Canadian Institutes of Health Research (CIHR).
The American Burn Association (ABA) is one of the world's leading organizations promoting burn-related research, rehabilitation, education, and prevention.
The Alberta Burn Rehabilitation Society (ABRS) provides support and assistance to burn survivors, their families, and friends.