We take it for granted that cuts, bruises, and scrapes will heal over time, but chronic, nonhealing wounds are a major health problem for millions of people, and the slow pace of normal wound healing leaves the body open to life-threatening infections. Researchers at Tufts University are developing agents that, applied to open sores, could someday help chronic wounds heal successfully, and speed the normal healing process.
Cells on the move: Blood vessel cells are shown migrating from left to right in response to injury. The red label shows the structures that cells use to move around.
The wound-healing agents target angiogenesis, the process of blood vessel growth. “If you can’t build new blood vessels, it’s virtually impossible to heal,” says Ira Herman, the project’s leader and director of the Tufts Center for Innovations in Wound Healing Research. When tissue is damaged, cells migrate into the wounded region and then proliferate to form new vessels that supply oxygen and nutrients to the upper layer of skin. This is one of the processes that stall in chronic wounds.
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Two decades ago, Herman and colleagues first showed that an enzyme called collagenase, produced by the bacterium Clostridium histolyticum, could promote the healing process in cultured cells and animals. When added to cultured cells, it spurred the cells to crawl and grow faster. “It essentially created track stars out of laggards,” Herman says. Although humans also produce collagenase, the bacterial enzyme was more effective. The enzyme digests collagen, creating small protein fragments called peptides. The researchers believe that the peptides created by the bacterial enzyme cause a more robust response from cells.
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The researchers analyzed which peptides were unique products of the bacterial enzyme, and synthesized several of them to see if they could promote wound healing on their own. Herman says peptides would be easier than enzymes to produce and deliver as treatments. It would also be easier to control their effects, he says. In a paper published last September in Wound Repair and Regeneration, the team demonstrated that the peptides increase cell proliferation and angiogenesis in cell models that have multiple layers of cells to mimic the structure of skin and the underlying blood vessels. Herman says that the team has since had promising results testing the agents in animal models, and he hopes to move the technology toward human trials. He envisions that the peptides could be sprinkled over wounds as dry particles or suspended in a gel.
Robert Kirsner, chief of dermatology at the University of Miami Hospital, says that the work “lends insight into novel repair mechanisms, which, if capitalized upon, can hopefully lead to new opportunities for faster and better healing.”
Elizabeth Ayello, a nurse and wound-care expert at the Excelsior College School of Nursing, says, “What’s intriguing about this is it speeds up the healing,” which Ayello says could potentially reduce scarring and infections. Such a treatment could be used on battlefields or in rural areas that lack easy access to hospitals. The acceleration of healing, she says, is particularly exciting given the high costs and significant pain that wounds cause patients.
