When it comes to healing the terrible wounds of war, success may hinge on the first blood clot - the one that begins forming on the battlefield right after an injury.
Researchers exploring the complex stream of cellular signals produced by the body in response to a traumatic injury believe the initial response - formation of a blood clot - may control subsequent healing. Using that information, they're developing new biomaterials, including artificial blood platelets laced with regulatory chemicals that could be included in an injector device the size of an iPhone. Soldiers wounded in action could use the device to treat themselves, helping control bleeding, stabilizing the injury and setting the right course for healing.
Formation of "designer" blood clots from the artificial platelets would be triggered by the same factor that initiates the body's natural clotting processes. In animal models, the synthetic platelets reduced clotting time by approximately 30 percent, though the materials have not yet been tested in humans.
"The idea is to have on the battlefield technologies that would deliver a biomaterial capable of finding where the bleeding is happening and augmenting the body's own clotting processes," said Thomas Barker, an associate professor in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University. "Simultaneously, the material would help instruct the biochemistry and biophysics of the clot structure that would govern subsequent healing."
Barker is scheduled to present information on the research Friday, Feb. 15 in a briefing at the annual meeting of the American Association for the Advancement of Science (AAAS). The research has been sponsored in part by the National Institutes of Health (NIH), by the U.S. Department of Defense through the Center for Advanced Bioengineering for Soldier Survivability at Georgia Tech, and by an American Heart Association postdoctoral fellowship to Ashley Brown, a postdoctoral fellow working on the project.
After an injury, the most critical need is to stop the bleeding. But as traumatic injuries heal, they often produce significant scarring that is difficult to treat. Georgia Tech researchers are working on both sides of the problem, developing cell signaling techniques that may head off the formation of scars - as well as techniques for addressing the fibrosis that is often the long-term result. Beyond helping halt the bleeding, the synthetic platelets would deliver regulatory chemicals designed to prevent scarring.
"The blood clot actually ends up directing how the entire wound healing process is going to occur," Barker said. "The initial clot matrix instructs very specific cellular behaviors which have consequences for the next wave of cells that comes in to do specific jobs, which have consequences for the next wave of cells. If we can modify that initial clot, it can become the three-dimensional matrix needed to build the regenerated or repaired tissue."
The synthetic platelets, made from tiny structures known as hydrogels, could be injected into the bloodstream where they would circulate until activated by the body's own clotting processes. Once activated, the particles - which are about one micron in diameter - would change shape, converting to a thin film that would help seal wounds. To develop these hydrogels, Barker is collaborating with Andrew Lyon, a professor in Georgia Tech's School of Chemistry and Biochemistry.
The bloodstream contains proteins known as fibrinogen that are the precursors for fibrin, the polymer that provides the basic structure for natural blood clots. When they receive the right signals from a protein called thrombin, these precursors polymerize at the site of the bleeding. To prevent unintended activation of their synthetic platelets, the researchers use the same trigger.
The researchers followed a process known as molecular evolution to develop an antibody that could be attached to the hydrogels to cause their form to change when they encounter thrombin-activated fibrin. The resulting antibody has high affinity for the polymerized form of fibrin and low affinity for the precursor.