A Wichita surgeon is heading up a $1.6 million research project that promises new hope for soldiers with significant leg wounds. Advancements in the design of body armor are providing better protection for men and women serving in the armed forces, significantly increasing the odds of surviving combat-related trauma. Many injuries occur from explosive devices like landmines, though, resulting in substantial damage to legs. Survival often comes at an agonizing cost: amputations, limb shortening, and painful surgeries that yield limited results.
So-called bone putty may offer an alternative that would revolutionize treatment and drastically improve quality of life. There is much to still be learned, and testing on humans is several years away at best, but Michael Heggeness at the KU School of Medicine-Wichita is determined to shepherd through a study that he thinks will revolutionize healing.
“Injuries now are different than they have been in previous conflicts,” he said. “The Army wanted a solution to all of these folks who wind up with a blown limb and segments of bone missing that lead to amputations or multiple surgeries with agonizing rehabilitations that come up with a twisted, misshapen limb all too often. They want to know what to do with missing sections of bones. Our charge was to help them solve that problem.”
Heggeness, who has been the program director and chair of orthopedics at the KU School of Medicine-Wichita since January 2012, came to Wichita from the Baylor College of Medicine in Houston. During his time there, he received a $4.5 million grant from the federal Defense Advanced Research Projects Agency to study bone repair and explore the possibilities for more effective treatments. Essentially, they were tasked with learning how new bones can form. Noting that the lower limb is the worst place for a fracture to heal, he said that the project was a bit “out there” because all available treatment methods for bone damage are inherently complicated, with long healing periods and limited results.
Cultivating bone putty that could be used on the battlefield when soldiers are wounded was the original objective of the grant. The substance promised to harden and stabilize fractures while at the same time healing the actual bone itself.
The research team didn’t quite meet that objective by the end of its three-year study; biologically compatible putty that would stabilize and allow room for the bone to heal remained elusive. Yet, an alternative method for fast bone healing was discovered in rodents. Bridging segments in the femur and fibula, new bone formations were developing within two weeks after being injected with cells.
“We were making bone like crazy and healing fractures in remarkably short periods of time,” Heggeness said.
The method for producing this rapid growth was developed by the research team prior to the grant project. A virus vector introduced into cultured cells resulted in the production of a large amount of the bone growth hormone BMP2, a protein that Heggeness has said “has some magic to it.”
Researchers developed a gel containing bone growth cells that could be injected with a needle or implanted surgically.
While revolutionary in its effect on rats, it proved less effective on larger animals, primarily because those animals had pre-existing immunity to the virus vector, a trait common in most humans as well. When suppressing immunity, the researchers had some success in their approach.
“We need to demonstrate to the FDA that it can work there before anything can start on humans. That’s what this new grant will help us do,” Heggeness said.
With the new grant money, Heggeness’ team will test its method using two virus vectors for which human immunity is uncommon. They’ll begin with cell cultures and branch out to small and large lab animals. The goal is to be able to demonstrate healing in a large animal’s weight-bearing bone within two to four weeks. That data, likely to come from tests on sheep, is expected to be available in about a year. If it is, the team will ask the FDA to approve a human trial. Heggeness said a human study could be off the ground in as little as two years, and the new treatment available in possibily three to four years.
The need is critical, he said.
“Every major trauma center in North America, including the two here in Wichita, sees two or three patients that would be appropriate for this therapy a week,” he said.
Team members include John Peroni, a professor of large animal surgery at the University of Georgia; Frank Gannon, former chief of bone pathology at the Armed Forces Institute of Pathology; and Steve Stice, a molecular biologist also housed at the University of Georgia in the College of Agricultural and Environmental Sciences.