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The good news is that today's soldiers have better body armor than ever before, which drastically improves their chances of surviving war trauma. The bad news is that they often survive with significant damage to their lower extremities from explosive devices. A Wichita surgeon is at the forefront of research that could repair weight-bearing bone in a fraction of the time it now takes. "What the military wants to know is what to do with missing sections of bone," said Dr. Michael Heggeness, M.D., Ph.D., who is part of a $1 million research project to solve just that problem. The worst place to heal a fracture Heggeness started in January as chair and program director of orthopedics at the KU School of Medicine–Wichita. He also works at the Robert J. Dole VA Medical Center. He came to Wichita from the Baylor College of Medicine in Houston, Texas, where he first received a grant from the federal Defense Advanced Research Projects Agency (DARPA) to look into bone repair. "These are the people who think big thoughts," Heggeness said of DARPA. "This was one of those 'out there' projects." All of the current methods for treating bone damage – from amputa- tion to limb shortening, bone grafts, and transfers – have major drawbacks ranging from total loss of limb function to extremely long healing periods, complications, and limited effectiveness. "The lower limb is probably the worst place to heal a fracture," Heggeness said. Opportunities … and challenges DARPA's original objective was the development of so-called bone "putty" that could be used in the field for wounded soldiers, hardening and stabilizing fractures while also promot- ing healing of the bone. As often happens in basic research, Heggeness and his team of collaborators were not successful in meeting the original goal. They were unable to develop biologically compatible putty that would provide stability and also realized that, even if they had been able to do so, the amount needed would leave little bone surface area from which healing could proceed. It might also be so bulky that it prevent- ed skin closure. However, Heggeness' team did find an alternative method of rapidly inducing bone healing. A protein for speeding bone growth Heggeness' group had developed a method of producing rapid bone growth prior to the start of the DARPA project. It involves introducing a virus vector into cultured cells, causing them to produce a large amount of the bone growth hormone BMP2 – a protein which Heggeness says "has some magic to it." (And also, Heggeness noted, some controversy.) Once the DARPA work was underway, the team developed a gel that let them control the placement of the bone- growing cells, either during surgical procedures or through injection with a needle. The gel can vary in thickness from a milk-like substance to a peanut butter-like paste. Animal testing shows some success The researchers had great success with small lab animals but ran into problems when they tried the experiment on sheep and swine, mainly because of the animals' preexisting immunity to the virus vector (a trait most humans share). After suppressing the larger animals' immunity, the researchers had more success. Going forward, Hegge- ness' team plans to test their method using two different virus vectors for which human immunity is rare. Eventually, they think they will be able to demonstrate healing in a large animal's weight-bearing bone within two or three weeks. The whole process is projected to take about a year, near the end of which the team will apply to the U.S. Food and Drug Administration for approval of a human trial . Next steps The researchers know that FDA approval of human trials can take time, due to concerns over possible harm to the subjects. One member of Heggeness' team, Dr. Frank Gannon, is former chief of bone pathology at the Armed Forces Institute of Pathology. Heggeness and Dr. John Peroni, a professor of large animal surgery at the University of Georgia College of Veterinary Medicine, handle the surgical procedures, with Heggeness traveling to Georgia to operate with Peroni. The fourth member of the team, Dr. Steve Stice, is an animal and dairy scientist, also at UGCVM, who creates and fine-tunes the virus vectors. In addition to DARPA, the researchers hope to attract a commercial partner at some point. They say they haven't closed the door on the initial bone putty idea, but feel their method is the best approach if they can find the correct virus vector with which to work. Heggeness said he, for one, won't argue over terminology. "I would call it a gel, not a putty, but there's not a big difference." In models, this method bridged segments in the fibula and femur with new bone formation in as little as two weeks. 20 21