Ted Miclau never had an epiphany, a single moment when he knew he needed to work in the lab to become a better orthopedic trauma surgeon. But as he developed his surgical skills, including new ways to repair bones through small incisions, or "minimally invasive" procedures, he was plagued by a growing unease. "Orthopedic surgeons have had tremendous success as structural technicians for bones," says Miclau. "If we put the pieces back together with limited damage to the surrounding tissues and blood supply, the body takes over and does the necessary repair—most of the time."

It was the times bones did not heal that bothered Miclau. "Astonishingly, 5 to 10 percent of fractures don't heal in a timely way. "Orthopedic surgeons don't have good explanations for why. That's why we don't have reliably successful treatment options."

Of the seven million fractures that occur annually in America, about 500,000 will have problems healing. The societal and human cost of fractures is measured in billions of dollars annually, with considerable pain and suffering. Reducing all these costs by enhancing bone healing is the goal of Miclau's research.

In his laboratory, Miclau studies bone growth at the molecular and cellular level. Miclau and his staff trace how mesenchymal stem cells, or precursor cells, become bone or cartilage cells. Specifically, they focus their studies on the behavior of genes that regulate the development of cartilage and bone, the formation of new blood vessels (angiogenesis), and the conversion of healing skeletal tissues into bone (ossification).

In a rigid, well-stabilized fracture, mesenchymal cells at the injury site convert directly into bone. In a fracture where the bone pieces are not tightly held together and there is more movement at the fracture site, mesenchymal cells turn into cartilage to form a more flexible bone callus that eventually converts into bone. "Somehow the mesenchymal cells 'know' how best to differentiate and repair the fracture," says Miclau. "How do these cells respond to movement or differences in blood supply? We are not sure, but we are trying to find out."

It comes as no surprise that fractures in older children, with their rapidly growing bones, heal more quickly than fractures in adults. But Miclau points out that the real bone-repair champions are not children, but infants. "A fracture that takes a week to heal in an infant might take a month to heal for a child, and three months in an adult. If we could just learn what makes infant bones heal so quickly and somehow bottle it, we likely could reduce healing times for everyone."

Miclau and his colleagues know they need several more years of research before they may fully understand bone healing at the cellular and molecular level. One goal is to understand bone healing at the genetic level well enough to identify potential healing problems before they occur, and tailor treatment depending upon a patient's individual genetic make-up.

Miclau believes San Francisco General is one of only a few hospitals in the world where he could fill a similar double role as scientist and orthopedic trauma surgeon. Because of the presence of UCSF doctors like Miclau, San Francisco General Hospital is a leading trauma center and a leading research center—a place where the latest research results are translated into better patient care.

"My lab is a good example of how clinical work can guide research," says Miclau. "We're searching not only for ways to change the treatment of fractures in the future, but also for knowledge that we can use for our patients at SFGH and other hospitals right away."

Source: Michael Barnes