When a patient breaks a bone, there's a possibility the fracture won't heal properly or quickly even with the aid of pins, plates or a cast.
The use of another restorative tactic known as bone morphogenetic proteins, or BMPs, is increasingly less likely. Designed to promote spinal fusion and bone repair more than a decade ago, these molecules can overperform, cause excessive or misdirected bone growth, studies have shown.
But because bone-healing biological research has often been limited, few other options exist.
"Novel therapies have gone underdeveloped because of this assumption that bones heal without a problem," says Kurt Hankenson, a professor of orthopaedic surgery at Michigan Medicine. "The reality is there's a huge number of fractures that occur each year that don't heal very well."
The divide recently inspired Hankenson and a team of scientists from other institutions to examine a new therapeutic approach.
Their method: deliver additional Jagged-1 - a potent osteoinductive protein known to activate the Notch signaling pathway that regulates bone healing at the spot of a bone injury.
"We've hypothesized for many years that by binding the Jagged-1 to a biomaterial and delivering it to a bone injury site, we could enhance healing," Hankenson says.
The results, published in npj Regenerative Medicine, affirm that hunch: Rodents that received Jagged-1, applied via wet collagen sponge, saw improvements to the skull and femoral bone injuries.
Rodents treated with BMPs, by contrast, also benefited but developed the same problematic bone hypertrophy associated with human use of those proteins.
These findings suggest that the former therapy could one day benefit people.
It's not fully known why some bones don't heal the way they should -- nor do scientists know whether a genetic component plays a role, Hankenson says.
This much is clear: People with metabolic dysfunction, such as diabetes, have greater odds of poor healing after a fracture. So do the elderly, who are also prone to more bone injuries because of lower bone mass, such as osteoporosis. Those suffering severe trauma, regardless of age or prior health status, also are likely to face problems.
Although more research and funding are needed before the concept could be tested in humans, Hankenson says the early results offer some takeaways.
Those with serious breaks or fractures that would otherwise require autogenous bone grafting stand to benefit the most from supplemental Jagged-1 injections, he notes.
That's because such grafting, which involves using bone from elsewhere in the body, is a costly surgical procedure that can have secondary problems -- and has a higher morbidity risk.
Patients with slow-healing or nonhealing bones might also receive Jagged-1 well after an injury occurs, Hankenson says.
The delivery mechanism, using biomaterials to provide structure for healing, may also be refined.
Still, because medical costs for bone injuries nearly exceed $1 trillion annually in the United States, not to mention lost productivity from missed work or multiple surgeries, the impetus to find alternative solutions remains strong.
"We've been very motivated to develop new therapeutics to repair bone," says Hankenson, "and the approach we've taken to do that is to better understand the biology of healing."