The body responds to a bone break with inflammation, and cells start to gather in the location of the break to form a hematoma. A soft substance called a callus replaces the blood clot within a week or two, acting as a sort of bridge to hold the pieces of the fracture together. The healing process is finished after the callus solidifies into bone over several months.
But occasionally, that connective tissue connecting the bones doesn’t develop, leading to a nonunion. Nonunions can be particularly crippling in individuals with long-bone fractures (of the tibia, fibia, or femur, for instance), greatly impairing their quality of life and capacity for employment.
Nonunions can be challenging for surgeons to diagnose because they require individualized evaluations of X-rays collected over a six- to nine-month period. The problem is that the bone might be healing, albeit extremely slowly; in that case, further treatment might not be required.
But if it doesn’t heal, the patient will have to have another surgery after months of suffering and restricted activity. Surgeons would have a tool that could detect nonunions earlier in an ideal world.
“The end goal is to save patients time, money, and frustration,” says Brendan Inglis, a Lehigh University graduate student in the Department of Mechanical Engineering and Mechanics. “Because if the surgeon comes back to you and says you have a clinically diagnosed nonunion, and you need further interventions, that’s going to further delay your ability to get back to your life.”
Inglis is the primary author of an article that was just published in Scientific Reports that demonstrates how the mechanical stiffness of the entire bone is determined by the healing zone’s dual nature as soft and hard material.
As researchers, we often read a great paper, and come across a value we’ll be curious about, and the citation just points us to another paper, which points you to another paper, and so it becomes this whole rabbit hole effect. This app is a nice way to visualize what we did and build it into your own research. I think in an ideal world, there will be more sharing of information like this because, in the end, that’s the purpose of doing research.
Brendan Inglis
The project is based on research done at Hannah Dailey’s lab at Lehigh University’s P.C. Rossin College of Engineering and Applied Science. Hannah is an assistant professor of mechanical engineering and mechanics.
The team has previously demonstrated the potential of employing a virtual biomechanical test that is based on imaging to monitor the development of fracture healing. Using virtual biomechanical testing, the team has also created and validated a method for assigning material qualities to whole ovine bones.
Because some of the callus is still too fragile to be portrayed as bone, the virtual tests, according to Inglis, overestimated the mechanical capabilities of the bone early in the healing process.
“When we applied that model to the fractured ovine tibia, essentially a sheep’s lower leg, the mechanical properties didn’t match,” he says. “Our hypothesis was that all the soft tissue and cartilage involved in the healing of a fractured limb was being overpredicted, meaning the callus was being assigned properties that were too stiff.”
In other words, the previous model was inaccurate in its ability to distinguish between callus and bone. It could signal that the bone was healing more quickly than it actually was if the callus was treated as being stiffer than it truly was.
“Callus is a highly heterogeneous tissue, meaning it contains more than one density and stiffness value,” says Inglis. “So if you’re going to model an operated limb, you can’t treat everything as dense bone. You need to come up with some way to treat callus differently. But the mechanical properties of callus still aren’t well understood, and there wasn’t anything in the literature that set the cutoff point between where you start treating the healing zone as soft tissue, and where you start treating it as bone.”
To determine that cutoff, Inglis and his team worked with collaborators at the Musculoskeletal Research Unit (MSRU) at the University of Zurich. The Swiss researchers used a torsion tester to measure torsional rigidity in excised sheep tibia, and the Lehigh team used the corresponding CT scans and data to replicate those biomechanical tests virtually.
Inglis explains that the brightness of the pixels within the CT bone scans correlates to density. The brighter the pixel, the stiffer that area of bone.
“You can imagine that from a black pixel to the brightest white pixel, there’s a whole spectrum of values. So essentially what we did was find the cutoff below which the pixels are getting darker and should be treated as very soft. We postulated that prior to this study, those darker pixels were being calibrated too high, and assumed to be too stiff in the model.”
They optimized a cutoff point for separating soft tissue from the bone using a piecewise material model.
“When you get that density cutoff right, the virtual models can accurately replicate the rigidity you get from a bench biomechanical test of that same bone,” he says. “Once you have a model that’s validated to what was done on a bench test, you can start to predict different things about the behavior of healing bones. And the more we understand why the healing process fails, the better our chances of creating a tool that could one day inform surgeons. So this model gives us a foothold into one day translating this work into the clinic.”
To illustrate their findings, Inglis created an app that allows others in the field to interact with the data.
“As researchers, we often read a great paper, and come across a value we’ll be curious about, and the citation just points us to another paper, which points you to another paper, and so it becomes this whole rabbit hole effect,” he says.
“This app is a nice way to visualize what we did and build it into your own research. I think in an ideal world, there will be more sharing of information like this because, in the end, that’s the purpose of doing research.”