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Biomedical engineer Lori Setton’s collaborative research is pioneering new ways of providing relief to those who suffer neck and back pain.

Professor Lori Setton (right) and collaborators, including Pranali Tambe (left), a visiting research associate, are looking at new materials for regenerating soft tissue, which could lead to new therapies for back pain. (Photo: James Byard)

Maybe it happened after you hauled a house’s worth of boxes to and from a moving van while helping a friend move. Maybe it startled you after a seemingly innocuous fender bender. Or maybe you noticed it after spending day in and day out — for years — hunched over your laptop keyboard.

Whatever the case, it is likely that you have experienced the agony of low-back pain. One study estimates that 80 percent of the U.S. ­population will experience a back problem at some point in their lives. And according to the 2010 Global Burden of Disease study, low-back pain is the top contributor to disability both in the United States and globally.

Lori Setton, the Lucy and Stanley Lopata Distinguished Professor of ­Biomedical ­Engineering, has made it part of her life’s ­mission to help solve this problem. Much of her research focuses on developing materials for soft-tissue ­regeneration, which could unlock a cure for many back problems. After a successful two-decade ­tenure at Duke University, Setton arrived at ­Washington University in summer 2015 to zero in on this issue. With the help of a new set of ­campus collaborators, her ­already remarkable work has risen to a new level.

The science behind the suffering

One of the most detrimental changes that ­contributes to serious low-back problems — as well as many serious neck problems — is time itself. As people age, many experience degeneration of the intervertebral disc, a complex soft tissue between the vertebral bones of the spine. This degeneration can be exacerbated by demanding physical work.

Compounding the problem is that, unlike many other cells in the body, cells in the intervertebral disc stop ­regenerating as we get older. (It’s why your back problem might never seem to go away, but your kid’s back heals quickly.) It’s a vexing problem for scientists and patients with low-back pain.

“Basically, we have these really large structures that support our entire body — our skeletons — but they have no means to regenerate or repair themselves,” Setton explains.

What’s more, as we get older, the environment for these cells in the intervertebral disc gets increasingly inhospitable, as oxygen levels dwindle and pH levels rise in the tissue. Together, these changes make it more difficult for even the remaining cells to thrive.

For years, scientists and medical device companies tried to solve this problem by simply replacing damaged structures with artificial ­materials, such as polymers including polyurethane. “We thought we could just develop strong materials, inject them and solve the problem,” Setton explains.

There was one troubling detail: It didn’t work. Again and again, researchers and medical device companies failed to find a solution that improved patients’ conditions. So they returned to the drawing board.

Scientists, including Setton, are now taking a new approach. “We’re asking different questions,” she says. “‘Why are these cells dying? And how can we get a cell in this [unfavorable] environment to survive and do its job?’ We’re becoming exceptionally interested in ways of using biology to make smarter materials that will survive in this very hostile environment.”

These types of questions are opening an ­entirely new field of research that leans on biology, chemistry and engineering — and offers a promising road ahead.

Built for a new kind of science

If there is anyone who is perfectly positioned to excel at this kind of messy, discipline-crossing research, it’s Setton. She earned a bachelor’s degree in mechanical and aerospace engineering from Princeton, then followed it up with master’s and doctoral degrees in mechanical engineering and biomechanics from Columbia University. It’s a background that gives her special insight into how our bodies work — and how they can be fixed when they break down.

Now she uses her expertise to understand why cells in our intervertebral disc regenerate when we’re young, and what they lose over time that prevents them from regenerating as we age.

During the past few years, for example, she and others have learned that certain proteins within the disc shift over time. One protein, called laminin, appears to be particularly important in early development: It exists in juvenile structures, but it’s absent in adults.

“We started to ask questions about the effect of reintroducing laminin,” Setton says. “So we built two- and three-dimensional polymers that are capable of presenting laminin back to these cells when we grow them in culture,” she says.

The process of building these structures — known as cellular engineering — is complex. First, she and her team take nonfunctioning cells from human subjects. Then they grow them in tissue culture wells (similar to petri dishes) that have been modified with specific proteins and polymers known as biomaterials. Once she and her team have grown the cells and introduced the laminin, they study them to see if the cells are reverting to juvenile behavior.

The results so far have been ­encouraging. “It’s been pretty exciting to see these cells ­[regain] a lot of the behaviors of the juvenile cells,” Setton says. “They become biosynthetically ­active, and they do a good job repairing [themselves] in this environment.”

Although it’s a long way from petri dish to clinical solution, it appears to be one very big step in the right direction.

“Steps like these are possible because of the combination of skills that Setton brings to the table,” says Aaron Bobick, dean of ­Washington ­University’s School of Engineering & Applied Science. After all, the real-world problems we face have never respected the artificial boundaries that humans place between engineering and medicine, biology and chemistry.

“Nobody told the tissue in your spine that it needed a mechanical solution or a biological solution or a chemical solution,” says Bobick, also the James M. McKelvey Professor. “It’s at this interdisciplinary boundary that the advancements happen, and a lot of what goes on in biomedical engineering requires those multidisciplinary efforts. Lori brings that all together in her laboratory.”

Read the full story in Washington Magazine.

Improving Medicine & Health

“It’s at this interdisciplinary boundary that the advancements happen, and a lot of what goes on in biomedical engineering requires those multidisciplinary efforts. Lori brings that all together in her laboratory.”

- Dean Aaron Bobick