FEATURE

Hearts & Bones

Gordana Vunjak-Novakovic is at the forefront of regenerative medicine. Can her laboratory-grown body parts really work?

by Adam Piore Published Spring 2012
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Within this two-inch plastic vessel, or bioreactor, Vunjak-Novakovic can mimic the physiological environment of a developing human jawbone / Photograph by John Loomis“The thing about cartilage is that it doesn’t connect to the body’s vascular system,” says Vunjak-Novakovic. “So from a technical standpoint, it seemed like the easy target.”

At the time, tissue engineers saw their primary challenge as determining the right mix of nutrients, minerals, and proteins to feed their growing cells. Even slight variations in the nutrient soup they injected into their molds had a profound effect. A little extra calcium, for instance, would signal to the stem cells to develop into bone.

“I think everybody assumed that was 99 percent of the game,” says Vunjak-Novakovic. “Could other factors be influencing these cells? Sure, perhaps. But the consensus was that if you had a well-shaped mold and the right nutrients, you were probably good.”

Vunjak-Novakovic, however, was reading a lot about systems biology at the time. She was fascinated to discover that many physiological systems — genetic, molecular, electrical, and mechanical — are interconnected in surprising ways. In particular, she noted that people immobilized in hospital beds for long periods of time often experience a weakening of their bones and cartilage. It seemed that physical movement was essential to the upkeep of these tissues. Was it possible, she wondered, that developing cells are also sensitive to movement?

This was an idea that many physicians and biologists had considered but never had the means to test. To do so, Vunjak-Novakovic conducted an experiment in which a piece of developing cartilage was periodically rotated upside down. After a few weeks, she tested its strength. She’d hit the scientific jackpot. “The improvement in its structural integrity,” she says, “was beyond what we’d imagined.”

This led to a technical innovation: Vunjak-Novakovic developed a plunger-like device that gently presses down on the chemical solution in which developing tissues are immersed, replicating the forces of movement experienced by stem cells in the body’s joints.

But the real advance was philosophical, Langer explains: “Since then, all tissue engineers have come to appreciate the need to consider lots of variables, besides the molecular factors. She helped inspire this shift in outlook.”

For her design of highly sophisticated bioreactors, or tissue molds, Vunjak-Novakovic was recently elected to the National Academy of Engineering, one of the profession’s highest honors. 

OPEN HOUSE

Vunjak-Novakovic, a gentle-natured and cheerful woman who speaks with a soft Slavic accent, came to Columbia in 2005 intent on moving her technology from lab bench to bedside.

She knew she was going to need help. By this time, all biomedical engineers had come to realize that creating tissues capable of functioning in the human body would be much more difficult than they’d initially anticipated. “Even the cartilage wasn’t working as we’d hoped,” says Vunjak-Novakovic, who today also is a professor of medicine at the College of Physicians and Surgeons. “One of the odd things about cartilage, which makes it surprisingly difficult to work with, is that it has no natural ability to repair itself. When your cartilage deteriorates, that’s it — it doesn’t regroup. We discovered that stem cells, once they begin to identify themselves as cartilage, will get lazy and stop growing, too.

"Why nature would create a tissue with no ability to repair itself is one of life’s mysteries. But this is true of cartilage, as well as brain, heart, and pancreatic tissue."
-Gordana Vunjak-Novakovic

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