Joint Venture

Tissue engineers at CUMC are bending the idea of what's possible — by growing new cartilage and bone inside the body.

by Claudia Wallis Published Fall 2015
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A synthetic replica of a human meniscus, pictured here at about three times its actual size. The meniscus acts as a cushion between the femur and the tibia. / Photograph by P. Marazzi / Getty Images // Inset photograph by Rita Maas

A tiny miracle is taking shape in Jeremy Mao’s laboratory. The needle-tipped nozzle of a 3D printer zips back and forth, shooting out a thin stream of white polymer onto a piece of paper. What emerges, layer by layer, is a one-inch crescent the size and shape of a human meniscus — the tough, fibrous band of cartilage that serves as the knee’s shock absorber. This artificial body part is not intended as a mere replacement. It is something far more remarkable: an ingeniously constructed bridge to healing. Once implanted into an injured knee, it will give the body a foundation for growing a whole new meniscus.

The capacity to heal is one of the human body’s most amazing characteristics. But some parts of our anatomy — including cartilage, tendons, and ligaments in joints — have limited powers of self-renewal. That’s where medical researchers like Jeremy Mao step in. For the past fifteen years, Mao has been at the forefront of the interdisciplinary field of tissue engineering, which combines elements of cell biology, genetics, materials science, and biomedical engineering, all in hopes of enhancing the body’s regenerative powers. Mao, who trained originally as a dentist and oral surgeon in his native China, was drawn to tissue engineering because he thought that certain craniofacial conditions, such as painful disorders of the temporomandibular joint (TMJ), could be treated by coaxing a patient’s stem cells into repairing worn-out bones and cartilage in the jaw. His work at Columbia’s College of Dental Medicine, where he is the Edwin S. Robinson Professor of Dentistry and codirector of the Center for Craniofacial Regeneration, continues toward that ambitious goal; in recent years, however, Mao’s research has broadened to include the regeneration of bone, joint, and soft tissues throughout the body.

“People familiar with my tissue-engineering work are often surprised to hear that I’m a dentist,” says Mao. “Dentistry, I remind them, is about much more than teeth. A great deal of reconstructive and plastic surgery is performed on the mouth. It’s an intricate and complex region — similar to the knee.”

“Patients like the idea of getting a replacement body part that is natural, and genetically their own." — Jeremy Mao

Mao’s latest project is intended to address one of the most common of all human-joint injuries. Every year, hundreds of thousands of people in the US — and millions around the world — tear a meniscus, typically in a sports-related mishap or as a result of cumulative wear and tear. Many people just live with the injury, whose effects can include chronic pain, swelling, and instability. Approximately 750,000 a year in the US opt for surgery. Depending on the severity of the injury, a surgeon may suture the meniscus or remove it altogether. Many patients, regardless of the treatment, eventually develop arthritis in the affected knee.

“Artificial implants exist, but they have serious drawbacks and aren’t used very often,” says Mao, referring to synthetic replacements that are available in Europe and may soon be approved for use in the US. “The main shortcoming of an artificial implant is that it doesn’t mesh perfectly with what’s around it. So it might cause irritation to the surrounding tissues, it might prove unstable, and it might wear out even faster than the original meniscus and then need to be replaced again.”

A new meniscus grown from a patient’s stem cells, on the other hand, would be a genetic fit for that person — a true example of personalized medicine. “Maybe, just maybe, it will fit into the body just as nicely as the original,” says Mao. “This is the promise of tissue engineering.”

Jeremy Mao / Photograph by Jeffrey SaksMao, who leads an interdisciplinary team of about twenty scientists and engineers at Columbia University Medical Center, began looking for a way to regenerate a meniscus about five years ago. The basic approach he chose was one that many tissue engineers were already using in their fledgling attempts to help the body regrow bits of damaged bone, skin, and soft tissue: this was to fabricate an implantable scaffold upon which new tissue could take shape. Using a special high-resolution 3D printer, Mao and his colleagues made a meniscus scaffold out of a biocompatible material called polycaprolactone, which is also used to make surgical sutures. The scaffold was honeycombed with tiny interior channels, into which the scientists could inject a variety of biological ingredients to stimulate the growth of new tissue.

“The idea was for new tissue to grow throughout the scaffold, which would slowly dissolve,” says Mao. “It took us months to determine the optimal size and shape of the interior channels. The surface geometry had to be just right for cells to take root.”

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