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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But the most difficult challenge for any tissue-engineering project is identifying the proper ingredients to stimulate growth. This is where Mao and his colleagues proved to be innovators. At the time they began working on the project, most tissue engineers thought it was necessary to populate a scaffold both with a patient’s stem cells, harvested from bone marrow, and with proteins called growth factors, which tell stem cells how and when to form different types of tissue. Scientists would typically let these ingredients incubate in a scaffold before implanting the device so that a thin veneer of laboratory-grown tissue would envelop it first.

“The number-one obstacle you face is the host’s body rejecting newly engineered tissue,” says Mao. “You have to get over that initial hump for the long-term benefits of tissue engineering to pay off. And the way to do that — the thinking has always been — is to do as much of nature’s work as possible in your laboratory ahead of time.”

Mao’s team discovered a better approach. Just a year before the researchers began work on the meniscus, they successfully regenerated damaged cartilage in the joints of rabbits using scaffolds seeded not with stem cells or in vitro flesh but a single protein. With just the right protein in a scaffold, the researchers showed, the animal’s body would accept the device and dispatch its stem cells to build the desired tissue from scratch.

Watch video of Mao discussing his research.

“This was really a major breakthrough, promising a quicker, safer, and more reliable method of tissue engineering,” says Francis Y. Lee, a professor of orthopedic surgery and director of the Center for Orthopaedic Research at CUMC. Among the potential benefits of Mao’s approach, Lee says, is that it could generate functional tissue in less time than conventional tissue-engineering techniques. This is because it doesn’t require harvesting and culturing a patient’s stem cells in a laboratory, which can take several weeks or even months. Furthermore, Mao’s approach eliminates the risk of a patient’s stem cells being contaminated in a lab, which can disrupt the new tissue’s development and lead to its being rejected by the body. Says Lee: “Clearly, anything we can do to make the process more patient-friendly will push the field forward and be good for medicine.”

A 3D printer in Jeremy Mao’s office can produce a replica of a meniscus in about thirty minutes. This honeycombed polymer scaffold is then seeded with proteins and implanted into the knee, where it will encourage the body to grow a new meniscus. / Photos by Jeffrey SaksBut was Mao’s approach suitable for larger mammals? Last year, he approached Scott Rodeo, an orthopedic surgeon at New York City’s Hospital for Special Surgery, and Lisa Fortier, a veterinary scientist at Cornell University, to conduct a trial of his meniscus-regeneration technique on sheep. At Cornell’s veterinary hospital, several sheep underwent a procedure that Mao has long envisioned providing for people. First they each had an individually tailored 3D scaffold created for a new meniscus. Next, two growth factors were embedded in the scaffold. Finally, the devices were surgically implanted in the animals.

“Then you watch carefully — for months,” says Mao. “Will the scaffolds be rejected? Will the sheep show discomfort? Will their knees be unstable?”

This past winter, Mao, Fortier, Rodeo, and three colleagues in Mao’s lab published a paper in the journal Science Translational Medicine showing that the 3D-printed scaffolds performed beautifully in sheep. The first animals they treated developed normal-looking meniscuses within three months. A video on the journal’s website shows the sheep putting weight on all four legs and scampering around without a limp.

This year, after making minor adjustments to their technique, the researchers successfully operated on several more sheep. Based on the positive results, Mao and Rodeo are now seeking FDA approval to try out the procedure on human patients, which they are hoping to do within the next year or two. Mao says that he is already receiving e-mails and phone calls from people eager to participate in a trial. Many of them have seen news reports about his team’s progress; others have heard through patient networks that a novel solution to their chronic pain may be on the horizon.

“It’s been a reality check for me to realize how much clinical need there is out there,” says Mao. “Patients like the idea of getting a replacement body part that is natural, and genetically their own.”

Ultimately, Mao hopes the techniques that he and his collaborators are developing will prove useful to researchers trying to regenerate other body parts. His team is already experimenting with the design of more-complex tissues, like teeth, arm and leg bones, and muscles and bones that could be used to reconstruct the faces of people injured in catastrophic accidents.

“We want to apply our discoveries to as many medical conditions as possible,” Mao says, holding a 3D-printed meniscus. “This small piece of cartilage is just the start.”

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