Helping Joints Regrow Themselves

A chemical-infused scaffold generates new tissue by attracting stem cells.

Today's titanium replacement joints work very well for 10 to 15 years, but replacing them after they've worn out is a challenge for both patient and surgeon. A team of researchers from Columbia University proposes a way around that problem: by implanting a scaffold that encourages the patient's own stem cells to regrow the joint.

Regenerating a joint: A joint-shaped scaffold (top) attracts many more stem cells when it is infused with a protein growth factor (second from bottom) than without (second from top). The bottom image shows natural cartilage. Credit: Jeremy Mao

In research published this week in The Lancet, the researchers demonstrate that the technology--a joint-shaped scaffold infused with a growth factor protein--works in rabbits. About a month after the implant, the animals began using their injured forelimbs again, and at two months the animals moved almost as well as similarly aged healthy rabbits. The study is the first to show that an entire joint can be repaired while being used.

"They used the potential of the body as a bioreactor, instead of doing everything in the petri dish," says Patrick H. Warnke, a professor of surgery at Bond University. Warnke wrote a commentary on the Columbia study for The Lancet. While the connection between bone and the titanium in existing implants wears out over time, the hope for this alternative approach is that the new bone formed by the stem cells will create a more natural and durable connection, and that the scaffold itself would disintegrate over time.

The procedure, so far tested only in rabbits, still has a long way to go before it could be used in people, according to senior author Jeremy J. Mao, and a half-dozen scientists not involved in the research. It's still not clear how well the approach would work for human-sized joints, or in animals, like humans, that put more pressure on their joints.

In the study, the researchers first imaged the damaged forelimb joint and then created a three-dimensional picture of it, explains Mao, a professor of biomedical engineering at Columbia University Medical Center. They used a bioprinter to "print out" a precisely accurate, three-dimensional copy of the joint, but criss-crossed it with tiny interconnecting microchannels to serve as a scaffold for new bone and cartilage growth. The surgical implantation was the same used to insert titanium implants in people, Mao says.

Thanks to the added growth factor protein, the rabbit's own stem cells naturally migrated into the scaffold and regenerated both the cartilage and the bone beneath it.

The success is somewhat surprising. "I wouldn't have thought in a normal weight-bearing joint that you could [replace the newly forming] cartilage while the joint is being loaded," says Howard Seeherman, chief scientific officer for tissue repair at Pfizer. Seeherman says he would have expected the cartilage to just wear off when weight was put on the joint.

The research reflects a new trend in tissue engineering. "People are starting to think that if you simply build the microenvironment inside the body, the innate cells may be able to take this microenvironment and make the tissue," says Ali Khademhosseini, a tissue engineering expert and assistant professor at Harvard Medical School and Brigham and Women's Hospital. The approach has several advantages, he says. It's impossible to re-create in a dish the array of signaling chemicals the body uses to generate the diverse cell types in different tissue, and it's much easier to get approval from regulatory agencies to implant a scaffold than whole tissue.

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Mao says he next wants to test the procedure in goats, which are a better model for human osteoarthritis than rabbits. Goats consistently put more of their body weight on their limbs. Though rabbits put weight on their forelimbs, humans put far more on their knees and hips, and it is not yet clear whether the procedure would survive such pressure.

Rabbits, particularly young ones, are also known for their regenerative abilities. Mao says the 23 rabbits used in the study were skeletally mature, and the three control rabbits--with injuries but no surgical repair--did not regrow joints. Rabbits who received the scaffold but not the growth factor saw some new growth, but not nearly as much as the ones who got the growth factor.