Recruiting the body to help regrow new joints

Roughly 70 percent of patients who have arthritis are 65 years old or younger. Yet the average life span for the metal joints commonly used by orthopedic surgeons is just 10-15 years.

Columbia’s Jeremy Mao thinks he may have found a solution to the problem. Using cutting edge bio-printers and a commercially available protein, the veteran inventor has found a way to recruit the body’s own stem cells to help re-grow the joint.

“We need to do clinical trials to demonstrate efficacy in patients, and get FDA approval,” he says. “If both are positive, this has the potential to replace metal implants.” 

It’s just the latest promising breakthrough from Mao, professor and Zegarelli Endowed Chair at Columbia University Medical Center. Trained as an oral surgeon, Mao practiced for years before deciding to seek a PhD in bioengineering because “I began to feel there was more to life.” 

Since earning his PhD, he has filed more than 60 patents for technologies ranging from a pair of molecules that reduce surgical scar formation by inhibiting the cells that create scars, to a technology that can stimulate the body’s own cells to make fillers – which could eventually eliminate the need for Botox or collagen treatments.

Mao’s latest invention has the potential to revolutionize joint replacement surgeries. 

Using 3-d imaging to model the healthy foreleg of a rabbit, Mao created a computer model of a reconstructed joint, and then used a 3-d bio printer to create a scaffold-like model of the leg out of biocompatible materials. Mao’s scaffold contained internal “micro-channels,” that could serve as conduits for blood vessels that he hoped would grow into the artificial joint.

Initially, Mao planned to implant stem cells into the scaffolding, in the hopes they would regenerate the joint. But that approach would require surgeons using the device to receive training in how to insert the stem cells and increase regulatory issues if the technology was ever ready for widespread use. 

Mao hit upon a better solution when he inserted a commercially available protein generally used for research purposes called TGF beta 3 into the micro channels. The protein, his team discovered, actually recruited the host’s own stem cells, which began to regenerate the joint.

Mao implanted the protein-infused foreleg scaffolding in the leg of a rabbit, and within 6 weeks, the rabbit was walking normally.

The technology could be used for a wide variety of other surgeries. Mao has already used similar scaffolding technologies to replace missing teeth in rats, re-growing 22 rat incisors and human molars (by surgically inserting them into the backs of the rats) in just nine weeks. 

“We are working at the interface of stem cell biology and tissue engineering and trying and move science from the Petri dish to patients,” Mao says.

Mao has a number of other promising research projects underway. Among them: A new way of doing root canals. 

Currently, dentists drill a hole in a tooth, remove infected pulp tissue, and insert a bio-inert material. Though the technique solves the pain problem, the tooth eventually dies, and turns dark and so brittle it is vulnerable to facture. 

Mao’s technique would instead deliver proteins to the tooth that could regenerate the pulp. 

“If you practice dentistry, you help one patient at a time,” says Mao, who continued to see patients until his research load became too time-consuming four-and-a half years ago. “But if you try to build technologies, you can help millions of patients at a time. That’s something incredibly powerful for me.”

To view technologies from Dr. Mao's lab, please click here