Have Researchers Found a Cure for Arthritis?

The rabbit hopped.

That may not seem like much of a feat, considering the small mammals are naturally built to leap forth on their long, powerful hind legs. But it was quite an accomplishment for a rabbit with osteochondral defects in its medial femoral condyle—a.k.a., knee cartilage damage.

Any impairment to cartilage—the flexible connective tissue found on articulating joint surfaces—can trigger pain, inflammation, and some degree of disability to the affected bone juncture. Damaged, injured, or diseased cartilage also eventually can lead to arthritis in the joint.

Roughly one in four U.S. adults (23.7 percent), or 58.5 million people, are living with clinically diagnosed arthritis, according to Centers for Disease Control and Prevention (CDC) data. The condition is more common in women (23.5 percent) than men (18.1 percent), and more common among adults in fair/poor health (40.5 percent) than those in excellent/very good health (15.4 percent), CDC statistics show. Arthritis prevalence also increases with age: Seven times as many elderly Americans (aged 65 and older) were diagnosed with the disorder in the mid-2010s than those aged 18-49, the agency reports.

Arthritis is not limited to the human species, however. Most animals—rabbits included—can develop the condition, depending on age, size, breed, and activity levels (not unlike their homo sapien owners/admirers).

The cause of the hopping rabbit’s arthritis is currently unknown (or being kept under wraps). But the cause is not as important as the cure—or treatment, as Thanh Nguyen would rather deem it.

Nguyen is part of a UConn bioengineering team that successfully regrew cartilage in the rabbit’s knee using electrical signals. The discovery raises hopes the technique could one day be used to heal arthritic joints in humans.

There is no cure for arthritis, but it can be treated and managed through medication, exercise, therapy, total joint arthroplasty, partial/unicompartmental joint replacement, cartilage replacement, or through microfracture, in which tiny holes are drilled in the joint’s surface. The technique prompts the body to create new joint tissue, but the new cells—called fibrocartilage—are more like scar tissue than natural cartilage.

“…fibrocartilage covers the bone and is better than nothing,“ noted Charles Kwok Fai Chan, assistant professor of Surgery at Stanford University School of Medicine, “but it doesn’t have the bounce and elasticity of natural cartilage, and it tends to degrade relatively quickly.”

A chondrocyte transplant (cartilage replacement) can be risky, as it involves replacing damaged cartilage cells with healthy ones from the patient’s own body or a donor. Both sources can be dicey; removing cartilage cells from a patient’s own body risks injuring the harvest site, while importing it from elsewhere increases the chances of rejection.   

An ideal solution would involve naturally regrowing healthy cartilage in the damaged joint itself. Some researchers have tried amplifying chemical growth factors to induce cartilage growth while others have created a bioengineered scaffold for fresh tissue regeneration, but neither approach has produced meaningful results, either separately or in combination.

“The regrown cartilage doesn’t behave like native cartilage,” said Nguyen, Ph.D., a UConn bioengineer and assistant professor in the university’s Department of Mechanical Engineering. “It breaks under normal stresses of the joint.”

Nguyen and other UConn researchers investigating ways to regenerate cartilage found that electrical signals are key to normal growth. The researchers designed a tissue scaffold comprised of poly-L lactic acid (PLLA) nanofibers, a biodegradable substance often used in surgical wound stitching.

“This is called a piezoelectric polymer,” Nguyen explained on a recent Quirks and Quarks With Bob McDonald broadcast. “The special thing about this is when you walk or run, that kind of load technically is the driving force to make this material and produce this electrical charge.”

Natural joint movement causes the PLLA scaffold to generate a weak but steady electrical field that encourages cell colonization and cartilage growth. The process requires no outside growth factors or stem cells but, most importantly, the cartilage that grows is mechanically robust.

Nguyen’s team recently tested the scaffold in a rabbit with an injured knee. The rabbit (age and breed unknown) was allowed to hop on a treadmill to exercise after the scaffold was implanted and, as predicted, the cartilage grew back normally.

“Piezoelectricity is a phenomenon that also exists in the human body. Bone, cartilage, collagen, DNA, and various proteins have a piezoelectric response. Our approach to healing cartilage is highly clinically translational, and we will look into the related healing mechanism,” said Yang Liu, a postdoctoral fellow in Nguyen’s group and lead author of the published research in the journal Science Translational Medicine.

Despite the promising results, Nguyen remains cautious knowing more testing is needed. “This is a fascinating result,” he said, “but we need to test this in a larger animal.”

And older animal. Since arthritis generally is an age-related condition, any new treatments or solutions—piezoelectric or otherwise—must conquer the age-specific healing barriers induced by older, more mature cells.

Calling all chimpanzees.