Comparative medicine lab rejuvenates arthritis-inflicted joints

Watching a dog complete the seemingly rapid transition from puppy with boundless energy to adult hobbled by arthritis is a tough experience, just as it is when the dog’s owner experiences the gradual onset of knee pain and one day thinks, “Guess I can’t do the things I used to do when I was younger.”

The desire to spare both pets and owners from gradual decline due to osteoarthritis led James Cook, DVM, PhD, to start the Comparative Orthopaedic Lab at the University of Missouri-Columbia. The lab emphasizes the crossover between human and veterinary medicine, working to find orthopedic solutions that help people and animals.

One of the most talked-about research projects in progress at the lab is joint replacement using living tissue instead of metal and plastic. Cook says the lab’s research could pave the way for durable, all-natural implants that turn back the clock on the body’s joints.

To give a better idea of what Cook and his team are working on, he began by telling a story about his grandfather.

A history of knee problems
Cook’s fight against arthritis began during his childhood, at the side of his grandfather who was fighting knee problems. His grandfather received one of the country’s first knee-replacement surgeries in the early 1970s, but the implant technology’s limitations meant that his grandfather would go on to endure eight total surgeries and spend his later years confined to a wheelchair.

Watching his grandfather endure multiple surgeries due to implant wear and loosening, an infection, and an implant failure led Cook to believe that modern medicine could do better.

“That always inspired me to try to do something better than metal and plastic, to try to come up with a biological solution to this problem that affects millions worldwide,” Cook said.

Right place, right time
Cook indulged his dual interest in veterinary and human medicine by earning his DVM and PhD at the University of Missouri-Columbia. Coincidentally, the medical school and veterinary school were within minutes of each other on the school campus.

Cook’s interest in comparative medicine met its match when Cook met a young faculty member named Keith Kenter, PhD, and the two soon sketched out their ideal lab on a restaurant napkin.

That lab officially opened in 1999 and has grown from a “closet” to a more than 2,000-square-foot space where 30 people - including faculty, staff, students, residents, and fellows - conduct research. According to Cook, the constant interaction between the university’s veterinary, medical, engineering, and bioengineering schools makes it possible to work faster and smarter.

“Not only are the logistics in place at Missouri to facilitate these interactions, but there’s a collaborative spirit here where everybody wants to work together and share information and try to make real progress,” he said.

This collaborative spirit has spurred research that could potentially redefine the treatment and prevention of osteoarthritis.

Forget metal and plastic, grow a healthier joint
Cook said that although metal and plastic joint implants have evolved since his grandfather’s days, they still have significant limitations. They wear out, break down, and loosen, and someone who gets a hip or knee replacement at age 40 could end up needing four or five revision surgeries because of implant deterioration over their lifetime.

Cook’s laboratory has spent the last 10 years researching a solution that completely removes metal and plastic from the equation: biological joint replacement.

Researchers begin by taking an MRI or CT scan of the joint and using that image to form a mold, which they fill with a “biological Jell-O” containing cells from organ donors. They create the articular cartilage surface, then exercise the new cartilage tissue using bioreactors to produce functional tissue engineered articular cartilage. Finally, they put the functional articular cartilage on a bony substrate, which surgeons implant into the joint.

Although this is a new way to approach joint replacement, Cook said orthopedic surgeons won’t have to worry about their day jobs when this technique becomes more common.

“It’s the same surgical technique, so we’re not putting hip or knee surgeons out of practice,” Cook said. “We would just give them a living biological implant to put in using the technique they’re currently doing with metal and plastic, then we’d resurface it with functional cartilage.”

The difference between the biological implants and their synthetic counterparts, Cook said, is that while metal and plastic implants have limited lifespans, “Ours are actually getting better over time because that cartilage can adapt just like when you were young, when you were developing - it can adapt to your activities.”

The lab has performed the procedure on clinical canine patients, and Cook said that patients have returned to full athletic function for activities such as running around at the dog park and catching Frisbees approximately 12 weeks after surgery. In humans, Cook said the recovery time might be closer to six months.

Biological joint replacement has worked well in dogs, and the lab hopes to try it in humans in coming years, Cook said. Because of the many steps that the lab has to take in its journey toward FDA approval, he projected that it could still be seven to 10 years “before it would be anywhere close to accepted for routine clinical use.”

Fulfilling a lifelong goal
Cook still has a long road ahead in his professional career, but he said his research for animals and humans has already brought him close to his goal of helping people like his grandfather.

“My ultimate goal would be someday to have people like my grandpa getting biological knees,” Cook said. “That would be the ultimate reward and culmination of my professional career. But, if I died or retired today, I’d be more than happy with what we’ve accomplished together as a team at the Comparative Orthopaedic Laboratory.”
This is the first article in a two-part series about osteoarthritis research at the Comparative Orthopaedic Laboratory at the University of Missouri-Columbia. In the second article, we’ll cover their discovery of biomarkers that can be used for early prediction of osteoarthritis.

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