Frank Petrigliano, MD, (left) and Denis Evseenko, MD, PhD CREDIT USC Photo/ Photo by Ricardo Carrasco III

More than a million Americans undergo knee and hip replacements each year. It’s a last resort treatment for pain and mobility issues associated with osteoarthritis, a progressive disease caused by degeneration of the protective layer of cartilage that stops our bones grinding together when we sit, stand, write, or move around.

But what if doctors could intervene and repair damaged cartilage before surgery is needed?

For the first time, researchers at the Keck School of Medicine of USC have used a stem cell-based bio-implant to repair cartilage and delay joint degeneration in a large animal model. The work will now advance into humans with support from a $6 million grant from the California Institute of Regenerative Medicine (CIRM).

The research, recently published in npj Regenerative Medicine, was led by two researchers at the Keck School of Medicine of USC – Denis Evseenko, MD, PhD, associate professor of orthopaedic surgery, director of the skeletal regeneration program, and vice chair for research of orthopaedic surgery; and Frank Petrigliano, MD, associate professor of clinical orthopaedic surgery and chief of the USC Epstein Family Center for Sports Medicine.

Osteoarthritis occurs when the protective cartilage that coats the ends of the bones breaks down over time, resulting in bone-on-bone friction. The disorder, which is often painful, can affect any joint, but most commonly affects those in our knees, hips, hands and spine. 

To prevent the development of arthritis and alleviate the need for invasive joint replacement surgeries, the USC researchers are intervening earlier in the disease.

“In some patients joint degeneration starts with posttraumatic focal lesions, which are lesions in the articular (joint) cartilage ranging from 1 to 8 cm² in diameter,” Evseenko said. “Since these can be detected by imaging techniques such as MRI, this opens up the possibility of early intervention therapies that limit the progression of these lesions so we can avoid the need for total joint replacement.”

That joint preservation technology developed at USC is a therapeutic bio-implant, called Plurocart, composed of a scaffold membrane seeded with stem cell-derived chondrocytes—the cells responsible for producing and maintaining healthy articular cartilage tissue. Building on previous research to develop and characterize the implant, the current study involved implantation of the Plurocart membrane into a pig model of osteoarthritis. The study resulted in the long-term repair of articular cartilage defects.

“This is the first time an orthopaedic implant composed of a living cell type was able to fully integrate in the damaged articular cartilage tissue and survive in vivo for up to six months,” Evseenko said. “Previous studies have not been able to show survival of an implant for such a long time.”

Evseenko said molecular characterization studies showed the bio-implant mimicked natural articular cartilage, with more than 95 percent of implanted cells being identified as articular chondrocytes. The cartilage tissue generated was also biomechanically functional—both strong enough to withstand compression and elastic enough to accommodate movement without breaking.

With support from the $6 million translational grant from CIRM, the researchers are using this technology to manufacture the first 64 Plurocart implants to be tested in humans.

“Many of the current options for cartilage injury are expensive, involve complex logistical planning, and often result in incomplete regeneration,” said Petrigliano. “Plurocart represents a practical, inexpensive, one-stage therapy that may be more effective in restoring damaged cartilage and improve the outcome of such procedures.”

New research presented this week at ACR Convergence, the American College of Rheumatology’s annual meeting, found that a virtual exercise program can be safe for people with musculoskeletal conditions, improved their health outcomes, and helped them feel more socially connected, an important benefit during the pandemic when many people have chosen to avoid in-person exercise classes (Abstract #1451). 

Osteoarthritis (OA) is the most common musculoskeletal condition, that causes pain, limited mobility and loss of physical function, which can affect an individual’s quality of life. OA often affects middle aged to older individuals. It is commonly referred to as “wear and tear” of the joints, but we now know that OA is a disease of the entire joint, involving the cartilage, joint lining, ligaments, and bone. OA development and progression can be affected by genetics, mechanical stress, body weight, diet, and physical activity. About 26% of U.S. adults are physically inactive, and this is more common among people 65 and older.

Nearly 75% of seniors have a musculoskeletal condition, and when coupled with physical inactivity, they are more likely to have poor health outcomes, such as lower pain tolerance, weak muscles and stiff joints. The COVID-19 pandemic added another wrinkle: older adults who stayed home to avoid exposure to the coronavirus may have felt more socially isolated and less likely to get the exercise they need at local gyms or classes.

To reach these older adults, Hospital for Special Surgery (HSS) switched their Pilates, yoga and tai chi exercise programs from onsite to the virtual platform Zoom in March 2020. This study measured the health outcomes and social connectedness of older adults who participated. “The pandemic disrupted many aspects of daily living, such as engaging in physical activity and interacting with friends and family. Unfortunately, older adults were the most vulnerable to greater health risks during this period, leading to potential worsening of musculoskeletal conditions and emotional distress,” says Titilayo Ologhobo, MPH, Director, Outcomes and Data Analytics at HSS and the study’s author. “Healthcare delivery is constantly changing, but considering the impacts of the lockdown, there was a need to quickly adapt to virtual programming, especially for vulnerable older adults. We need to know if virtual exercise classes are effective for older adults, because it provides continued access to these services, keeps them physically active from the comfort of their homes, and reduces isolation.” 

All classes were 60 minutes long and low intensity. Participants were able to talk and socialize before the guided exercises began. The researchers evaluated the programs’ effectiveness based on pre- and post-course online surveys. They assessed the socio-demographics of the participants, as well as self-reported health outcomes like pain intensity, pain interference with daily life, physical function, stiffness, fatigue, physical activity, and self-efficacy. The virtual exercise programs reached 6,779 people. Out of 355 people assessed, there were 161 who self-reported a musculoskeletal condition, mostly female, 60 or older, and white.

Overall, these participants reported a 5% decrease in pain intensity, a 7% decrease in pain interference in their walking ability, an 8% decrease in fatigue, and a 5% decrease in joint stiffness with every six-week virtual exercise session. People who participated in online exercise courses more frequently had improved pain, fatigue, stiffness and improvement in their ability to carry out their activities of daily living. Thirty-three people who participated in virtual exercise classes at least twice a week reported an 11% decrease in pain intensity, a 12% decrease in stiffness, a 9% decrease in fatigue and decreased pain interference with all aspects of daily living, including general activity levels, mood, walking ability, normal work, relations with others, sleep and enjoyment of life with every six-week virtual session. 

“Amid the uncertainties caused by the pandemic, shifting to virtual programming provided older adults with musculoskeletal conditions continued access to effective community programs and reduced the negative impact of isolation,” says Ms. Ologhobo. “Implementation of virtual online exercise programs can be successful when assessing the needs of your target audience, considering potential barriers to program participation, and tailoring virtual programs to meet patients’ specific needs.”

Get to know the science behind what causes the stiff, creaky joints of the most common forms of arthritis and what you can do to prevent it. — The bad backs, elbow pain, and creaky knees so common in older people often aren’t just “old age.” In fact, the source of this stiffness plagues many young people as well. The culprit is arthritis: a condition that affects over 90 million people in the U.S. alone. What makes arthritis so pervasive, and why haven’t we found a cure for it? Kaitlyn Sadtler and Heather J. Faust investigate. Lesson by Kaitlyn Sadtler and Heather J. Faust, directed by CUB Animation.