Nanoparticles May Help Repair Injured Joints

By Pat Anson, Editor

Injecting an injured joint with nanoparticles – tiny, ultrafine particles so small they are invisible to the naked eye – controls inflammation and may help prevent the development of osteoarthritis, according to a new study.

Researchers at the Washington University School of Medicine in St. Louis found that injecting nanoparticles into the injured joints of laboratory mice reduces inflammation and the destruction of cartilage.

The nanoparticles used are more than 10 times smaller than a red blood cell, which helps them penetrate deeply into tissues.  The nanoparticles carry a peptide derived from a natural protein called melittin that has been modified to enable it to bind to a molecule and interfere with inflammation.

“The nanoparticles are injected directly into the joint, and due to their size, they easily penetrate into the cartilage to enter the injured cells,” said Samuel Wickline, MD, a professor of Biomedical Sciences at Washington University.

“Previously, we’ve delivered nanoparticles through the bloodstream and shown that they inhibit inflammation in a model of rheumatoid arthritis. In this study, they were injected locally into the joint and given a chance to penetrate into the injured cartilage.”

The nanoparticles were injected into the mice soon after an injury to prevent the inflammation and cartilage breakdown that can lead to osteoarthritis.

INFLAMMATORY PROTEIN (GREEN) IN CARTILAGE CELLS. IMAGE COURTESY of UNIVERSITY OF WASHINGTON SCHOOL OF MEDICINE

INFLAMMATORY PROTEIN (GREEN) IN CARTILAGE CELLS. IMAGE COURTESY of UNIVERSITY OF WASHINGTON SCHOOL OF MEDICINE

Whether such a strategy will work in humans years after an injury -- when osteoarthritis is established and there is severe cartilage loss -- still needs to be studied. But the findings suggest that the nanoparticles, if given soon after joint injuries occur, could help maintain cartilage and prevent the progression to osteoarthritis.

“I see a lot of patients with osteoarthritis, and there’s really no treatment,” said senior author Christine Pham, MD, an associate professor of medicine. “We try to treat their symptoms, but even when we inject steroids into an arthritic joint, the drug only remains for up to a few hours, and then it’s cleared. These nanoparticles remain in the joint longer and help prevent cartilage degeneration.”

Osteoarthritis (OA) is a joint disorder that leads to thinning of cartilage and progressive joint damage. Nearly 40 percent of Americans over the age of 45 have some degree of knee OA, and those numbers are expected to grow as the population ages. Frequently, an osteoarthritis patient has suffered an earlier injury — a torn meniscus or ACL injury in the knee. The body naturally responds to joint injuries with inflammation.

“The inflammatory molecule that we’re targeting not only causes problems after an injury, but it’s also responsible for a great deal of inflammation in advanced cases of osteoarthritis,” said Linda Sandell, PhD, a professor of Orthopaedic Surgery and director of Washington University’s Center for Musculoskeletal Research.

“So we think these nanoparticles may be helpful in patients who already have arthritis, and we’re working to develop experiments to test that idea.”

The study findings are published in the Proceedings of the National Academy of Sciences. The study was funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases; the National Heart, Lung, and Blood Institute; and the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health.