A bioengineered molecule designed to bind together key components found in the fluid that surrounds joint areas may improve lubrication and minimize friction. This could potentially slow the degeneration of cartilage tissue that occurs in knee osteoarthritis, according to a study conducted in rats and funded in part by the NIH’s National Institute of Arthritis and Musculoskeletal and Skin Diseases. The study was published in Nature Materials.
The synovial fluid that bathes our joints is composed of several types of lubricants, including hyaluronic acid (HA) and lubricin. In healthy joints, this fluid ensures that tissues move together smoothly and without friction. In joints affected by osteoarthritis, insufficient lubrication caused by low levels of HA leads to cartilage degeneration and pain.
In some studies, HA has been injected directly into joints to provide better lubrication, but the results of these studies have been mixed. In some cases, the injected HA appears to quickly dissipate away from the joint, and it fails to reach or stay in the target areas most in need of lubrication.
To increase the effectiveness of injecting HA, Jennifer Elisseeff, Ph.D., of Johns Hopkins University, and her team developed a compound designed to bind HA with cartilage tissue in joints. The compound mimics the function of lubricin, which is typically found on the surface of healthy cartilage.
“The goal was to find a way to deliver HA to the needed areas and anchor it in place, ensuring the lubrication gets to where it is needed most,” said Dr. Elisseeff.
The compound-enhanced HA was first injected into normal rat knees. Imaging studies revealed that HA was retained for a significantly longer period of time in these joints compared to control joints that were injected with HA without the compound—up to 12 times longer. The researchers then tested the compound in normal and osteoarthritic cartilage samples. Results suggested that the compound-enhanced HA improved lubrication of rough osteoarthritic cartilage surfaces more so than normal tissue. Further experiments found that the bioengineered compound functioned well both in the presence and absence of lubricin.
“In joints that lack the key lubricants, our binding compound can help concentrate what limited HA is available at the tissue surface, as well as significantly improve lubrication,” said Elisseeff.
Further studies showed that the technology also holds promise for improving eye drop solutions designed to treat dry eye conditions, or encourage healing after ophthalmic trauma or surgery. Future clinical studies will be needed to determine the safety and effectiveness in human patients.
The study was supported by NIAMS (grant number R01AR054005) and by a Ruth L. Kirschstein National Research Service Award from the NIH’s National Institute on Aging (F31AG328232). The U.S. Department of Defense, the Arthritis Foundation, the Wallace H. Coulter Foundation, and the Ort Philanthropic Fund also provided support.
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Singh A, Corvelli M, Unterman SA, Wepasknick KA, McDonnell P, Elisseeff JH. Enhanced lubrication on tissue and biomaterial surfaces through peptide-mediated binding of hyaluronic acid. Nature Materials. 2014 Oct; 13(10):988-995. PMID: 25087069.
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