Sore Knees? Solving meniscus micro-structure could improve treatments.
Knee injuries are among the top five reasons people visit an orthopedic surgeon for treatments, which include 719,000 total knee replacements performed annually in the United States. Now, new research reveals underlying biomechanics that may be involved in meniscus fibrocartilage function as well as dysfunction and could guide novel treatments for some of the most debilitating and costly orthopedic problems in the United States, including meniscus tears and age-related joint degeneration.
The knee meniscus is a piece of cartilage between the leg bones that cushions and stabilizes the joint, protecting the bones from wear and tear. In studies of samples from cows and humans, bioengineers funded by the National Institute of Biomedical Imaging and Bioengineering identified small patches of non-fibrous "islands" known as microdomains in the knee fibrocartilage that makes up the meniscus. Samples from older animals and humans consistently had larger microdomains. The discovery opens the way for a more detailed examination of fibrocartilage microstructure and how changes at the cellular and molecular levels contribute to orthopedic health and disease.
"This is impressive and important work," said Rosemarie Hunziker, Ph.D., director of the NIBIB Program in Tissue Engineering and Regenerative Medicine, "both in the fundamental discovery and the fact that they rapidly built a model to study it."
The discovery by researchers at the University of Delaware and the University of Pennsylvania and subsequent development of a bioengineered model of the tissue are reported in the Jan. 4 issue of Nature Materials.
The group examined cow knee tissue samples spanning from fetal development through adulthood. The microdomains, interspersed within the fibrocartilage of the meniscus, were present at the fetal stage in cow samples and grew larger in size, but not number, as the age of the animal increased. Studies of human samples revealed the same correlation between advanced age and increased size of microdomains.
In addition to the increase in microdomains with age, human donors with higher body mass index also had increases in the size of the microdomains. "Taken together, these observations suggested that increased microdomain size might be an adaptive response to handle increased mechanical load accumulating over time or increased pressure on the meniscus in heavier individuals," explained Dawn Elliott, Ph.D., chair of the University of Delaware's Department of Biomedical Engineering and senior co-author of the study. "An important question we immediately had was whether such an adaptation could be pushed to the point where it could also lead to impaired function of knee fibrocartilage."