Osteoarthritis is said to affect more than 20 million people in the United States and a major reason it impacts so many is that there is no known cure. It can be treated in an effort to alleviate the painful symptoms but there is no method that can effectively reverse the breakdown of cartilage associated with the disease. One new development, however, could start to change that.
Engineers at MIT have designed a new material that could allow them to administer drugs directly to the damaged cartilage. And if proven effective for people it’s expected that this advancement could heal damaged tissue.
"This is a way to get directly to the cells that are experiencing the damage, and introduce different kinds of therapeutics that might change their behavior," says Paula Hammond, head of MIT's Department of Chemical Engineering, a member of MIT's Koch Institute for Integrative Cancer Research, and the senior author of the study.
Researchers examined the effects of an experimental drug called insulin-like growth factor 1 (IGF-1) on rats by injecting it with their specific material. In their studies, the treatment prevented cartilage breakdown in the rats more effectively that administering the drug directly to the joints. And while previous studies with IGF-1 have shown the drug to be effective in regenerating cartilage in animals, many osteoarthritis drugs in the past have performed well in animal studies but not so well in clinical studies. The MIT team believes this is simply because such drugs were cleared from the joints before penetrating deep into the layer of chondrocytes — a cell that has secreted the matrix of cartilage and becomes embedded in it — that they targeted.
"We found an optimal charge range so that the material can both bind the tissue and unbind for further diffusion, and not be so strong that it just gets stuck at the surface," Brett Geiger, an MIT graduate student and the lead author of the paper says, explaining that the sphere-shaped molecule they’ve designed contains many branched structures called dendrimers that branch from a central core, allowing the molecule positive charge to bind with negatively charged cartilage. Once the particles reach the chondrocytes, IGF-1 binds to receptors on the cell surface and stimulate them to start producing proteoglycans, the building blocks of cartilage and other connective tissues.
In their studies, researchers found their method of injecting the particles into the knee joints of rats had a half-life of approximately four days, 10 times longer than when IGF-1 is injected on its own. If the same proves to be true in clinical trials for humans, patients could get monthly or bi-monthly injections.
"That is a very hard thing to do. Drugs typically will get cleared before they are able to move through much of the cartilage," Geiger says. "When you start to think about translating this technology from studies in rats to larger animals and someday humans, the ability of this technology to succeed depends on its ability to work in thicker cartilage."