MIT engineers design new material that may someday help heal osteoarthritis
MIT engineers have designed a new molecule that can administer drugs deep into cartilage in an effort to help reverse or slow the tissue breakdown associated with osteoarthritis.
The disease, caused by aging or traumatic injury, affects 20 to 30 million people in the United States, sometimes bringing severe joint pain and limiting mobility.
Drug treatments available today can only alleviate the pain, not eliminate the source of it, researchers said. They said they hoped their discovery would one day lead to better treatment.
Cartilage, a smooth connective tissue that protects joints, does not have any blood vessels, making it difficult for drugs to travel to the deeper layers of chondrocytes, the cells that produce and maintain cartilage.
MIT’s new molecule can penetrate deep into the tissue, delivering drugs that can potentially help the chondrocytes heal cartilage.
“This work was less about coming up with a brand-new therapy for osteoarthritis, and more about solving this old and very cumbersome challenge with rational molecular engineering based on deep understanding of the biology of the cartilage delivery problem,” Brett Geiger, an MIT graduate student and lead author of the study, said in an e-mail.
The paper was published in Wednesday’s issue of the journal Science Translational Medicine.
Researchers turned to a round molecule with structures branching from it called a dendrimer. Think of it as a “dynamically moving” snowflake, said Paula Hammond, head of MIT’s department of chemical engineering and senior author of the study.
The tips of the branches have positive charges that bind them to the negatively charged cartilage, researchers said. But the bonding between the molecule and cartilage can be too strong, researchers said, trapping the molecule on the cartilage’s surface. To solve the problem, Geiger said, researchers added a polymer known as PEG to the dendrimers.
The polymers swing around the tips of the branches, covering and uncovering some of the charges, enabling the molecule to briefly detach from the surface cartilage and move deeper into the tissue, researchers said.
“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,” Geiger said.
The new material could be used to deliver a drug called insulin-like growth factor 1, or IGF-1, which has been found to regenerate cartilage in animals, according to studies done on rats, researchers said. The idea was to deliver IGF-1 all the way through the cartilage.
In rats, injecting the IGF-1 as “therapeutic cargo” in tandem with the new material produced better results than injecting the IGF-1 into the joint on its own, researchers said.
Human cartilage is much thicker than that of rats, so “the ability of this technology to succeed depends on its ability to work in thicker cartilage,” Geiger said.
The technology is likely years away from testing in people, Geiger said. In the next phase of their research, the MIT team plans to test their technology in donated human cartilage from cadavers, Geiger said.