Noting that synthetic materials and other approaches have proved ineffective, researchers at the University of California Irvine (UCI) are developing biological temporomandibular joint (TMJ) discs that will be suitable for implantation in human beings.
“The TMJ is central to chewing, talking, and so many other daily activities. So when this crucial joint is impaired, there are significant negative effects on quality of life,” said Kyriacos A. Athanasiou, PhD, PhM, MS, distinguished professor of biomedical engineering.
“The problem may start with slight pain and clicking but get progressively worse to the point where it’s not just impacting the jaw but the entire body,” Athanasiou said.
According to the researchers, one in four people are impacted by TMJ defects, and many sufferers resort to palliative measures to cope. TMJ disorders can be the result of sudden injuries or wear and tear over time as the cartilage disc between the mandible and temporal bone is subject to thinning or perforation.
The condition usually affects patients between the ages of 20 and 50. Premenopausal women are eight times more likely to experience these problems than men, which Athanasiou calls the TMJ gender paradox.
Treatments include physical therapy, splints and adjustments, corticosteroid injections, and pain medication. Only about 5% of sufferers are candidates for surgical interventions.
“It has to do with the proximity of the TMJ to the brain,” Athanasiou said. “Back in the 1980s, many patients, primarily women, came forward with issues they had with the TMJ. The solution at the time was to insert a spacer between the two bones articulated in the jaw.”
The spacer was made of Teflon, a material approved by the Food and Drug Administration (FDA).
“It turns out that Teflon was an absolute catastrophe for all of those women,” Athanasiou said. “Because of the large mechanical forces generated in the jaw, the Teflon broke up into pieces, and because of the proximity of the TMJ to the brain, those pieces somehow found their way into the brain.”
These negative outcomes, which the researchers said set back therapies for temporomandibular disorders for decades, prompted their investigations into new approaches that eschew synthetic materials entirely.
“The end product that we aspire to use for treating afflictions of TMJ discs is a tissue-engineered product that’s fully alive, biological, and mechanically comparable to the real thing,” said Ryan Donahue, a UCI graduate student researcher in biomedical engineering. “So even if it breaks down, it will be like any other biological component, without having pieces of foreign material entering the brain.”
In previous research, Athanasiou and his team successfully took cells from the rib cartilage of a Yucatan miniature pig, grew them in their laboratory, and implanted the tissue-engineered construct into a separate animal.
While some researchers may place bioengineered cells in some other part of an animal’s body, such as a mouse’s back, Athanasiou said a key aspect of his group’s work is to put the new disc in the exact place as the old one so it will be subject to all the normal stresses of the joint.
“In eight weeks, we saw complete functionality of the TMJ disc, whereas the ones we left untreated deteriorated completely, developing full osteoarthritis in the joint,” said Jerry Hu, PhD, principal development engineer in biomedical engineering. “So we were able to show that by using our tissue-engineering approach in a large-animal model, we could achieve exceptional healing.”
Athanasiou said his team’s goal now is to conduct trials in more large-animal models to determine if their solution will ultimately work in humans. A major hurdle will be gaining regulatory approval from the FDA, but Athanasiou recently received encouraging signals from the agency.
“The FDA has asked if we could help them figure out how to go about developing processes for bringing TMJ products to the market,” Athanasiou said. “We would be delighted to help create that pathway.”
The study, “Remaining Hurdles for Tissue-Engineering the Temporomandibular Joint Disc,” was published by Trends in Molecular Medicine.