The periodontal ligament is a fibrous joint that connects the tooth to the surrounding bone in the jaw. As a tissue, it is both highly regenerative and responsive to the load placed on it during biting and chewing. At the same time, the periodontal ligament is vulnerable to corrosive bacterial infection that can cause loose and lost teeth.
This breakdown of the periodontal ligament is one form of periodontal disease. While it happens mostly in old age, it can occur in young people, too, and is particularly associated with socioeconomic populations that have poorer access to dental services.
Naturally, periodontists and other dental care providers are interested in ways to promote regeneration of the periodontal ligament. To do that, they need to understand what the cells that form these tissues experience and how they work together to turn on the repair process when things go wrong.
To-date, much of this research has been limited to two-dimensional models. Now, a team led by UW researchers from the Institute for Stem Cell and Regenerative Medicine (ISCRM) and the School of Dentistry have used a sophisticated 3D modeling system, originally developed to measure the force of beating heart cells, to reveal new insights about the cellular dynamics at work in the periodontal ligament. Their findings appear in The Journal of Dental Research.
The senior author of the paper is Nate Sniadecki PhD, a Professor of Mechanical Engineering and an Interim Co-Director of ISCRM. Tracy Popowics PhD, a professor of Oral Health Sciences, collaborated with the Sniadecki Lab on the research. The first author is Priti Mulimani, MDS, PhD. Dr. Mulimani, an orthodontist by training, contributed to the effort as a postdoctoral researcher at the University of Washington.
The collaboration was born when Popowics learned about an innovative tool developed in the Sniadecki Lab. In that system, which was created to measure the force produced by engineered cardiac tissues, cell-laden scaffolds are arrayed between two posts – one rigid, one flexible. When the cells within the engineered tissues contract, the force is measured by magnetic sensors.
“When I found out Nate was studying the mechanobiology of cells and tissues, I was really excited,” says Popowics, who spent time researching in the Sniadecki Lab in between teaching basic sciences to first year dental students. “It was clear to me that his engineered heart tissue system could be adapted to study the periodontal ligament.”
In the meantime, Mulimani enrolled in the School of Dentistry’s PhD program and began working with Popowics, who recommended she do a rotation in the Sniadecki Lab, where she focused on cell culture while being co-mentored by Sniadecki and Popowics. She is now a postdoctoral researcher at the University of Illinois Chicago.
The triumvirate behind the paper formed around a shared curiosity about the cellular interactions that underpin tissue regeneration in the periodontal ligament. In the Sniadecki Lab, Mulimani engineered a 3D environment designed to mimic the natural habitat that cells would call home in an actual ligament. Using magnets, she applied force to tug and stretch the suspended tissues. Under these conditions, the researchers were able to observe the remodeling process and track which genes were being activated.
“I think the most important outcome of the study is the validation of a 3D modeling method that recreates the physiological complexity of the periodontal ligament,” says Popowics. “This gives the field a new platform for testing periodontal therapeutics and for learning to promote better regeneration of these tissues, which will help improve patient care.”
An example of force being applied in a clinical context is orthodontic braces, which very slowly and carefully move teeth. Insights about what is happening in the periodontal ligament during this controlled repositioning could make life with braces more bearable and even eliminate the need for retainers.
“It was exciting to get all the data we gleaned from the gene sequencing,” Sniadecki adds. “It’s a treasure chest of information. I was also pleased from a biomechanical perspective that the elongation and elasticity of the tissues matched what we expected to see.”