Engineering and Dentistry Researchers Harness the Mouth’s Own Cellular Structures to Regenerate Oral Tissues in NIH-Funded Project

Barbara Boyan, Zvi Schwartz and Zhao Lin
Zhao Lin, B.D.S., Ph.D., Barbara D. Boyan, Ph.D. and Zvi Schwartz, D.M.D., Ph.D., are collaborators on an NIH-funded study to regenerate oral tissues by harvesting nanovesicles from stem cells.

By Rebecca E. Jones

VCU faculty in Engineering and Dentistry are developing a better way to regenerate oral tissues in patients suffering from gum diseases or trauma to the mouth. Principal investigator Zhao Lin, B.D.S., Ph.D., assistant professor of periodontics in the School of Dentistry, leads an interdisciplinary team working to harness the mouth’s own naturally occurring cellular structures to regenerate gum and bone tissue. The process will offer a safer, more predictable alternative to current methods of periodontal tissue augmentation. Barbara D. Boyan, Ph.D., Alice T. and William H. Goodwin Chair and dean of the VCU School of Engineering, and Zvi Schwartz, D.M.D., Ph.D., professor of biomedical engineering and associate dean for strategic operations in the School of Engineering, are consultants on the study, which has received funding from the National Institutes of Health.

“This research has grown out of a longstanding collaboration made possible by a joint investment in the development of new technologies for oral health care between the schools of Engineering and Dentistry. It takes an interdisciplinary approach to make basic research real for clinical applications. Dr. Lin is an outstanding example of the kind of faculty VCU brings to these challenging problems,” Boyan said.

Bone grafts and guided tissue regeneration are the most common methods to stimulate formation of new bone and gum tissue. Their shortcoming, Lin said, is that they often produce too little tissue and the outcome is usually not predictable. Stem cell therapy holds great promise, but the current stem cell treatment strategy is impractical for many dental practitioners because of the time and equipment required. Large doses of stem cells may also cause other concerns such as potential formation of tumors when placed in a patient. Lin’s team hopes to isolate the regenerative power of stem cell therapy — and reduce the complications and risk.

“A lot of the benefit of stem cell therapies comes from byproducts the stem cells produce,” Lin said. “Specific nanovesicles carry the benefits of the stem cell. We want to harvest those nanovesicles from the stem cell and use them to regenerate tissue.”  

The nanovesicles Lin’s team is targeting are exosomes, which are cellular structures consisting of fluid enclosed in a lipid bilayer. They are secreted by most cell types and are naturally occurring delivery vehicles for genetic material and growth factors.  “Our preliminary studies showed that these exosomes have potent anti-inflammatory effects and can stimulate stem cell migration and proliferation,” he said. Under the NIH grant, the group will test effectiveness of exosome delivery to alleviate periodontal inflammation and promote tissue regeneration. The study will also investigate the function of microRNAs in these processes. The goal is a much more targeted treatment that yields the right amount of tissue without the risks associated with whole stem cells.

Lin worked with Boyan and Schwartz before from 2013-15, while he was a faculty member in the School of Dentistry. He was conducting postdoctoral research in Boyan’s lab through a special arrangement between the schools of Dentistry and Engineering to develop an independent research program. Lin helped support Boyan’s lab’s work to identify small RNA in matrix vesicles, which are extracellular organelles that are present during calcification in cartilage, bone and teeth and contain enzymes needed for preparing the matrix for calcification. Lin said the chance to work with Boyan and Schwartz, who are known internationally for their pioneering achievements in oral tissue engineering, was a major factor in his decision to come to VCU. “When I started my own lab in 2015 in dental school, I was inspired by the matrix vesicle story.” Lin said. “Now, with the continued support from Dr. Boyan's group, I am exploring the regenerative potential of extracellular vesicles such as exosomes in periodontal tissues.”

Other collaborators in this project also include Sinem Esra Sahingur, D.D.S., Ph.D., associate professor of periodontics in the School of Dentistry, and William V. Giannobile, D.D.S., M.S., D.M.Sc., chair of the Department of Periodontics and Oral Medicine in the University of Michigan School of Dentistry.