Chronic oral diseases can be difficult to treat because damaged tissue is trapped in a harmful cycle: inflammation generates excessive reactive oxygen species (ROS), while those molecules further intensify inflammation and tissue destruction. Now, researchers at Sichuan University and collaborating institutions have reviewed a promising nanotechnology-based strategy that could help interrupt this cycle and create better conditions for oral tissue regeneration.
The review, titled "ROS-scavenging tetrahedral framework nucleic acids: reprogramming the pathological microenvironment for oral tissue regeneration," was published in Oral Science and Homeostatic Medicine in 2026. Rather than reporting a new clinical treatment, it brings together evidence on the biological mechanisms, material designs and preclinical applications of tetrahedral framework nucleic acids (tFNAs).
ROS are not inherently harmful. At normal levels, they help cells communicate and defend against microbes. But when their production outpaces the body's antioxidant defenses, ROS can damage DNA, proteins and cell membranes. In periodontal disease, oral submucous fibrosis and some forms of jaw osteonecrosis, this imbalance can sustain inflammatory signaling, disrupt bone remodeling and impede healing.
The review highlights tFNAs as an unusual two-in-one therapeutic platform. Formed by the self-assembly of short DNA strands into nanoscale tetrahedrons, these structures can exhibit ROS-scavenging activity while also serving as carriers for molecules such as small interfering RNAs, microRNAs, antioxidants and bioactive peptides. Their programmable shape enables researchers to modify the structures for specific therapeutic tasks.
This combination matters because simply removing harmful molecules may not be enough. Functionalized tFNAs could also influence signaling networks involved in inflammation, antioxidant defense and cell survival, including NF-κB, NLRP3 and Nrf2. By addressing several parts of the destructive cycle at once, researchers hope to move beyond symptom control toward supporting tissue repair.
The authors survey experimental approaches for conditions ranging from periodontitis to bisphosphonate-related osteonecrosis of the jaw and oral mucosal injury. In some animal models, tFNA-based systems have reduced inflammatory or oxidative markers and improved measures of wound healing or bone repair. The review also describes delivery advances, including hydrogels designed to retain treatments locally and systems that respond to acidic inflammatory environments.
However, translating these findings into patient care will require more than encouraging preclinical results. Important questions remain about long-term safety, how long the nanostructures stay in tissues, how they are cleared from the body, and whether they can be produced consistently at clinical scale. The authors identify localized delivery for periodontitis as a potentially practical starting point for future development.
Looking ahead, the review calls for more detailed studies of how tFNAs behave inside living tissues, alongside disease-specific designs, reliable manufacturing and rigorous safety assessments. If these hurdles can be overcome, programmable DNA nanostructures may eventually provide a new way to treat inflammatory damage while helping oral tissues regenerate.
This work was supported by the National Natural Science Foundation of China (82501114, 82370929), the China Postdoctoral Science Foundation (GZC20241127, 2024M762233), and other funding programs.
DOI Link:
https://doi.org/10.26599/OSHM.2026.9610064
About the Authors
Yunfeng Lin is a full professor, chief physician, and doctoral supervisor at the West China School/Hospital of Stomatology, Sichuan University, China. His research focuses on nucleic acid nanomaterials and regenerative medicine, particularly the development and biomedical translation of framework nucleic acid-based therapeutics. He has published 330 SCI-indexed papers as corresponding author, with approximately 25,000 citations and an H-index of 84. He has applied for more than 160 domestic and international invention patents, of which over 70 have been granted and more than 50 transferred. He has also edited nine English-language academic books. He serves as editor-in-chief of Bone Research and executive editor-in-chief of Cell Proliferation.
