A Multifunctional miRNA Delivery System Based on Tetrahedral Framework Nucleic Acids for Regulating Inflammatory Periodontal Ligament Stem Cells and Attenuating Periodontitis Bone Loss

Periodontitis is a chronic inflammatory disease that leads to periodontal tissue damage and tooth loss. Therefore, controlling inflammatory bone loss and promoting osteogenesis is a crucial challenge clinically. MicroRNA (miRNA) based gene therapy has shown substantial prospects in recent years, but its application has been limited due to structural instability and easy degradation by enzymes. Research has shown that miRNA-200c is regarded as a key miRNA by regulating multiple signaling pathways during the process of bone resorption. Tetrahedral framework nucleic acid (tFNA) can be considered an ideal carrier of miRNA due to its good tissue permeability, cell uptake efficiency, and biocompatibility. This study developed a tFNA system carrying miR-200c, named T-200c, to exert various biological effects in human periodontal ligament stem cells (PDLSCs). The activation of the NF-κB pathway is diminished, whereas the Akt/β-catenin pathway is enhanced, resulting in a notable decrease in the release of diverse inflammatory mediators and cellular reactive oxygen species. This modulation fosters cell proliferation and osteogenic differentiation, thereby rejuvenating the functionality of PDLSCs. These changes offer a viable alternative for the treatment of periodontitis and the regeneration of periodontal tissues.