Reduced graphene oxide loaded with tetrahedral framework nucleic acids for combating orthodontically induced root resorption

Root resorption occurs outside the root or within the root canal. Regardless of its region, root resorption is irreversible and in severe cases, may even cause tooth loss. Clinically, the external surface root resorption is usually a side effect of orthodontic tooth movement. However, it is frustrating to note that there are almost no effective treatment strategies for orthodontically induced root resorption (OIRR) due to the complexity and ambiguity of etiology. In the current study, we successfully fabricated a delivery complex, reduced graphene oxide nanosheet loading with tetrahedral framework nucleic acids (tFNAs-rGO) through self-assembly. No significant cytotoxicity or organ-toxicity of the tFNAs-rGO complex was observed in cell counting kit-8 assay (CCK-8) and hematoxylin-eosin (HE) staining. Histological staining such as tartrate-resistant acid phosphatase (TRAP) staining and Micro-CT three-dimensional reconstruction were employed to explore the dynamic changes of root and peri-root tissues in OIRR mice. In vitro, we developed an induction microenvironment to testify the effects of the tFNAs-rGO delivery complex on periodontal ligament cells (PDLCs) and macrophages by quantitative RT-PCR, western blot, and immunofluorescence staining. The data showed the reduced the region of root resorption and downregulated osteoclastic activity in OIRR by the tFNAs-rGO complex treatment. Furthermore, our study demonstrated that the tFNAs-rGO delivery complex enhanced osteogenic differentiation of PDLCs and facilitated M2-phenotype polarization of macrophages to ameliorate OIRR. Collectively, the insight into the nanoscale dual-functional tFNAs-rGO delivery complex regulating the cell populations of PDLCs and macrophages in the root resorption remodeling proposes a promising therapeutic strategy for orthodontically induced root resorption.