Tetrahedral Framework Nucleic Acids Promote Senile Osteoporotic Fracture Repair by Enhancing Osteogenesis and Angiogenesis of Callus

Senile osteoporotic fracture has aroused increasing attention due to high morbidity and mortality. However, to date, there is no effective therapeutic approach available. Senile osteoporosis is characterized by impaired osteogenesis and angiogenesis, osteoporotic fracture repair could also be promoted by enhancing osteogenesis and angiogenesis. Tetrahedral framework nucleic acids (tFNAs) are a multifunctional nanomaterial that have recently been extensively used in biomedical fields, which could enhance osteogenesis and angiogenesis in vitro. Therefore, we applied tFNAs to intact and femoral fractural senile osteoporotic mice, respectively, to evaluate the effects of tFNAs on senile osteoporosis and osteoporotic fracture repair regarding the osteogenesis and angiogenesis of the callus at the early healing stages and to initially explore the potential mechanism. The outcomes showed that tFNAs had no significant effects on the osteogenesis and angiogenesis of the femur and mandible in intact senile osteoporotic mice within 3 weeks after tFNA treatment, while tFNAs could promote osteogenesis and angiogenesis of callus in osteoporotic fracture repair, which may be regulated by a FoxO1-related SIRT1 pathway. In conclusion, tFNAs could promote senile osteoporotic fracture repair by enhancing osteogenesis and angiogenesis, offering a new strategy for the treatment of senile osteoporotic fracture.