Effects of Puerarin-Loaded Tetrahedral Framework Nucleic Acids on Osteonecrosis of the Femoral Head

Osteonecrosis of the femoral head (ONFH) is recognized as a common refractory orthopedic disease that causes severe pain and poor quality of life in patients. Puerarin (Pue), a natural isoflavone glycoside, can promote osteogenesis and inhibit apoptosis of bone mesenchymal stem cells (BMSCs), demonstrating its great potential in the treatment of osteonecrosis. However, its low aqueous solubility, fast degradation in vivo, and inadequate bioavailability, limit its clinical application and therapeutic efficacy. Tetrahedral framework nucleic acids (tFNAs) are promising novel DNA nanomaterials in drug delivery. In this study, tFNAs as Pue carriers is used and synthesized a tFNA/Pue complex (TPC) that exhibited better stability, biocompatibility, and tissue utilization than free Pue. A dexamethasone (DEX)-treated BMSC model in vitro and a methylprednisolone (MPS)-induced ONFH model in vivo is also established, to explore the regulatory effects of TPC on osteogenesis and apoptosis of BMSCs. This findings showed that TPC can restore osteogenesis dysfunction and attenuated BMSC apoptosis induced by high-dose glucocorticoids (GCs) through the hedgehog and Akt/Bcl-2 pathways, contributing to the prevention of GC-induced ONFH in rats. Thus, TPC is a promising drug for the treatment of ONFH and other osteogenesis-related diseases.

Automated summary

Osteonecrosis of the femoral head (ONFH) is a common refractory orthopedic disease that causes severe pain and poor quality of life. Puerarin (Pue), a natural isoflavone glycoside, shows potential in treating ONFH by promoting osteogenesis and inhibiting apoptosis of bone mesenchymal stem cells (BMSCs). However, the limitations of Pue, such as low solubility, fast degradation, and inadequate bioavailability, hinder its clinical application. In this study, tetrahedral framework nucleic acids (tFNAs) are used as carriers for Pue, resulting in a tFNA/Pue complex (TPC) that exhibits enhanced stability, biocompatibility, and tissue utilization. In vitro and in vivo models are established to investigate the effects of TPC on osteogenesis and apoptosis of BMSCs under glucocorticoid-induced conditions. The findings demonstrate that TPC can restore osteogenesis dysfunction and attenuate BMSC apoptosis through hedgehog and Akt/Bcl-2 pathways, offering a promising treatment for GC-induced ONFH.