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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)\u2010treated BMSC model in vitro and a methylprednisolone (MPS)\u2010induced 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\u2010dose glucocorticoids (GCs) through the hedgehog and Akt\/Bcl\u20102 pathways, contributing to the prevention of GC\u2010induced ONFH in rats. Thus, TPC is a promising drug for the treatment of ONFH and other osteogenesis\u2010related diseases.<\/jats:p>","DOI":"10.1002\/smll.202302326","type":"journal-article","created":{"date-parts":[[2023,6,15]],"date-time":"2023-06-15T04:02:05Z","timestamp":1686801725000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":70,"title":["Effects of Puerarin\u2010Loaded Tetrahedral Framework Nucleic Acids on Osteonecrosis of the Femoral Head"],"prefix":"10.1002","volume":"19","author":[{"given":"Yuxuan","family":"Zhao","sequence":"first","affiliation":[{"name":"State Key Laboratory of Oral Diseases National Clinical Research Center for Oral Diseases West China Hospital of Stomatology Sichuan University Chengdu 610041 P. R. 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