Dual-target nanotherapy for vascular endothelium and bone mesenchymal stem cells halt steroid-induced osteonecrosis of the femoral head progression.

Steroid-induced osteonecrosis of the femoral head (SANFH) is a common hip joint disease that imposes a heavy economic burden on society. Patients continue to experience bone necrosis even after discontinuing glucocorticoid therapy, and the specific mechanisms require further investigation. The results of this study demonstrate that exosomes secreted by damaged vascular endothelial cells in SANFH lesions may be a crucial factor leading to abnormal adipogenic differentiation of bone marrow stromal cells (BMSCs). We also found that adipogenically differentiated BMSCs can secrete increased pro-inflammatory factors, which contribute to the maintenance of endothelial cell damage, thereby creating a vicious cycle. Due to endothelial damage and abnormal differentiation of BMSCs, insufficient bone repair occurs, leading to spontaneous disease progression. Based on our newly explored mechanism, we designed a nanomaterial, M-SiO@Icariin@EBHM, that simultaneously targets the repair of damaged vascular endothelium and re-regulation of BMSCs, and we assessed its role in delaying SANFH progression. We found that the M-SiO@Icariin@EBHM nanomaterial can target SANFH lesions when applied systemically, effectively clearing the elevated reactive oxygen species in vascular endothelial cells caused by glucocorticoids and regulating the osteogenic differentiation of BMSCs. This process breaks the vicious cycle while promoting bone repair and significantly inhibiting SANFH progression, revealing its potential as a promising treatment strategy for SANFH.