Capillary Force-Driven Capture of Magnetic Nanoparticles in Calcium Phosphate Hollow-Tube Whisker Scaffolds for Osteonecrosis of the Femoral Head

Excessive glucocorticoid use disrupts osteogenesis and angiogenesis in the femoral head, leading to steroid-induced osteonecrosis of the femoral head (SONFH), which is a significant clinical challenge. This study introduces a magnetically responsive biphasic calcium phosphate (HBCP/Fe 3 O 4 ) scaffold featuring a nanoparticle-embedded hollow-tube whisker structure. The scaffold was fabricated through an in situ growth process to generate hollow-tube whiskers, followed by a capillary trapping technique that allowed the hollow-tube whiskers to capture Fe 3 O 4 nanoparticles (NPs), achieving uniform and efficient encapsulation. HBCP/Fe 3 O 4 exhibited excellent magnetic responsiveness and significant biological effects under static magnetic field (SMF) stimulation. In vitro, HBCP/Fe 3 O 4 under SMF promoted osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) in a glucocorticoid microenvironment, enhanced angiogenesis in human umbilical vein endothelial cells (HUVECs), and induced M2 polarization of RAW 264.7 murine macrophage cells (RAW 264.7). Furthermore, HBCP/Fe 3 O 4 under SMF stimulation orchestrated paracrine signaling from endothelial and immune cells, thereby enhancing the osteogenic differentiation of BMSCs. Mechanistically, the osteogenic differentiation of BMSCs was driven by magnetic stimulation-induced Piezo1-mediated Ca 2+ influx, which activated BMP-2/Smad signaling and upregulated key osteogenic markers. In vivo, the implantation of HBCP/Fe 3 O 4 scaffolds under SMF stimulation in a rabbit SONFH model promoted coordinated therapeutic effects, including robust bone regeneration, in situ revascularization, immunomodulation, and preservation of femoral head cartilage. Together, these findings support the clinical relevance of this magnetically responsive scaffold as a multifunctional strategy for delaying structural deterioration and facilitating comprehensive repair in SONFH.