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

Abstract

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/Fe₃O₄) scaffold featuring a nanoparticle-embedded hollow-tube whisker structure. The scaffold was fabricated through an <i>in situ</i> growth process to generate hollow-tube whiskers, followed by a capillary trapping technique that allowed the hollow-tube whiskers to capture Fe₃O₄ nanoparticles (NPs), achieving uniform and efficient encapsulation. HBCP/Fe₃O₄ exhibited excellent magnetic responsiveness and significant biological effects under static magnetic field (SMF) stimulation. <i>In vitro</i>, HBCP/Fe₃O₄ 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/Fe₃O₄ 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 Ca²⁺ influx, which activated BMP-2/Smad signaling and upregulated key osteogenic markers. <i>In vivo</i>, the implantation of HBCP/Fe₃O₄ scaffolds under SMF stimulation in a rabbit SONFH model promoted coordinated therapeutic effects, including robust bone regeneration, <i>in situ</i> 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.