{"title":"Capillary Force-Driven Capture of Magnetic Nanoparticles in Calcium Phosphate Hollow-Tube Whisker Scaffolds for Osteonecrosis of the Femoral Head","authors":"Yi Zhou, Cong Feng, Xiaolong Yang, Jiang Yu, Xiangfeng Li, Weili Fu, Xiangdong Zhu, Jian Li, Xingdong Zhang","doi":"10.1021/acsnano.5c02874","DOIUrl":null,"url":null,"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/Fe<sub>3</sub>O<sub>4</sub>) 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 Fe<sub>3</sub>O<sub>4</sub> nanoparticles (NPs), achieving uniform and efficient encapsulation. HBCP/Fe<sub>3</sub>O<sub>4</sub> exhibited excellent magnetic responsiveness and significant biological effects under static magnetic field (SMF) stimulation. <i>In vitro</i>, HBCP/Fe<sub>3</sub>O<sub>4</sub> 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<sub>3</sub>O<sub>4</sub> 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<sup>2+</sup> influx, which activated BMP-2/Smad signaling and upregulated key osteogenic markers. <i>In vivo</i>, the implantation of HBCP/Fe<sub>3</sub>O<sub>4</sub> 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.","PeriodicalId":21,"journal":{"name":"ACS Nano","volume":"1 1","pages":""},"PeriodicalIF":15.8000,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"ACS Nano","FirstCategoryId":"88","ListUrlMain":"https://doi.org/10.1021/acsnano.5c02874","RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}
引用次数: 0
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 in situ 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. In vitro, 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. In vivo, the implantation of HBCP/Fe3O4 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.
期刊介绍:
ACS Nano, published monthly, serves as an international forum for comprehensive articles on nanoscience and nanotechnology research at the intersections of chemistry, biology, materials science, physics, and engineering. The journal fosters communication among scientists in these communities, facilitating collaboration, new research opportunities, and advancements through discoveries. ACS Nano covers synthesis, assembly, characterization, theory, and simulation of nanostructures, nanobiotechnology, nanofabrication, methods and tools for nanoscience and nanotechnology, and self- and directed-assembly. Alongside original research articles, it offers thorough reviews, perspectives on cutting-edge research, and discussions envisioning the future of nanoscience and nanotechnology.