Mineralization of ytterbium-doped hydroxyapatite nanorod arrays in magnetic chitosan scaffolds improves osteogenic and angiogenic abilities for bone defect healing

Hydroxyapatite (HA) is a traditional bone repair material, but its poor osteogenic and angiogenic abilities hinder the clinical application for critical-sized bone defect healing. Herein, ytterbium-doped hydroxyapatite (YbHA) nanorod arrays in situ deposited in magnetic chitosan (CS) porous scaffolds, leading to create magnetic YbHA/CS (MYbHA/CS) nanohybrid scaffolds. We hypothesized that both magnetic SrFe12O19 nanoplates and Yb dopants in the functional scaffolds favored the osteogenesis and vascularization in bone defect regions. To prove the hypothesis, the osteogenic and angiogenic activities of MYbHA/CS scaffolds were investigated by using rat bone marrow mesenchymal stem cells (rBMSCs) and rat cranial defects as models. Fortunately, both the magnetic fields and Yb3+ ions as-derived from MYbHA/CS scaffolds remarkably up-regulated the expression of osteogenicrelated genes by activating BMP-2/Smad pathway, and simultaneously increased the expression of vascular endothelial growth factor. In vivo rat cranial defect models further revealed that the combination effects between magnetic SrFe12O19 nanoplates and Yb dopants remarkably stimulated the in-growth of blood vessels and new bones into three-dimensional channels in the nanohybrid scaffolds. Hence, the modification of SrFe12O19 nanoplates and Yb dopants in bone scaffolds is a novel and promising strategy to accelerate bone defect healing.