Selenium-Doped Mesoporous Bioactive Glass Regulates Macrophage Metabolism and Polarization by Scavenging ROS and Promotes Bone Regeneration In Vivo

Bone regeneration is complex and involves multiple cellsand systems,with macrophage-mediated immune regulation being critical for thedevelopment and regulation of inflammation, angiogenesis, and osteogenesis.Biomaterials with modified physical and chemical properties (e.g., modified wettability and morphology) effectively regulatemacrophage polarization. This study proposes a novel approach to macrophage-polarizationinduction and -metabolism regulation through selenium (Se) doping.We synthesized Se-doped mesoporous bioactive glass (Se-MBG) and demonstratedits macrophage-polarization regulation toward M2 and its enhancementof the macrophage oxidative phosphorylation metabolism. The underlyingmechanism is the effective scavenging of excessive intracellular reactiveoxygen species (ROS) by the Se-MBG extracts through the promotionof peroxide-scavenging enzyme glutathione peroxidase 4 expressionin the macrophages; this, in turn, improves the mitochondrial function.Printed Se-MBG scaffolds were implanted into rats with critical-sizedskull defects to evaluate their immunomodulatory and bone regenerationcapacity in vivo. The Se-MBG scaffolds demonstratedexcellent immunomodulatory function and robust bone regeneration capacity.Macrophage depletion with clodronate liposomes impaired the Se-MBG-scaffoldbone regeneration effect. Se-mediated immunomodulation, which targetsROS scavenging to regulate macrophage metabolic profiles and mitochondrialfunction, is a promising concept for future effective biomaterialsfor bone regeneration and immunomodulation.