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

Abstract

Bone regeneration is complex and involves multiple cells and systems, with macrophage-mediated immune regulation being critical for the development and regulation of inflammation, angiogenesis, and osteogenesis. Biomaterials with modified physical and chemical properties (e.g., modified wettability and morphology) effectively regulate macrophage polarization. This study proposes a novel approach to macrophage-polarization induction and -metabolism regulation through selenium (Se) doping. We synthesized Se-doped mesoporous bioactive glass (Se-MBG) and demonstrated its macrophage-polarization regulation toward M2 and its enhancement of the macrophage oxidative phosphorylation metabolism. The underlying mechanism is the effective scavenging of excessive intracellular reactive oxygen species (ROS) by the Se-MBG extracts through the promotion of peroxide-scavenging enzyme glutathione peroxidase 4 expression in the macrophages; this, in turn, improves the mitochondrial function. Printed Se-MBG scaffolds were implanted into rats with critical-sized skull defects to evaluate their immunomodulatory and bone regeneration capacity in vivo. The Se-MBG scaffolds demonstrated excellent immunomodulatory function and robust bone regeneration capacity. Macrophage depletion with clodronate liposomes impaired the Se-MBG-scaffold bone regeneration effect. Se-mediated immunomodulation, which targets ROS scavenging to regulate macrophage metabolic profiles and mitochondrial function, is a promising concept for future effective biomaterials for bone regeneration and immunomodulation.

Selenomethionine-Conjugated Extracellular Vesicles for ROS-Mediated Cell Apoptosis

“…As illustrated in Figure c, the fluorescence intensity of DCF in the group of SMLEV reached 2.9 times that of the control group. Considering that the mitochondrial membrane potential (△Ψm) was sensitive to the ROS accumulation in mitochondria, , we next detected △Ψm of CT26 cells after SeM or SMLEV treatment for 24 h by using JC-1 as indicators, which typically formed aggregates in live or undamaged cells with a relatively high △Ψm while residing as monomers in the apoptotic cells with a low △Ψm. As could be seen in Figure d,e, compared to the control group, the SMLEV group showed that the lowest proportion of aggregates reached 27.7% and the highest proportion of monomers reached 71.7%.…”

Repair spinal cord injury with a versatile anti-oxidant and neural regenerative nanoplatform

“…However, excess ROS induces inflammatory cell infiltration and macrophage polarization through mitochondrial homeostasis disruption and production of pro-inflammatory factors, forming a vicious cycle of central nerve inflammation and ROS production, further aggravating inflammation and the formation of glial cell scar. In non-malignant conditions, selenium supplementation of macrophages attenuates the proinflammatory function of macrophages by switching macrophage activation from the pro-inflammatory phenotype M1 to the anti-inflammatory phenotype M2 [ 63 , 64 ]. Our results suggest that FSZ NPs exhibit the ability to regulate macrophage polarization towards the protective phenotype M2.…”