Magnesium Enhances Osteogenesis of BMSCs by Tuning Osteoimmunomodulation

In the process of bone tissue engineering, the osteoimmunomodulatory property of biomaterials is very important for osteogenic differentiation of stem cells, which determines the outcome of bone regeneration. Magnesium (Mg) is a biodegradable, biocompatible metal that has osteoconductive properties and has been regarded as a promising bone biomaterial. However, the high degradation rate of Mg leads to excessive inflammation, thereby restricting its application in bone tissue engineering. Importantly, different coatings or magnesium alloys have been utilized to lower the rate of degradation. In fact, a prior study proved that β-TCP coating of Mg scaffolds can modulate the osteoimmunomodulatory properties of Mg-based biomaterials and create a favorable immune microenvironment for osteogenesis. However, the osteoimmunomodulatory properties of Mg ions themselves have not been explored yet. In this study, the osteoimmunomodulatory properties of Mg ions with involvement of macrophages and bone marrow stem cells (BMSCs) were systematically investigated. Microscale Mg ions (100 mg/L) were found to possess osteoimmunomodulatory properties that favor bone formation. Specifically, microscale Mg ions induced M2 phenotype changes of macrophages and the release of anti-inflammatory cytokines by inhibiting the TLR-NF-κB signaling pathway. Microscale Mg ions also stimulated the expression of osteoinductive molecules in macrophages while Mg ions/macrophage-conditioned medium promoted osteogenesis of BMSCs through the BMP/SMAD signaling pathway. These findings indicate that manipulating Mg ion concentration can endow the Mg biomaterial with favorable osteoimmunomodulatory properties, thereby providing fundamental evidence for improving and modifying the effect of Mg-based bone biomaterials.