A biodegradable magnesium alloy promotes subperiosteal osteogenesis via interleukin-10-dependent macrophage immunomodulation

In situ bone regeneration and vertical bone augmentation have been huge problems in clinical practice, always imposing a significant economic burden and causing patient suffering. Herein, MgZnYNd magnesium alloy rod implantation in mouse femur resulted in substantial subperiosteal new bone formation, with osteoimmunomodulation playing a pivotal role. Abundant macrophages were attracted to the subperiosteal new bone region and proved to be the most important regulation cells for bone regeneration. Periosteum stripping, macrophage depletion, and interleukin-10 (IL-10) blockade effectively diminished the MgZnYNd alloy-induced subperiosteal osteogenesis. Mechanistically, the degradation products of MgZnYNd alloy promoted M2 macrophage polarization and the secretion of anti-inflammatory cytokine IL-10, which enhanced periosteum-derived stem cells (PDSCs) osteogenesis through the JAK1-STAT3 pathway. An anti-IL-10 neutralizing antibody or STAT3 inhibitor significantly inhibited M2 macrophage-mediated osteogenic differentiation of PDSCs. Transcriptomics and proteomics revealed that periostin is the core regulator of PDSCs osteogenic differentiation. Furthermore, a novel clinical translation application of Mg-induced subperiosteal osteogenesis was developed, demonstrating its ability to preserve the height and width of the alveolar crest in rats and rabbits following tooth extraction. Collectively, these findings unveil a previously undefined role for Mg alloy-induced subperiosteal osteogenesis via macrophage-mediated osteoimmunomodulation, suggesting the therapeutic potential of magnesium alloy in bone regeneration and bone augmentation.