A Biodegradable Magnesium Alloy Promotes Subperiosteal Osteogenesis Via Interleukin-10-Dependent Macrophage Immunomodulation

Abstract

In situ bone regeneration and vertical bone augmentation have been huge problems in clinical, always imposing a significant economic burden and causing patient suffering. Herein, MgZnYNd magnesium alloy rod implantation in mice femur results in substantial subperiosteal new bone formation, with osteoimmunomodulation playing a pivotal role. Abundant macrophages are 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) blockage effectively diminish the MgZnYNd alloy-induced subperiosteal osteogenesis. Mechanistically, the degradation products of MgZnYNd alloy promote M2 macrophage polarization and the secretion of anti-inflammatory cytokine IL-10, which enhances periosteum-derived stem cells (PDSCs) osteogenesis through the JAK1-STAT3 pathway. An anti-IL-10 neutralizing antibody or STAT3 inhibitor significantly inhibits M2 macrophage-mediated osteogenic differentiation of PDSCs. Transcriptomic and proteomics reveal that periostin is the core regulator of PDSCs osteogenesis differentiation. Furthermore, a novel clinical translation application of Mg-induced subperiosteal osteogenesis is 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.