Activating autologous stem cells after the implantation of biomaterials is an important process to initiate bone regeneration. Although several studies have demonstrated the mechanism of biomaterial‐mediated bone regeneration, a comprehensive single‐cell level transcriptomic map revealing the influence of biomaterials on regulating the temporal and spatial expression patterns of mesenchymal stem cells (MSCs) is still lacking. Herein, the osteoimmune microenvironment is depicted around the classical collagen/nanohydroxyapatite‐based bone repair materials via combining analysis of single‐cell RNA sequencing and spatial transcriptomics. A group of functional MSCs with high expression of matrix Gla protein (Mgp) is identified, which may serve as a pioneer subpopulation involved in bone repair. Remarkably, these Mgp high‐expressing MSCs (MgphiMSCs) exhibit efficient osteogenic differentiation potential and orchestrate the osteoimmune microenvironment around implanted biomaterials, rewiring the polarization and osteoclastic differentiation of macrophages through the Mdk/Lrp1 ligand–receptor pair. The inhibition of Mdk/Lrp1 activates the pro‐inflammatory programs of macrophages and osteoclastogenesis. Meanwhile, multiple immune‐cell subsets also exhibit close crosstalk between MgphiMSCs via the secreted phosphoprotein 1 (SPP1) signaling pathway. These cellular profiles and interactions characterized in this study can broaden the understanding of the functional MSC subpopulations at the early stage of biomaterial‐mediated bone regeneration and provide the basis for materials‐designed strategies that target osteoimmune modulation.

中文翻译：

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Mgp 高表达 MSC 协调胶原/纳米羟基磷灰石介导的骨再生的骨免疫微环境

生物材料植入后激活自体干细胞是启动骨再生的重要过程。尽管多项研究已经证明了生物材料介导的骨再生机制，但仍缺乏全面的单细胞水平转录组图谱来揭示生物材料对调节间充质干细胞（MSC）时空表达模式的影响。在此，通过单细胞 RNA 测序和空间转录组学的结合分析，描绘了经典胶原/纳米羟基磷灰石基骨修复材料周围的骨免疫微环境。一组高表达基质Gla蛋白的功能性MSCs（镁合金）被鉴定出来，它可能作为参与骨修复的先驱亚群。值得注意的是，这些镁合金高表达间充质干细胞（镁合金你好MSC）表现出高效的成骨分化潜力，并在植入的生物材料周围协调骨免疫微环境，通过Mdk/Lrp1配体-受体对。的抑制Mdk/Lrp1激活巨噬细胞和破骨细胞生成的促炎程序。同时，多个免疫细胞亚群之间也表现出密切的串扰镁合金你好MSC 通过分泌磷蛋白 1 (SPP1) 信号通路。本研究中表征的这些细胞特征和相互作用可以拓宽对生物材料介导的骨再生早期阶段功能性 MSC 亚群的理解，并为针对骨免疫调节的材料设计策略提供基础。