骨髓间充质干细胞(bone marrow mesenchymal stem cell, BMSC)与水凝胶支架的相互作用是骨组织工程领域的研究热点。此文系统梳理了水凝胶支架调控BMSC成骨分化的分子机制,聚焦其在协调信号通路、改善免疫微环境及引导细胞行为方面的作用。研究表明,水凝胶通过其物理化学特性(如刚度、成分)调节Wnt、腺苷酸活化蛋白激酶- UNC-51样激酶1-自噬轴、刺猬蛋白及Nel样分子1等关键信号网络,进而激活Runt相关转录因子2、Osterix等成骨核心转录因子。功能化水凝胶还可负载IL-4等免疫调节因子或生物活性离子,诱导巨噬细胞向M2型极化,抑制炎症并释放血管内皮生长因子、骨形态发生蛋白2等,重塑促再生免疫微环境,同时增强细胞黏附与定向迁移。这些机制共同克服了炎症-成骨负反馈及干细胞归巢效率低的问题,为智能骨修复支架的临床转化提供了理论支撑。此文还进一步对比了天然、合成及复合水凝胶作为调控载体的性能差异,为材料选择提供了依据。
The interaction between bone marrow mesenchymal stem cells (BMSCs) and hydrogel scaffolds is a research hotspot in the field of bone tissue engineering. In this paper, the molecular mechanism of hydrogel scaffold regulating osteogenic differentiation of BMSC is systematically reviewed, focusing on its role in coordinating signaling pathways, improving immune microenvironment and guiding cell behavior. Studies have shown that hydrogels regulate key signaling networks such as Wnt, adenosine monophosphate-activated protein kinase-UNC-51-like kinases 1-autophagy axis, Hedgehog and Nel-like molecule-1 through their physical and chemical properties such as stiffness and composition, thereby activating Runt-related transcription factor 2, Osterix, and other osteogenic core transcription factors. Functionalized hydrogels can also be loaded with immunomodulatory factors or bioactive ions such as IL-4 to induce macrophage polarization to M2 type, inhibit inflammation and release factors such as vascular endothelial growth factor and bone morphogenetic protein 2, reshape the pro-regenerative immune microenvironment, and enhance cell adhesion and directional migration. These mechanisms jointly overcome the problems of inflammation-osteogenesis negative feedback and low stem cell homing efficiency, and provide theoretical support for the clinical transformation of intelligent bone repair scaffolds. In this paper, the performance differences of natural, synthetic, and composite hydrogels as regulating carriers are further compared to provide a basis for material selection.