Wang Yuexin, Chen Shu, Fan Wenwen, Zhang Sixian, Chen Xi
Key Laboratory for Ultrafine Materials of Ministry of Education, Frontiers Science Center for Materiobiology and Dynamic Chemistry, Engineering Research Center for Biomedical Materials of Ministry of Education, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai 200237, China.
Micromachines (Basel). 2025 Apr 30;16(5):539. doi: 10.3390/mi16050539.
Osteogenesis-angiogenesis coupling, a dynamic and coordinated interaction between skeletal and vascular cells, is essential for fracture healing. However, the effects of these cell ratios and their interactions under microfluidic perfusion and paracrine signaling on osteogenesis-angiogenesis coupling have rarely been reported. In this study, dynamic and static models of osteogenesis-angiogenesis coupling were developed and the osteogenic and angiogenic effects of the two models were compared. Static co-cultures of MC3T3-E1 and bEnd.3 cells in Transwell inserts showed a cell ratio-dependent reciprocal relation: a ratio of 1:1 (MC3T3-E1:bEnd.3) favored osteogenesis, whereas a ratio of 2:1 (MC3T3-E1:bEnd.3) promoted angiogenesis. On that basis, we developed an osteogenesis-angiogenesis coupling chip based on microfluidic technology. The microfluidic perfusion within the chip further enhanced the mineralizing effect of osteoblasts and the angiogenic effect of endothelial cells, respectively, and increased the secretion of vascular endothelial growth factor (VEGF) and bone morphogenetic protein-2 (BMP-2) compared to the static Transwell insert model. The results suggest that the microfluidic chip enhanced the potential of osteogenesis-angiogenesis coupling mediated by paracrine signaling. Overall, the chip is not only a powerful model for understanding bone-vascular interaction but also a scalable platform for high-throughput drug screening and personalized therapy development for fractures.
骨生成-血管生成偶联是骨骼细胞与血管细胞之间动态且协调的相互作用，对骨折愈合至关重要。然而，在微流控灌注和旁分泌信号作用下，这些细胞比例及其相互作用对骨生成-血管生成偶联的影响鲜有报道。在本研究中，构建了骨生成-血管生成偶联的动态和静态模型，并比较了两种模型的成骨和血管生成作用。Transwell小室中MC3T3-E1细胞和bEnd.3细胞的静态共培养显示出细胞比例依赖性的相互关系：1:1（MC3T3-E1:bEnd.3）的比例有利于成骨，而2:1（MC3T3-E1:bEnd.3）的比例促进血管生成。在此基础上，我们基于微流控技术开发了一种骨生成-血管生成偶联芯片。与静态Transwell小室模型相比，芯片内的微流控灌注分别进一步增强了成骨细胞的矿化作用和内皮细胞的血管生成作用，并增加了血管内皮生长因子（VEGF）和骨形态发生蛋白-2（BMP-2）的分泌。结果表明，微流控芯片增强了由旁分泌信号介导的骨生成-血管生成偶联的潜力。总体而言，该芯片不仅是理解骨-血管相互作用的有力模型，也是用于骨折高通量药物筛选和个性化治疗开发的可扩展平台。
