基于微流控芯片的骨微环境模拟及成骨细胞IDG-SW3分化力生物学效应研究

项目名称： 基于微流控芯片的骨微环境模拟及成骨细胞IDG-SW3分化力生物学效应研究

项目编号： No.31500692

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 任丽

作者单位： 西北工业大学

项目金额： 20万元

中文摘要： 成骨细胞分化为成熟骨细胞在骨塑建和骨重建平衡中起关键作用。骨组织生化微环境和力学微环境是成骨细胞生存和分化的基础。目前基于二维培养的成骨细胞分化力生物学效应研究难以在生化微环境基础上阐明力学效应机制。微流控芯片“Organ-on-a-Chip”技术的发展，为研究生化微环境中成骨细胞分化及其力学效应机制开辟了新途径。.研究内容：①在微流控芯片上利用I型胶原蛋白-羟基磷灰石三维支架模拟骨生化微环境，利用芯片机械应力/流体剪切力控制系统模拟骨力学微环境；②以具有从成骨细胞至成熟骨细胞分化功能的IDG-SW3细胞为实验对象，研究模拟微环境中机械应力和流体剪切力对细胞分化的影响，获得细胞形态、细胞游离钙、分化标志蛋白、电压敏感性钙通道(VSCC)变化规律；③揭示VSCC在力学微环境调控成骨细胞分化中的作用。为阐明成骨细胞分化力学效应机制提供新的实验依据，为骨骼健康维护、废用性骨质流失防治提供新靶点。

中文关键词： 微流控芯片；生化微环境；力学微环境；成骨细胞IDG-SW3；分化

英文摘要： The differentiation of osteoblast into mature osteocyte is critical for bone modeling and remodeling. The biochemical and mechanical microenvironment of bone tissue is the foundation for osteoblast living and differentiation. At present, researches on the response of osteoblast differentiation to mechanical cues is mainly based on the two-dimensional cell culture system, which is not appropriate for clarification the mechanical responses and mechanisms associated with the biochemical microenvironment. The development of microfluidics-based “Organ-on-a-Chip” technology has provided an efficient strategy to investigate the mechanical cues involved osteoblast differentiation and the related mechanism in the biochemical microenvironment. . In this proposal, (1) in the microfluidic devices, the bone biochemical microenvironment will be simulated by the three dimensional scaffold composed of type-I collagen and hydroxyapatite, and the bone mechanical microenvironment will be simulated by the mechanical stress and fluid shear stress control systems integrated in the devices; (2) The IDG-SW3 osteoblastic cells which replicate osteoblast-to-late-osteocyte differentiation in vitro will be used to study the effect of mechanical stress and fluid shear stress on osteoblast differentiation in simulated bone microenvironment, the changes of cell morphology, intercellular Ca2+ concentration, expression of differentiation-related biomarkers and voltage-sensitive calcium channel (VSCC) will be monitored; (3) The role of VSCC in mechanical microenvironment regulated osteoblast differentiation will be revealed. This research will provide essential experimental evidences for clarifying the mechanobiological mechanisms of osteoblast differentiation, and will also identify a potential target for maintaining bone health, prevention and treatment of disuse-induced bone loss.

英文关键词： Microfluidic device;Biomechanical microenvironment;Mechanical microenvironment;IDG-SW3 osteoblastic cell;Differentiation