基底硬度与适配体Apt19S浓度协同调控MSCs成骨分化的力学生物学机制

In the clinical treatment of bone defects, the bone repairing speed and effect are affected by the mechanical-biochemical microenvironment of extracellular matrix (ECMs). In order to improve the repairing effect, it is urgent to study the synergistic effect of mechanical- biochemical factors to the recruitment behavior of MSCs and osteogenic differentiation mechanism. The project proposes to modify the aptamers (Apt19S) with specific recognition properties to MSCs into the polyvinyl alcohol (PVA) hydrogel, obtaining the ECMs with efficiently recruitment ability to MSCs and studying the biological behaviors of MSCs, such as the morphology, adhesion, proliferation and osteogenic differentiation under single and coordination effects of matrix hardness and aptamer concentration. Further investigation focus on the effect law of aptamers (Apt19S) to the RhoA-Rock-ERK signaling pathway which mediated by the matrix hardness, and the mechanobiology mechanism of aptamers (Apt19S) concentration and matrix hardness coordinately regulate of the osteogenic differentiation of MSCs. This project is helpful to the revealing of the MSCs differentiation mechanism induced by mechanical and biochemical factors, and could provide reference for the optimal designing of bone repairing ECMs.

临床骨缺损治疗中，骨修复速度和效果受到骨髓间充质干细胞（MSCs）外基质（ECMs）的力-生化微环境影响。为了进一步提高骨修复效果，迫切需要研究ECMs的力、生化因子对MSCs的募集行为及骨向分化诱导机制的影响。本项目拟将具有特异识别MSCs功能的适配体（Apt19S）修饰到聚乙烯醇（PVA）水凝胶内，得到对MSCs具有高效募集能力的ECMs，并研究基底硬度与适配体（Apt19S）浓度单独及协同调控下，MSCs的形态、黏附、增殖、成骨分化等生物学行为；进一步深入研究适配体通过干预基底硬度介导的RhoA-Rock-ERK信号通路进而影响MSCs成骨分化的规律，总结适配体Apt19S浓度与基底硬度协同调控MSCs成骨分化的力学生物学机制。本项目有助于揭示力学和生化因素诱导MSCs成骨分化的机制，也可为骨修复用ECMs的优化设计提供参考。

本项目研究了ECMs的力、生化因子对MSCs的募集行为及骨向分化诱导机制的影响。将具有特异识别MSCs功能的适配体（Apt19S）修饰到聚乙烯醇（PVA）水凝胶内，得到了对MSCs具有高效募集能力的ECMs，并研究了基底硬度与适配体（Apt19S）浓度单独及协同调控下，MSCs的形态、黏附、增殖、成骨分化等生物学行为；进一步深入研究了适配体通过干预基底硬度介导的RhoA-Rock-ERK信号通路进而影响MSCs成骨分化的规律，总结了适配体Apt19S浓度与基底硬度协同调控MSCs成骨分化的力学生物学机制。本项目有助于揭示力学和生化因素诱导MSCs成骨分化的机制，也可为骨修复用ECMs的优化设计提供参考。