三维基质应力松弛特性通过integrin/FAK/MMP信号通路调控血管新生的机制研究

血管新生是胚胎发育及肿瘤血管化的重要血管发生机制之一，其发生发展过程与基质的三维力学微环境紧密相关。尽管基质刚度对血管新生的调控作用备受关注，但基质应力松弛性能对血管新生的影响及调控机制尚不明确。结合申请人在动态水凝胶开发、体外血管新生模型构建及其分子生物学机制探究上的研究基础，针对基质应力松弛性能调控血管新生的规律和机制不清楚这一科学问题以及如何构建体外三维应力松弛微环境的技术挑战，本项目拟：通过模拟在体血管组织基质刚度及生物活性，基于动态水凝胶的设计原理，体外构建具有低刚度、独立可控应力松弛性能的三维力学微环境平台；通过建立体外血管新生三维培养模型，阐明基质应力松弛特性对血管新生的影响规律；通过分子生物学实验，揭示血管新生过程通过integrin/FAK/MMP信号通路感知应力松弛微环境的力学生物学转导机制。项目研究结果有望为血管类相关疾病的发病机理和防治方案提供新的力学生物学依据。

Vasculogenesis is the process of novel blood vessel formation, which has been found to occur during embryogenesis or tumor vascularization. Increasingly, matrix stiffness is being recognized as an indispensable characteristic impacting vasculogenesis. However, it is unknown how matrix stress relaxation influences vasculogenesis, and the corresponding molecular pathway remains elusive. Based on our expertise on development of dynamic hydrogels, in vitro modeling of vasculogenesis and mechanotransduction, this project aims to develop a tunable 3D stress relax hydrogel with mimicking native matrix of vascular tissues based on dynamic covalent chemistry; to explore the effects of matrix stress relaxation on vasculogenesis through the constructed 3D vascular tissue culture model; and to reveal the underlying integrin/FAK/MMP pathways of vascular morphogenesis by using molecular biology experiments. The results from this project would provide new insights and treatments of vascular dieseases from the biomechanical and mechanobiological perspectives.