仿生细胞力-形-电微环境的构建及其应用于心肌组织工程的研究

基于干细胞的心肌组织工程被视为未来治疗心血管疾病最有希望的手段。但是，因目前干细胞衍生的体外心肌组织存在成熟度低、易导致心律失常等问题，使得该技术的临床转化面临严峻挑战，亟需发展高效的体外细胞微环境平台，以研究各种微环境信号对干细胞行为的影响规律和作用机制，指导如何提高干细胞向心肌细胞分化的成熟度、实现功能性心肌组织的体外重建。虽然至今已有多种体外细胞微环境平台被用于心肌组织的体外构建，但是这些平台仅能提供单一因素、简单模式的刺激，因而导致所培养的心肌细胞在结构和功能上与体内成熟的心肌细胞存在较大差距，尚不能实现受损心肌组织的有效修复。针对这一现状，本项目拟构建一种可动态调控的体外细胞力-形-电耦合微环境平台，更全面地模拟心肌细胞生理微环境，深入研究主要物理因素在干细胞心肌向分化成熟过程中的调控机制，以指导体外构建具有生理功能的心肌组织，为基于干细胞的心肌组织工程的临床应用奠定基础。

The stem cell-based cardiac tissue engineering represents a potential therapy for patients with cardiovascular diseases. Despite exciting progress, its clinical translation has been hampered by the immature nature of the stem cell-derived cardiomyocytes which may pose arrhythmic risk. There is an urgent need for an efficient platform that recreates physiologically relevant stem cell microenvironments to enhance our understanding of the impact of a number of physical cues on stem cell differentiation into cardiac cells and promote functional maturation of the stem cell-derived cardiomyocytes. Towards this goal, some cell microenvironment platforms have been developed for the production of the stem cell-derived cardiac tissues. However, fthe stem cells or stem cell-derived cardiomyocytes in these platforms are only exposed to mono-stimuli factor with simple modes, which results in the functionality of the generated tissues is still unable to match that of native cardiac tissue. To achieve greater cardiomyocyte maturation and function in vitro, this program will develop a novel cell microenvironment platform that can provide mechanical, electrical stimulation and topographical cue in a combinatorial and dynamic manner to more closely mimic nature cardiac microenvironment. Benefitting from controlling a combination of multiple physical environmental cues, this platform will help elucidate the effects of mechanical, electrical, and topographical signals on stem cell differentiation into cardiac cells and functional maturation of the stem cell-derived cardiomyocytes, and then bring stem cell-based cardiac tissue engineering closer to fruition.