基于人诱导多能干细胞及结构色水凝胶构建“可视化”心脏芯片的研究

心血管疾病严重威胁人类健康，近年来兴起的心脏芯片为体外研究心脏疾病，发育再生，筛选有效药物等提供了强有力的工具。然而，心脏芯片构建中还面临支架材料不理想，种子细胞有待优化及缺乏简单实时动态监测芯片功能的方法等问题。针对上述问题，本课题组前期研究证实：利用带沟槽表面微结构的GelMA结构色水凝胶，有利于促进人诱导多能干细胞来源的心肌前体细胞进一步向心肌细胞分化成熟，同时，通过颜色的变化可以实时“可视化”的反应心肌细胞的跳动频率和强度。本项目在此基础上，提出进一步改进GelMA结构色表面微结构和软硬度，寻找更为有利于促进心肌分化成熟的支架材料；同时，研究上述支架材料对不同分化阶段的诱导多能干细胞的心肌诱导分化能力，寻找构建心脏芯片的最优种子细胞来源。最后，构建实时“可视化”心脏芯片，实现动态监测心肌细胞分化过程，为研究心脏发育，药物筛选，疾病治疗提供全新工具和手段。

Cardiovascular disease is the number one killer seriously threatening human health. The heart-on-a-chip is emerging as a potential tool for investigating this type of disease and screening active drugs in recent years. At present, the construction of the heart-on-a-chip also faces problems such as no ideal scaffold materials, seed cells to be optimized, and the lack of a simple real-time dynamic monitoring chip function. To overcome the above mentioned problems, previous research by our research group has confirmed that the use of a GelMA structural color hydrogel with a grooved surface microstructure is beneficial to promoting the differentiation of cardiac precursor cells from human induced pluripotent stem cells into cardiomyocytes. The color change can "visualize" the beating frequency and intensity of cardiomyocytes in real-time. On the basis of this project, on the one hand, it is proposed to further improve the surface microstructure and hardness of the GelMA structure color , and to find scaffold materials that can further facilitate the differentiation and maturation of cardiomyocytes; on the other hand, to study the induction of different scaffold materials by different scaffolding stages, the induction of pluripotent stem cells to myocardial differentiation and maturation, and to find the source of ideal seed cells for constructing a heart-on-a-chip. Finally, a structural color hydrogel combined with ideal cell phases is used to construct a real-time "visualized" heart-on-a-chip, which dynamically monitors cardiomyocytes differentiation process and drug screening, and provides new tools and methods for studying cardiac development, drug screening, and disease treatment.