基于导电纳米材料和磁纳米颗粒的工程化心肌组织构建及血管化研究

Cardiac tissue engineering provides a new strategy for the treatment of ischemic heart diseases. However, there are two crucial problems existed in engineered cardiac tissues: the deficiency of electrical coupling among cardiomyocytes within the engineered tissues and the insufficiency of vascularization, with limited new strategies available. In recent years, many studies indicated that conductive nano-materials can improve electrical coupling among cardiomyocytes, and the magnetic nanoparticles have significant prospect in cell manipulation, which provides a brand new strategy for the vascularization of engineered tissues. This study intends to use conductive nano-material graphene as scaffold, primarily cultured cardiomyocytes and brown adipose derived cardiac stem cells as seeding cells to reconstruct engineered cardiac tissues to enhance cell-cell electrical coupling. After that, we will prepare magnetic nanoparticles mixed with zinc (Zn-MNPs) and combined with ephrin B2 antibodies to regulate ephrin cell signaling pathway of endothelial cells to facilitate the prevasculariztion of the engieered cardiac tissues. Then, the prevascularized engineered cardiac tissues will be transplanted into the infarcted heart of the animal models to envaluate the capabilities of myocardium repairment, cell-cell electrical coupling and in vivo vascularization of the engineered tissues. This study aimed to get some new perspect in the problems restricting the development of cardiac tissue engineering as well as provide a new scaffold in reconstruction and new method in vascularization.

心肌组织工程研究为缺血性心脏病的治疗提供了新的策略和手段。然而，工程化心肌组织仍存在心肌细胞间电偶联不足、血管化程度低且可供选择方法有限等问题。近年的研究表明，导电纳米材料对促进心肌细胞电偶联具有重要作用，而磁纳米颗粒则在细胞操控方面展现了良好前景，为血管化研究提供了全新的方法。本研究拟采用石墨烯导电纳米材料为支架，棕色脂肪来源的心脏干细胞为种子细胞，体外构建工程化心肌组织；制备锌磁纳米颗粒（Zn-MNPs）且与ephrinB2抗体结合，并将其复合应用到工程化心肌组织中，使其发挥对再造心肌组织中血管内皮ephrin细胞信号通路的调控作用，促进其血管化。在此基础上，将上述构建的工程化心肌组织进行心梗动物模型的体内移植，进一步探索其对受损心肌的修复能力、电整合能力与血管化水平。本项目研究有望在制约工程化心肌进一步发展的瓶颈问题上取得明显突破，并为心肌体外构建研究提供新型支架材料以及血管化方法。