载石墨烯的定向明胶/PCL纳米纤维材料构建组织工程化房室传导束的实验研究

Atrioventricular conduction block is a serious clinical problem. Currently, in addition to permanent pacemaker placement, there is no other preferable therapeutic method to cure this disease. Although the effectiveness of cardiac pacemaker implantation as palliative treatment seemed irrefutable, but its long-term efficacy is not optimistic, especially in terms of children. To explore an innovative, not dependent on artificial cardiac pacemaker, sustainable and effective treatment for atrioventricular conduction block, has extremely important clinical significance. This project will load grapheme with extraordinary electric conductivity into aligned gelatin/PCL nanofibrous scaffold which was established in our previous research by electrospinning in order to construct tissue engineered conduction bundle. The growth activity of the scaffold can be acquired through the new tissue engineering strategy that is purely material implantation technology. The electric conductivity of scaffold is enhanced by loading with graphene. At the same time, we will study the biocompatibility of scaffolds through the cell and animal experiments; Finally, the electrical conduction efficiency of regeneration tissue formed by the implantation of this scaffold in atrioventricular groove can be verified by complete atrioventricular block in dog model. If this study can achieve the expected goal, it will create a brand new route to constructe tissue-engineered atrioventricular conduction bundle and promote the development of biological therapy for atrioventricular block.

心脏房室间电传导的中断是很严重的临床问题，目前除了安装心脏起搏器外没有更好的治疗方法。尽管心脏起搏器植入作为姑息性治疗的有效性不容置辩，但其长期疗效不容乐观，尤其是对于儿童而言。探索一种创新性的、不依赖于人工心脏起搏器的、可持续有效的房室传导阻滞治疗方法，有着极其重要的临床意义。本项目拟通过静电纺丝技术，将具有非凡导电性能的石墨烯载入我们先前研发的定向明胶/聚己内酯（PCL）纳米纤维支架材料以构建组织工程化电传导束，支架材料的生长活性通过新的组织工程策略即纯材料植入技术获得，支架材料的电传导性能因为石墨烯的载入而增强；同时通过细胞实验和动物实验对材料的生物相容性进行研究；最后通过犬完全性房室传导阻滞模型验证这一植入于心脏房室沟的支架材料及随之形成的新生组织的电传导功效。本研究如能达到预期目标将为构建组织工程化电传导束开创新的途径，推动房室传导阻滞生物治疗的发展。

完全性心脏房室传导阻滞是很严重的临床问题，安装心脏起搏器是目前最有效的治疗方法。尽管心脏起搏器植入的必要性毋庸置疑，但其对心脏传导模式的不完全模拟和长期监控的需要，让它的不良反应也不容忽视。因此，探索一种创新的，不依赖于人工起搏的，可持续的，恢复房室间正常传导的治疗方法，具有极重大的意义。本项目通过静电纺丝技术，结合石墨烯的超强导电性能，制备出可作为工程化电传导束的载石墨烯明胶/PCL纳米纤维材料。通过体外细胞实验和体内生物相容性测试，明确最佳的石墨烯质量分数的材料配方。体外实验证明定向明胶/PCL材料有利于心肌细胞的电传导，石墨烯的添加能显著增强材料上细胞的电传导活跃度。动物心脏房室沟植入定向明胶/PCL纳米纤维材料构成的工程化电传导束，动物出现房室旁路传导特征，提示了该材料作为修复房室传导阻滞的潜在应用价值，为进一步的实验验证和转化应用提供了理论基础。该项目对房室传导阻滞治疗提供了重要思路和依据。