Injectable myocardial matrix-grapheme composite hydrogels for functional cardiac tissue engineering

 心脏病是包括美国在内的许多发达国家死亡和发病的主要原因。由于心肌细胞的终末分化和非增殖性质，心脏在梗死后无法再生和自我修复，由此产生的慢性心功能障碍往往导致5年内死亡。干细胞疗法涉及直接注射细胞到梗死组织最近已经获得了很多关注。然而，尽管这些疗法具有巨大的潜力，但压倒性的细胞死亡和移植细胞与周围宿主组织整合的有限能力限制了它们恢复心脏功能的有效性。拟议研究的目标是开发可注射的三维心肌基质-石墨烯复合支架，模拟健康心肌中看到的电，机械和生物化学环境线索，然后测试它们生成功能组织的能力。中心假设是石墨烯的高电导率将通过直接和间接（例如增加的间隙连接形成）机制增强动作电位传播，从而改善掺入的人诱导多能干细胞衍生的心肌细胞的功能。通过协同结合石墨烯和天然心肌基质的独特特性，我们的目标是创造一类新的三维支架，用于治疗目的的心脏组织工程。为此，我们将首先开发具有可调电气和机械性能的生物相容性和可注射心肌基质-石墨烯3D复合支架。然后，我们将评估导电三维复合支架在体外增强心肌细胞电生理功能的能力。

 DESCRIPTION: Heart disease is the leading cause of death and morbidity in many countries in the developed world, including the United States. Due to the terminally differentiated and non-proliferative nature of cardiomyocytes, the heart is unable to regenerate and repair itself after infarction, and the resulting chronic cardiac dysfunction often leads to death within 5 years. Stem cell-based therapies involving the direct injection of cells into infarcted tissue have garnered much attention recently. However, while these therapies hold tremendous potential, the overwhelming cell death and limited ability of graft cells to integrate with the surrounding host tissue limit their effectiveness at restoring cardiac function. The goal of the proposed research is to develop injectable, three- dimensional myocardial matrix-graphene composite scaffolds that mimic the electrical, mechanical and biochemical environmental cues seen in healthy myocardium, and then to test their ability to generate functional tissues. The central hypothesis is that the high conductivity of graphene will enhance action potential propagation through direct and indirect (e.g. increased gap junction formation) mechanisms, thereby improving the functionality of the incorporated human induced pluripotent stem cell-derived cardiomyocytes. By combining the unique characteristics of graphene and native myocardial matrices synergistically, we aim to create a new class of three-dimensional scaffolds for the engineering of cardiac tissues for therapeutic purposes. Towards this end, we will first develop biocompatible and injectable myocardial matrix-graphene 3D composite scaffolds with tunable electrical and mechanical properties. Then we will evaluate the capability of conductive 3D composite scaffolds in enhancing cardiomyocyte electrophysiological function in vitro.