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

 描述：在包括美国在内的许多发达国家，心脏病是导致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，心肌梗死后心脏不能自我再生和修复，由此导致的慢性心功能不全往往导致5年内死亡。以干细胞为基础的治疗，包括将细胞直接注射到脑梗塞组织中，最近得到了很大的关注。然而，尽管这些疗法具有巨大的潜力，但绝大多数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。这项拟议的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，模拟健康心肌中的电、机械和生化环境信号，然后测试其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机制(如增加缝隙连接形成)增强动作电位的传播，从而改善被掺入的人诱导多能干细胞来源的心肌细胞的功能。通过协同结合石墨烯和天然心肌基质的独特特性，我们的目标是为治疗目的的心脏组织工程创造一类新的三维支架。为此，我们将首先开发生物相容性和可注射的心肌基质-石墨烯3D复合支架，具有可调的电和机械性能。然后，我们将评估导电3D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.