Injectable MXene conductive hydrogel improves myocardial infarction through scavenging ROS and repairing myocardium electrical integrity

Abstract

Myocardial infarction (MI) caused by ischemia and hypoxia microenvironment leads to irreversible death of cardiomyocytes, in which excessive oxidative stress plays a key role. Moreover, MI breaks the effective conduction of electrical signals in myocardial tissue, leading to cardiac systolic and diastolic dysfunction, and subsequently adverse ventricular remodeling. Therefore, scavenging reactive oxygen species (ROS) and repairing myocardium electrical integrity are two key issues in MI treatment. In this study, we embedded MXene nanosheets (Ti3C2) into temperature-sensitive extracellular matrix (ECM) hydrogels to prepare antioxidant/conductive hydrogels (E-MXene). E-MXene efficiently eliminated ROS in vitro, and improved calcium signaling synchronization of human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) because of remarkable antioxidant and conductivity properties. Meanwhile, the upregulation of Connexin43(Cx43) confirmed that MXenes enhanced electrical conduction between hiPSC-CMs. The injection of E-MXene in the MI region of mice soon after surgery was found to reduce ROS and cardiomyocyte apoptosis in the early stage of MI, as well as enhanced the electrical signal transmission in infarcted tissue during the late stage of MI. The cardiac function and structure were improved 28 days post-MI. Therefore, the E-MXene combined ROS scavenging with tissue electrical integrity improvement, thus providing theoretical bases and new ideas for the treatment of MI.