Bioactive Peptide-Based Electroactive Hydrogels for Myocardial Infarction Treatment via Electrical and Microenvironmental Regulation

Postmyocardial infarction (MI), oxidative stress and insufficient blood supply contribute to impaired cardiac repair, while the subsequent formation of fibrotic scar tissue, characterized by poor electrical conductivity, further exacerbates cardiac dysfunction. Here, we compounded the angiogenesis-promoting peptide (KRX) with effective pro-angiogenic effects and the conductive material carboxylated carbon nanotubes (CNTs) through electrostatic interaction, thus preparing CNT/KRX. Subsequently, we prepared the electroactive hydrogel (Gel@CK) by compounding CNT/KRX with the natural polysaccharide hydrogel. This design endows the hydrogel with both electrical conductivity and the function of promoting angiogenesis. <i>In vitro</i>, the hydrogel showed effective scavenging of reactive oxygen species (ROS), cell compatibility, promoted endothelial cell angiogenesis. In the MI model, the hydrogel significantly promoted angiogenesis and mitigated oxidative stress. Furthermore, it effectively shortened the Q wave, R wave and S wave (QRS) interval and enhanced tissue electrical integration. The cardiac function indices measured by echocardiography tests and the immunohistochemical analyses indicate that the hydrogel has improved the cardiac function and reduced the infarct size. This composite hydrogel demonstrates remarkable therapeutic potential for MI and cardiovascular diseases through dual modulation of the myocardial microenvironment and electrical activity.