Electrospun nanofiber scaffolds for myocardial repair: Mechanistic design, preclinical advances, and translational perspectives

Myocardial infarction (MI) remains a leading cause of global mortality and is characterized by irreversible cardiomyocyte loss, electrical uncoupling, fibrotic remodeling, and progressive ventricular dysfunction that ultimately leads to heart failure. Current therapeutic strategies primarily focus on limiting infarct expansion but are unable to regenerate functional myocardium or restore electromechanical synchronization. Electrospun nanofiber scaffolds have emerged as a versatile platform in cardiac tissue engineering owing to their nanoscale architectural similarity to the extracellular matrix (ECM), tunable anisotropy, and capacity to incorporate electroconductive, angiogenic, and cytoprotective functionalities within a biomimetic framework. This review critically examines recent advances in the design of electrospun nanofiber scaffolds for ischemic cardiac repair, with emphasis on material selection, fiber alignment strategies, conductive composite integration, and controlled delivery of growth factors, stem cells, and therapeutic agents. Particular attention is given to how these scaffolds address key post-infarction biological bottlenecks, including electrical discontinuity, impaired vascularization, oxidative stress, and structural disorganization of the myocardium. Preclinical studies demonstrate improved cardiomyocyte maturation, enhanced gap junction formation, increased angiogenesis, and partial functional recovery in small-animal models. However, critical challenges remain, including insufficient benchmarking of scaffold conductivity against native myocardial tissue, limited long-term electrophysiological safety evaluation, and a lack of validation in large-animal models. Emerging translational strategies such as epicardial cardiac patches, injectable nanofibrous constructs, and gene-activated scaffolds are discussed together with regulatory, immunological, and manufacturing considerations that must be addressed for clinical translation. By integrating advances in biomaterials engineering with principles of regenerative cardiology, electrospun nanofiber scaffolds represent a promising yet still evolving approach toward achieving clinically viable myocardial regeneration following infarction.