Three-Dimensional Bioprinted Vascularized Cardiac Tissue: Stem Cell Differentiation Protocols and Electrophysiological Integration for Myocardial Infarction Regeneration

Abstract

Myocardial infarction remains a leading cause of mortality worldwide, with current therapeutic interventions providing limited regenerative capacity for damaged cardiac tissue. Three-dimensional bioprinting has emerged as a revolutionary approach to engineer functional cardiac tissue constructs that recapitulate the complex architecture and electrophysiological properties of native myocardium. This comprehensive review examines the current state of three-dimensional bioprinted vascularized cardiac tissue, with particular emphasis on stem cell differentiation protocols and electrophysiological integration strategies for myocardial infarction regeneration. We critically analyze the biomaterials employed in cardiac bioprinting, discuss advanced differentiation protocols for pluripotent stem cells into cardiomyocytes, and explore vascularization strategies essential for tissue survival and integration. Furthermore, we examine the electrophysiological maturation requirements and functional assessment methodologies that determine the clinical viability of bioprinted cardiac constructs. The integration of biomimetic approaches, including the incorporation of conductive biomaterials and microfabrication techniques, demonstrates promising potential for generating electrically integrated cardiac patches capable of synchronizing with host myocardium. Current challenges, including achieving appropriate cellular maturity, establishing functional vascularization, and ensuring long-term graft survival, are discussed alongside emerging solutions and future directions in the field.