Current Advances and Future Directions of Pluripotent Stem Cells-Derived Engineered Heart Tissue for Treatment of Cardiovascular Diseases.

Cardiovascular diseases resulting from myocardial infarction (MI) remain a leading cause of death worldwide, imposing a substantial burden on global health systems. Current MI treatments, primarily pharmacological and surgical, do not regenerate lost myocardium, leaving patients at high risk for heart failure. Engineered heart tissue (EHT) offers a promising solution for MI and related cardiac conditions by replenishing myocardial loss. However, challenges like immune rejection, inadequate vascularization, limited mechanical strength, and incomplete tissue maturation hinder clinical application. The discovery of human-induced pluripotent stem cells (hiPSCs) has transformed the EHT field, enabling new bioengineering innovations. This review explores recent advancements and future directions in hiPSC-derived EHTs, focusing on innovative materials and fabrication methods like bioprinting and decellularization, and assessing their therapeutic potential through preclinical and clinical studies. Achieving functional integration of EHTs in the heart remains challenging due to the need for synchronized contraction, sufficient vascularization, and mechanical compatibility. Solutions such as genome editing, personalized medicine, and AI technologies offer promising strategies to address these translational barriers. Beyond MI, EHTs also show potential in treating ischemic cardiomyopathy, heart valve engineering, and drug screening, underscoring their promise in cardiovascular regenerative medicine.