Progress in engineering functional cardiac tissues from iPSC-derived cardiomyocytes: advances in construction and applications.

Engineered cardiac tissue (ECT) has emerged as a transformative platform for modelling cardiac diseases, drug screening, and regenerative therapies. Among the various strategies for ECT construction, cardiomyocytes derived from human induced pluripotent stem cells (iPSC-CMs) have gained prominence due to their capacity to overcome critical limitations of primary cardiomyocyte sources, such as species-specific differences, limited tissue availability, and ethical concerns. In this review, we present a comprehensive overview of recent advancements in the use of iPSC-CMs for ECT development. We begin by outlining current methodologies for differentiating iPSC into cardiomyocytes, followed by an evaluation of key tissue engineering approaches, including scaffold-based, scaffold-free, and biofabrication techniques, that are used to assemble functional cardiac constructs in vitro. Special attention is given to the comparative advantages and challenges of these platforms. We highlight emerging applications of iPSC-CM-based ECTs, focusing on heart-on-a-chip systems for disease modelling and high-throughput drug testing, as well as cardiac patches for myocardial repair. Finally, we highlight major challenges, such as iPSC-CM immaturity, poor vascularization, and limited electromechanical integration, and discuss emerging bioengineering strategies to overcome these barriers and advance the clinical translation of engineered cardiac tissues. STATEMENT OF SIGNIFICANCE: ECT is an increasingly sophisticated platform with significant potential for cardiac disease modelling, drug screening, and regenerative therapy. This review provides a comprehensive analysis of the emerging role of human iPSC-CMs in ECT development, with emphasis on advanced differentiation protocols, biomaterial-guided tissue assembly, and cutting-edge biofabrication strategies. By critically evaluating scaffold-based, scaffold-free, and bioprinting approaches, we offer an integrated perspective on the fabrication of functional cardiac constructs. In addition, we discuss translational applications-including heart-on-a-chip systems and myocardial patches-and examine key challenges such as iPSC-CM immaturity, limited vascularization, and suboptimal electromechanical coupling. This review presents a timely synthesis at the intersection of stem cell biology, biomaterials science, and tissue engineering, intended to guide the design of next-generation therapeutic cardiac tissues.