Engineering cardiac tissue: The role of topographic cues in cardiomyocytes

Cardiovascular diseases represent a leading cause of mortality on a global scale. Engineered cardiac tissue applied as in vitro model have great potential on discovering myocardium pathology mechanisms and developing new drugs. Contemporary in vitro models, particularly traditional 2D cultures, face challenges in accurately replicating the complex architecture and functional behaviors of native myocardium. In this context, topographical cues-engineered through various fabrication methods, including direct laser writing, lithography, etching, self-organization, electrospinning, and 3D printing-have emerged as essential tools in cardiac tissue engineering (CTE). These cues can be incorporated into both 2D substrates and 3D scaffolds, significantly influencing the adhesion, morphology, migration, and functional properties of cardiomyocytes (CMs), including electrical conduction and contractility. In this paper, we searched PubMed, Web of Science, and CNKI databases with keywords "cardiac tissue engineering, topography, nano pattern, micro pattern, biomaterials, cell orientation" for relevant studies published between 2010 and 2025. This work retrieved 127 studies, aiming to provide recent advancements in the application of topographical cues to influence the behavior of CMs and to establish a foundation for future developments in cardiac tissue engineering. Additionally, the review addresses the challenges associated with creating fully functional engineered cardiac tissues and offers perspectives on future advancements in this rapidly evolving field, emphasizing the necessity to enhance the performance of engineered cardiac tissues for disease modeling and regenerative therapies.