Multifactorial approaches to enhance maturation of human iPSC-derived cardiomyocytes

•Maturation of hiPSC-CMs is key as pluripotent stem cell-derived cardiomyocytes initially express a foetal phenotype.•A biomimetic environment is needed with multiple stimuli to achieve higher maturation of hiPSC-CMs.•Electrospun scaffolds could recapitulate the natural 3D environment for tissue engineering.•Electrically conductive polymers are essential for cardiac tissue engineering.•3D printing and bioreactors support the long-term cell culture of hiPSC-CMs. Cardiovascular diseases are the leading cause of death worldwide. Several strategies – small molecules, gene therapy, surgeries, cardiac rehabilitation – have been developed to treat patients with cardiac disorders or to prevent the disease. A novel promising tool is the application of induced pluripotent stem cell-derived human cardiomyocytes; however, their clinical application is hampered by their fundamentally immature characteristics. Although several approaches were recently proven to support certain aspects of cardiac maturation, it has been discovered that any kind of stimulus itself is insufficient to induce proper maturation of these cardiomyocytes. Therefore, researchers have developed multifactorial approaches linking biotechnology, life sciences and material sciences toolsets. In this review, we summarise the current state-of-the-art methodologies in cardiac differentiation and maturation with the application of biocompatible materials and automated cell culture systems combined with various electrical, mechanical, topological, and biochemical stimuli.