Successfully engineering a functional, human, myocardial pump would represent a therapeutic alternative for the millions of patients with end-stage heart disease and provide an alternative to animal-based preclinical models. Although the field of cardiac tissue engineering has made tremendous advances, major challenges remain, which, if properly resolved, might allow the clinical implementation of engineered, functional, complex 3D structures in the future. In this Review, we provide an overview of state-of-the-art studies, challenges that have not yet been overcome and perspectives on cardiac tissue engineering. We begin with the most clinically relevant cell sources used in this field and discuss the use of topological, biophysical and metabolic stimuli to obtain mature phenotypes of cardiomyocytes, particularly in relation to organized cytoskeletal and contractile intracellular structures. We then move from the cellular level to engineering planar cardiac patches and discuss the need for proper vascularization and the main strategies for obtaining it. Finally, we provide an overview of several different approaches for the engineering of volumetric organs and organ parts — from whole-heart decellularization and recellularization to advanced 3D printing technologies.
In this Review, Dvir and colleagues summarize and discuss the state-of-the-art technologies that enable the bioengineering of functional cardiac tissues and discuss current and future applications and limitations.
Key points: The successful engineering of functional, human, myocardial tissues would represent a therapeutic alternative for the millions of patients with end-stage heart disease.The well-organized, characteristic structure of the heart across its multiple scales is crucial for its mechanical function; therefore, recapitulating these structure–function relationships in engineered myocardial tissues is necessary.Developing integrative maturation protocols and quantitative tools to assess the maturation of human induced pluripotent stem cell-derived cardiomyocytes is needed to produce cells with a mature phenotype that can successfully integrate with the host tissue.Although the engineering of anisotropic, thick, vascularized tissue patches has been demonstrated using various fabrication techniques, their clinical implementation is still hampered by their poor integration with host tissue.Fabricating 3D, volumetric, myocardial tissues could address the urgent need of patients with end-stage heart failure for heart donation and is therefore an active and evolving field of research.