Abstract
Cardiac tissue engineering aims at creating contractile structures that can optimally reproduce the features of human cardiac tissue. These constructs are becoming valuable tools to model some of the cardiac functions, to set preclinical platforms for drug testing, or to alternatively be used as therapies for cardiac repair approaches. Most of the recent developments in cardiac tissue engineering have been made possible by important advances regarding the efficient generation of cardiac cells from pluripotent stem cells and the use of novel biomaterials and microfabrication methods. Different combinations of cells, biomaterials, scaffolds, and geometries are however possible, which results in different types of structures with gradual complexities and abilities to mimic the native cardiac tissue. Here, we intend to cover key aspects of tissue engineering applied to cardiology and the consequent development of cardiac organoids. This review presents various facets of the construction of human cardiac 3D constructs, from the choice of the components to their patterning, the final geometry of generated tissues, and the subsequent readouts and applications to model and treat cardiac diseases.
Highlights
We focus here on cardiomyocytes derived from Human embryonic stem cells (hESCs) and human-induced pluripotent stem cells (hiPSCs), which are predominantly used for tissue engineering
In [83], Shum et al demonstrated that hiPSC-CMs on micropatterned anisotropic sheets diplayed drug-induced arrhythmogenicity, which could not be visualized in regular 2D cultures
The maximum size of a tissue is limited to 100–150 μm by the maximum diffusion length. This has motivated strategies to promote the formation of blood vessels precursors in engineered tissues: the addition of fibroblasts and endothelial cells or human umbilical vein endothelial cells (HUVEC) improved the formation of blood vessels precursors [73,74]; decellularized extracellular matrix (ECM) presents an already formed and mature network that can be integrated into the host vasculature when implanted [109]; and the addition of angiogenic factors was shown to improve vascularization of engineered cardiac constructs [133,134,135]
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Animal models are the most common models for cardiomyopathies [13] but have inherent limitations to recapitulate complex human physiopathology as well as inter-patient genetic variability [14,15]. Biomedicines 2021, 9, 563 and better reproduce the features of human cardiac tissues [18,19]. These 3D multicellular structures are called cardiac organoids and recapitulate at least one organ function. Different types of organoids have been developed with diverse compositions and architectures in order to reproduce the organization of the native myocardium These different geometries can lead to various readouts and applications: 3D-engineered cardiac tissues can be used to study the mechanisms involved in diseases and to test therapies. This review presents various facets of the construction of human cardiac 3D constructs from the choice of components to their patterning, the final geometry of generated tissues, and the subsequent readouts and applications to model and treat cardiomyopathies
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