Tissue engineered models of the human heart

Abstract

Recent advancements in bioengineering have led to sophisticated in vitro models that mimic human organ functions, transforming biomedical research and reducing reliance on animal testing. Microphysiological systems (MPS), such as Engineered Heart Tissues (EHTs), recreate 3D interactions, providing a more accurate representation of human tissue than traditional 2D cultures. EHTs, made from human-induced pluripotent stem cells (hiPSCs) and extracellular matrix scaffolds, can measure heart tissue function but face challenges like high cell demands and inconsistent measurements. To address this, we miniaturized EHTs, reducing cell requirements while maintaining functional accuracy. This innovation enhances throughput in drug screening and disease modelling. Adding cell types like endothelial cells has further increased physiological relevance. Additionally, the ForceTracker tool improves contractile force measurements, and optimized EHT platform pillars ensure consistency. Our research also examined how cellular distribution and factors like TGF-β affect EHT function, particularly in cardiac fibrosis modelling. These advancements enable precise experimental control, improving disease modelling and therapeutic testing. Miniaturized EHTs represent a major step forward in cardiac research, offering a valuable alternative to animal models while advancing the understanding of disease mechanisms and treatment development.