A multi-cellular 3D bioprinting approach for vascularized heart tissue engineering based on HUVECs and iPSC-derived cardiomyocytes

Abstract

The myocardium behaves like a sophisticated orchestra that expresses its true potential only if each member performs the correct task harmonically. Recapitulating its complexity within engineered 3D functional constructs with tailored biological and mechanical properties, is one of the current scientific priorities in the field of regenerative medicine and tissue engineering. In this study, driven by the necessity of fabricating advanced model of cardiac tissue, we present an innovative approach consisting of heterogeneous, multi-cellular constructs composed of Human Umbilical Vein Endothelial Cells (HUVECs) and induced pluripotent cell-derived cardiomyocytes (iPSC-CMs). Cells were encapsulated within hydrogel strands containing alginate and PEG-Fibrinogen (PF) and extruded through a custom microfluidic printing head (MPH) that allows to precisely tailor their 3D spatial deposition, guaranteeing a high printing fidelity and resolution. We obtained a 3D cardiac tissue compose of iPSC-derived CMs with a high orientation index imposed by the different defined geometries and blood vessel-like shapes generated by HUVECs which, as demonstrated by in vivo grafting, better support the integration of the engineered cardiac tissue with host’s vasculature.

The Emergence of Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes (hiPSC-CMs) as a Platform to Model Arrhythmogenic Diseases

“…Native-like in vitro environments obtained from mixing various cell populations and suitable biomaterials may provide the means to generate a mature electrophysiological phenotype, currently lacking in 2D cultures [161,185]. 3D bioprinting currently allows the rapid fabrication of living human tissue with cardiac-like patterns using different primary cell types [186]. 3D bioprinted human cardiac tissues are expected to improve the predictive accuracy of the non-clinical drug discovery process by providing industry and researchers with the technology to create highly customized physiologically relevant 3D human tissue models (healthy and diseased) for developing new therapeutic options [187].…”

3D Bioprinting: from Benches to Translational Applications

“…As the authors were able to demonstrate the performance of their patch in vivo, it might indicate the potential of clinical translation of these 3D‐bioprinted cardiac tissues. Similarly, Maiullari et al recently bioprinted cardiac tissues composed of HUVECs and iPSC derived cardiomyocytes based on an alginate/PEG‐fibrinogen bioink . Their 3D cardiac tissues showed high cell alignment as well as the formation of blood vessels, which upon in vivo implementation into nonobese diabetic SCID mice showed high integration with the host vasculature, proving the functionality of their bioprinted cardiac tissues.…”

3D Bioprinting in Skeletal Muscle Tissue Engineering

“…In the future, the use of stimuli‐responsive hydrogels in bioprinting may contribute to the development of smart bioinks . Furthermore, despite being reported in different studies, multimaterial and multicellular bioprinting has been scarcely explored due to the complexity of the printer setup that generally does not allow precise cell compartmentalization . Natural tissues, such as skeletal muscle tissue, have complex multicellular anisotropic structure in relation with the nervous and vascular networks.…”