Engineering and Assessing Cardiac Tissue Complexity

Abstract

Cardiac tissue engineering is very much in a current focus of regenerative medicine research as it represents a promising strategy for cardiac disease modelling, cardiotoxicity testing and cardiovascular repair. Advances in this field over the last two decades have enabled the generation of human engineered cardiac tissue constructs with progressively increased functional capabilities. However, reproducing tissue-like properties is still a pending issue, as constructs generated to date remain immature relative to native adult heart. Moreover, there is a high degree of heterogeneity in the methodologies used to assess the functionality and cardiac maturation state of engineered cardiac tissue constructs, which further complicates the comparison of constructs generated in different ways. Here, we present an overview of the general approaches developed to generate functional cardiac tissues, discussing the different cell sources, biomaterials, and types of engineering strategies utilized to date. Moreover, we discuss the main functional assays used to evaluate the cardiac maturation state of the constructs, both at the cellular and the tissue levels. We trust that researchers interested in developing engineered cardiac tissue constructs will find the information reviewed here useful. Furthermore, we believe that providing a unified framework for comparison will further the development of human engineered cardiac tissue constructs displaying the specific properties best suited for each particular application.

A Conductive Bioengineered Cardiac Patch for Myocardial Infarction Treatment by Improving Tissue Electrical Integrity

“…[29] The application of ES is effective in obtaining highly mature ECT constructs as it promotes cell growth, orientation, and/or maturation. [30] The Vunjak-Novakovic lab was the first to apply ES to Ultrafoam Collagen Sponges cultured with neonatal rat CMs, culturing them under 1 Hz electrical pulses for 8 days to construct engineered myocardial tissue. [31] To enhance the role of ES, we further studied the effect of conductive SP50 combined with ES.…”

Advances in Cardiac Tissue Engineering

“…Both ESC-derived and iPSC-derived CM are also more structurally similar to neonatal cells than adult CM, hindering applications of hCMPs composed of immature iPSC-derived CM. However, clusters of other cell types (e.g., progenitor cells and spheroids) have also been incorporated into the heart patch and evaluated in preclinical models of myocardial injury [ 9 ]. It is also important to note how Zhao et al is working on differentiating muscle cells into specific ventricular and atrial cells [ 9 ].…”

“…However, clusters of other cell types (e.g., progenitor cells and spheroids) have also been incorporated into the heart patch and evaluated in preclinical models of myocardial injury [ 9 ]. It is also important to note how Zhao et al is working on differentiating muscle cells into specific ventricular and atrial cells [ 9 ].…”

Human Induced Pluripotent Stem Cell as a Disease Modeling and Drug Development Platform—A Cardiac Perspective

“…Further, many studies focus on vascularization of the cardiac organoids to overcome the lack of oxygen and nutrient diffusion, by coating the organoids with an extracellular matrix containing endothelial cells [ 297 ], cultured cardiac organoids with hPSC-derived endothelial cells [ 298 ], and fusion of two subregional organoids to form a complete organ [ 299 ]. Moreover, cardiac tissue engineering field has rapidly evolved over the past decade and offers a biomedicine discipline attempting to combine scaffolding polymers with cardiovascular cells to create cardiac tissue-like structures for drug screening, disease modeling, and cardiac repair [ 300 , 301 , 302 , 303 , 304 , 305 ]. Interestingly, the use of heart-on-a-chip models has recently increased, providing a controllable tool, mean oxygen delivery [ 306 , 307 , 308 , 309 ], pH [ 308 ], shear stress with a certain flow rate of the culture medium [ 310 , 311 ], temperature control, and electrical or mechanical stimulation, as well as continuous monitoring and measurement of parameters of the physiological responses of the cells.…”