Recapitulating Cardiac Structure and Function In Vitro from Simple to Complex Engineering

Abstract

Cardiac tissue engineering aims to generate in vivo-like functional tissue for the study of cardiac development, homeostasis, and regeneration. Since the heart is composed of various types of cells and extracellular matrix with a specific microenvironment, the fabrication of cardiac tissue in vitro requires integrating technologies of cardiac cells, biomaterials, fabrication, and computational modeling to model the complexity of heart tissue. Here, we review the recent progress of engineering techniques from simple to complex for fabricating matured cardiac tissue in vitro. Advancements in cardiomyocytes, extracellular matrix, geometry, and computational modeling will be discussed based on a technology perspective and their use for preparation of functional cardiac tissue. Since the heart is a very complex system at multiscale levels, an understanding of each technique and their interactions would be highly beneficial to the development of a fully functional heart in cardiac tissue engineering.

Quantitative Evaluation of Cardiac Cell Interactions and Responses to Cyclic Strain

“…In the ventricles of the human heart, there is approximately twice the amount of cardiomyocytes when compared to fibroblasts [1][2][3]55]. However, the familiar organization found in healthy heart tissue did not appear until cardiomyocytes occupied approximately 80% of the culture in vitro (Figure 2I fractions > 0.8) [7][8][9]. One of the possible reasons for the difference observed in the cellular composition in vitro is that the heart has a laminar hierarchy, which consists of layers or "sheets" of muscle a few myocytes thick connected by collagen fibers [56][57][58].…”

“…The two dominant cell types in the myocardium are cardiomyocytes and cardiac fibroblasts; cardiomyocytes generate contractile force [1][2][3], while fibroblasts play vital roles in maintaining functions within the heart, such as extracellular matrix production, cardiac remodeling, cell-cell signaling, promoting blood vessel formation, and secretion of growth factors and cytokines [4][5][6]. In a healthy heart, cardiomyocytes and fibroblasts are organized along the direction of contraction [7][8][9]. However, in the event of myocardial infarction or other cardiac diseases, there is increased migration of fibroblasts into the regions of damaged tissue as well as changes to the morphology and viability of the myocytes [10][11][12][13][14][15].…”

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

“…[ 23 ] Using this technique, a vast number of cardiac cells that can grow in three dimensions are introduced, and thick functional engineered myocardial tissues are generated through electromechanical stimulation in vitro. [ 24 ] These artificial myocardia not only have some of the functions of mature myocardium (rhythmic electrical signals, gap junction structure, etc.) but could also generate electromechanical coupling with the host to better restore the damaged heart.…”

Recent advances in soluble decellularized extracellular matrix for heart tissue engineering and organ modeling

“…The myocardial microenvironment plays a vital role in the multitude of biological processes and regulating cellular behavior. 41,220,221 Therefore, engineered constructs with controlled architectures and micro/ nanoscale patterns can mimic the anisotropic nature of the myocardium and promote the alignment and maturation of cardiac cells. 222 In this direction, soft lithography has provided a promising tool to fabricate micro/nanoscale anisotropic engineered cardiac tissue.…”