Tissue-Engineering for the Study of Cardiac Biomechanics

Abstract

The notion that both adaptive and maladaptive cardiac remodeling occurs in response to mechanical loading has informed recent progress in cardiac tissue engineering. Today, human cardiac tissues engineered in vitro offer complementary knowledge to that currently provided by animal models, with profound implications to personalized medicine. We review here recent advances in the understanding of the roles of mechanical signals in normal and pathological cardiac function, and their application in clinical translation of tissue engineering strategies to regenerative medicine and in vitro study of disease.

Increased Afterload Augments Sunitinib-Induced Cardiotoxicity in an Engineered Cardiac Microtissue Model

“…Animal models do not allow for precise control over biomechanical and biochemical factors (31) . Likewise, the use of 2D cell cultures also suffers from serious shortcomings, such as inability to apply mechanical pre-load and afterload, which are essential features of cardiac physiology (32) . Taking advantage of recent advances in tissue engineering, we created 3D CMT that better mimic in vivo conditions without sacrificing control over cellular, biochemical, and mechanical inputs.…”

Anisotropic engineered heart tissue made from laser-cut decellularized myocardium

“…In conclusion, our method for generating artificial cardiac tissue joins several others that have been developed in recent years (reviewed elsewhere47). Evaluating the utility of any given approach depends as much on the intended use of the EHT as it does on any particular metric of performance.…”

“…There is a large and diverse body of methods for the generation of engineered heart tissue, each one with benefits for specific applications 4 7 . In evaluating our approach, it is useful to draw some comparisions with other methods.…”

“…These can include gene mutations, endocrine factors, and mechanical loads applied to the tissue 2 . Engineered heart tissues (EHTs) could be transformative in vitro tools for studying the remodeling process, because they allow the various contributing factors to be manipulated systematically in a controlled environment 3 4 5 6 7 .…”

Fitting tissue chips and microphysiological systems into the grand scheme of medicine, biology, pharmacology, and toxicology

“…A much more comprehensive battery of techniques is already in regular use in the pharmaceutical industry, including genomics, transcriptomics, and proteomics. In recent MPS studies, we are seeing functional measurements such as contractility, calcium signaling, and electrophysiological responses of cardiac and skeletal muscle, 37,[69][70][71][72][73][74][75] electrical resistance and molecular permeability of barriers, [76][77][78][79][80][81][82] and metabolomic responses to inflammatory challenges. 78 In this issue, the Parker group uses a variety of measures, including gene expression profiling, to quantify factors that affect maturation of neonatal rat cardiomyocytes into a more mature phenotype.…”