Tissue engineering is an exciting multi-disciplinary field aimed at creating three-dimensional surrogates for nearly every tissue in the body. This is accomplished by combining living cells with material scaffolds and biologically active molecules, which are then cultured in specially designed bioreactors that mimic key aspects of the in vivo niche environment.

Originally intended to develop fully functional biomaterials for surgical replacement of damaged body parts that cannot regenerate, increasingly sophisticated 3D-engineered tissues have also become powerful tools for in vitro studies ranging from fundamental biology to disease modeling and therapeutic screening applications in the laboratory. Cardiac tissue engineering is particularly challenging because heart muscle cells from patient biopsies have very limited availability and can neither survive nor proliferate in culture. However, the Nobel Prize-winning discovery of induced pluripotent stem cells (iPSCs) now provides virtually unlimited supplies of nearly any cell type, including cardiomyocytes and other cardiovascular cells. An additional advantage of using iPSCs is that the resulting cells and tissues are genetically matched to the original donor, providing further opportunities for developing personalized engineered tissues for precision medicine applications.

Capitalizing on Mount Sinai’s world-renowned expertise in human pluripotent stem cell biology, Cardiovascular Research Institute (CVRI) investigators have been pushing the boundaries of human cardiac tissue engineering for over a decade. We were one of the first in the world to develop human engineered cardiac tissue (hECT) and to perform rigorous validation comparing hECT to native human heart muscle physiology [1]. We were the first to develop a hECT model of hypertrophic cardiomyopathy using iPSCs from patients with an inherited genetic disorder characterized by aberrant signaling in the RAS/MAPK signaling cascade (RASopathy) [2]. Addtionally, we were the first to engineer a pumping human mini-heart chamber that can generate pressure and eject fluid, yielding pressure-volume measurements of ventricular function such as ejection fraction, cardiac output, and stroke work that are immediately familiar to clinical cardiologists [3]. We have developed new bioreactor technologies to improve hECT biofidelity, longevity, throughput, and ease of use for a wide range of applications [4]. Currently, in collaboration with an international team of investigators funded by a Transatlantic Network of Excellence grant from the Fondation Leducq, our team is employing patient-specific hECTs to seek a cure for a rare but severe form of familial heart disease related to phospholamban gene mutations [5]. We are also pioneering new advances in microphysiologic systems by combining microfluidic chips and micro-scale tissue engineering to create tube-like cardiovascular organoids that integrate multiple perfusable tissue types with a heart-driven pulsatile fluid flow. These microfluidic cardiovascular chips are being used to study early stages of human heart development. Additional applications include evaluating accelerated cardiovascular aging due to microgravity on the International Space Station, measuring human-specific cardiovascular risks of space-type radiation, and developing effective countermeasures to help ensure astronaut safety during long-term exploratory space missions.