Engineering Cardiovascular Tissue Chips for Disease Modeling and Drug Screening Applications

Abstract

In recent years, the cost of drug discovery and development have been progressively increasing, but the number of drugs approved for treatment of cardiovascular diseases (CVDs) has been limited. Current in vitro models for drug development do not sufficiently ensure safety and efficacy, owing to their lack of physiological relevance. On the other hand, preclinical animal models are extremely costly and present problems of inaccuracy due to species differences. To address these limitations, tissue chips offer the opportunity to emulate physiological and pathological tissue processes in a biomimetic in vitro platform. Tissue chips enable in vitro modeling of CVDs to give mechanistic insights, and they can also be a powerful approach for drug screening applications. Here, we review recent advances in CVD modeling using tissue chips and their applications in drug screening.

Current methods for fabricating 3D cardiac engineered constructs

“…By delivering an oversimplified model of heart structure and function, these devices take advantage of induced native tissue characteristics such as multidimensional cell interactions and mimicked vasculature perfusion to model complex systems in a concise manner. These devices can be created using iPSC-derived cardiovascular cells from a healthy donor or a patient to give insight into the specific response of an individual to a given drug ( Chan and Huang, 2021 ). Other methods best suited for the creation of cardiac disease models include hydrogels, electrospinning-derived scaffolds, and 3D bioprinting.…”

Timely delivery of cardiac mmRNAs in microfluidics enhances cardiogenic programming of human pluripotent stem cells

“…The high disease burden, both immediate and chronic, imposes great costs onto healthcare systems which necessitate the development of novel therapeutic strategies ( Roth et al, 2020 ). The main issue of current pharmacological and interventional therapeutic approaches is their inability to compensate the great and irreversible loss of functional cardiomyocytes (CMs), due to the very limited supplies of cardiac cells for dedicated studies ( Chan and Huang, 2021 ).…”

Acute Response of Engineered Cardiac Tissue to Pressure and Stretch

“…Tissue chip models containing engineered cardiac tissue offer advantages in screening cardiotoxic compounds and elucidating mechanisms and signaling pathways involved in disease development [Chan and Huang, 2021]. Since alterations in intraventricular pressure and myocardial stretch play significant roles in cardiovascular disease progression, incorporating these stresses is critical when constructing cardiac tissue chips aimed at modeling different cardiovascular disease states.…”