Advances and Prospects of Cardiac Organoids in Drug Development

Cardiovascular diseases (CVDs) are the leading cause of death globally, propelling the urgent need for more effective drug development strategies. Traditional methods, such as two-dimensional (2D) cell cultures and animal models, fall short due to their limited structural complexity, lack of physiological relevance, and variations across species. These shortcomings hinder their ability to accurately predict human cardiac responses to therapeutic agents. Recently, advanced three-dimensional (3D) cardiac models, including cardiac organoids, multicellular microtissues, engineered heart tissues, and organ-on-chip platforms, have emerged as promising tools to address these limitations. This review summarizes recent advances in 3D cardiac in vitro modeling technologies, outlines major cardiac model construction strategies and their technical characteristics, and discusses their applications in drug toxicity evaluation, high-throughput drug screening, disease modeling, and personalized medicine. In addition, current challenges associated with these systems are discussed, along with future perspectives for improving their physiological relevance, scalability, and translational potential in cardiovascular drug development and precision medicine.