In vitro approaches to mimic cardiac mechanical load dynamics for enhancing maturation and disease modelling

The use of human pluripotent stem cells in cardiac tissue engineering has led to significant advances in the development of in vitro models of the human heart. However, full maturation of human pluripotent stem cell-derived cardiomyocytes has not been achieved. Current maturation strategies aim to replicate the native cardiac environment by incorporating the passive and active mechanical cues of the heart. Cardiac preload and afterload are key active mechanical loads that directly influence cardiomyocyte maturation and overall cardiac function. In this review, we explore the role of mechanical stimuli in cardiac development and cardiomyocyte maturation, with a focus on how preload and afterload dynamics can be replicated in vitro using platforms such as engineered heart tissues, stretchable membranes, bioactuators, engineered cardiac chambers, and microtissues. Additionally, we highlight the role of stimulation parameters used in dynamic preload modelling and how the incorporation of these active mechanical loads is applied in disease modelling.