Cardiac diseases account for 600,000 deaths each year in America, and this number continues to climb annually. To improve survival outcomes, in vitro models to better understand cardiac diseases need to be developed. Currently, animal models are used to test therapeutics, but beyond the large expense to raise the animals, their anatomy and physiology do not fully emulate that of humans. Induced pluripotent stem cells (iPSCs) can be differentiated into any cell type to study a system of interest and are advantageous over animal models, as they can be derived from humans and used to create representative disease models.

The Ogle lab (University of Minnesota) has developed a 3D printed, chambered cardiac mimic (hChaM) using human iPSCs embedded in an extracellular matrix-based scaffold. The cells in this structure undergo differentiation to become cardiomyocytes and can also include multiple cardiac cell types, including fibroblast, pacemaker, and endothelial cells. However, iPSC-derived cardiomyocytes are currently limited by their lack of structural and functional maturity. Therefore, we aim to create a bioreactor for the hChaM, which we hypothesize will allow for increased differentiation efficiency and enhanced maturation of differentiated cells as a function of imposed mechanical strain and improved nutrient delivery. While cardiac bioreactors have previously been developed, the associated tissue mimics typically only involve one cell type and a macroscale strip of muscle, rather than a compartmentalized heart model with multiple cell types as proposed here. Additionally, we will incorporate pressure-volume (PV) sensors2, as PV loops are a common tool used in the clinical setting for analyzing cardiac function, including blood ejection and filling, stroke work, contractility, end-systolic and end-diastolic PV relations, and pump efficiency. The addition of PV sensors will allow for studies that delineate the influence of mechanistic changes on PV dynamics.

Upon completion of the bioreactor, we will use the 3D printed cardiac mimics to model a genetic cardiac disease state, familial hypertrophic cardiomyopathy (HCM). Approximately one in five hundred people suffer from familial HCM, which typically leads to arrhythmias and heart failure, and in some cases sudden cardiac death. The bioreactor will be key in replicating physiological conditions, through perfusion with a blood substitute. The resulting model will allow us the ability to understand how the genetic mutations lead to remodeling of the heart chambers and ultimately to changes in function, including PV dynamics.