Acute Response of Engineered Cardiac Tissue to Pressure and Stretch

Abstract

The heart is a dynamic organ, and the cardiac tissue experiences changes in pressure and stretch during the cardiac cycle. Existing cell culture and animal models are limited in their capacity to decouple and tune specific hemodynamic stresses implicated in the development of physiological and pathophysiological cardiac tissue remodeling. This study focused on creating a system to subject engineered cardiac tissue to either pressure or stretch stimuli in isolation and the subsequent evaluation of acute tissue remodeling. We developed a cardiac tissue chip containing three-dimensional (3-D) cell-laden hydrogel constructs and cultured them within systems where we could expose them to either pressure changes or volume changes as seen in the left ventricle. Acute cellular remodeling with each condition was qualitatively and quantitatively assessed using histology, immunohistochemistry, gene expression studies, and soluble factor analysis. Using our unique model system, we isolated the effects of pressure and stretch on engineered cardiac tissue. Our results confirm that both pressure and stretch mediate acute stress responses in the engineered cardiac tissue. However, both experimental conditions elicited a similar acute phase injury response within this timeframe. This study demonstrates our ability to subject engineered cardiac tissue to either pressure or stretch stimuli in isolation, both of which elicited acute tissue remodeling responses.