Nanogrooved Elastomeric Diaphragm Arrays for Assessment of Cardiomyocytes under Synergistic Effects of Circular Mechanical Stimuli and Electrical Conductivity to Enhance Intercellular Communication.

Abstract

Cardiovascular diseases remain the leading cause of mortality, necessitating advancements in in vitro cardiac tissue engineering platforms for improved disease modeling, drug screening, and regenerative therapies. The chief challenge to recapitulating the beating behavior of cardiomyocytes is creation of the circular stress profile experienced by hollow organs in the natural heart due to filling pressure and integrated strategies for intercellular communication to promote cell-to-cell connections. We present a platform featuring addressable arrays of nanogrooved polydimethylsiloxane (PDMS) diaphragms for cell alignment and circular mechanical stimulation, with embedded silver nanowires (AgNWs) for electrical cues, so that cardiomyocyte functionality can be assessed under these synergistic influences. Central to our innovation is a two-layer PDMS diaphragm design that electrically isolates the liquid metal (EGaIn) strain sensor in the bottom layer to enable detection and control of mechanical stimulation from conductive portions of embedded AgNWs in the top layer that supports cardiomyocyte culture and communication. In this manner, through localized detection and control of the circular mechanical stimulation, the essential role of multiaxial stretching on cardiomyocyte function is elucidated based on their contractility, sarcomere length, and connexin-43 expression. This in vitro platform can potentially transform cardiac tissue engineering, drug screening, and precision medicine approaches.