Gold Nanorods in Cardiac Millitissues: Assessing Mechanical and Contractile Dynamics in a Living Engineering Myocardium Model

ABSTRACT The active mechanical properties of cellular cardiac millitissue and the corresponding mechano‐electro‐contractility relationship remain unexplored. This study aims to bridge these knowledge gaps by examining the active mechanical and full‐field contractile properties of living cardiac millitissues with and without gold nanorods (GNRs). To achieve that, a novel nanoindentation setup equipped with temperature control and dual‐camera systems is employed to capture the dynamic mechanical properties of these tissues. The mechanical results delineate the multiphasic nature of tissue maturation and organization, ascribing to the role of GNRs in strengthening the structural network, modulating cellular behaviors, and enhancing electrical conductivity. Additionally, this advanced mechanical testing setup, together with full‐field contractile profiles, uniquely captures localized contractility properties and reveals the localized functions of GNRs in cell–cell communication and electrophysiological behaviors. These findings elucidate the mechano‐electro‐conductivity relationship: electrical properties of millitissues integrated with GNRs significantly affect their active mechanobiological responses. Additionally, our data indicates that integrating nanomaterials substantially influences two structural aspects: (1) localized structural reorganization, (2) accelerated tissue remodeling rate, which are additional benefits in promoting millitissue maturity compared to the electrical stimulation method. Overall, this study establishes a foundational platform for future exploration of the mechanoelectrical coupling in cardiac millitissues.