3D-printed nanoengineered bioadhesive with tunable stiffness for uncovering electromechanotherapy-assisted cardiac...

Fabricating anisotropic multifunctional bioadhesive patches with tunable mechanical stiffness, conductivity, antimicrobial activity, and modulating cellular behavior is crucial for successfully managing cardiac tissue injury and boosting immunogenic microenvironments. Inspired by the native myocardium, we developed a 3D printable, anisotropic, and bioadhesive cardiac patch with tunable stiffness by incorporating conductive nanofillers (GO@ND) into a biocompatible hydrogel (CSA) for regulating cardiomyogenic cues. Incorporating GO@ND enhanced the conductivity with high interfacial toughness (>250 MJ m^-1) and improved the printability with concentration-dependent self-assembly into the CSA matrix. Moreover, the electromechanical study revealed that CSA with higher stiffness (∼6.2 kPa) activated cytoplasmic YAPs during macrophage polarization and exhibited strong antibacterial efficacy. Besides, the stiffness and bioelectrical stimulation regulated human cardiomyocyte differentiation through anisotropic force-driven mechanosensors, triggering the phosphorylation of NFATc3 and activating Lamin A/C in a YAP-dependent manner. In the rat myocardial infraction (MI) model, the nanoengineered patch significantly reduced fibrosis, repaired the myocardium, and enhanced cardiac function. Based on these findings, we anticipated that the 3D-printed nanoengineered patch had tremendous potential for regulating the cardiac microenvironment with multifunctional abilities.