3D Printed Multifunctional Bioadhesive Patch with Intrinsic Bioelectronic Properties for Decoding Electromechanical and Anisotropic Cardiac Microenvironment

Abstract

Fabricating anisotropic multifunctional bioadhesive patches with tunable mechanical stiffness, electrical conductivity, antimicrobial activity, and modulating cellular behavior is crucial for the successful management of cardiac tissue injury and boosting immunogenic microenvironments. Direct ink writing (DIW)-based 3D printing holds tremendous potential for developing electroactive cardiac patches (ECPs) with anisotropic microarchitecture. Inspired by the native myocardium, we developed a multifunctional and anisotropic ECP with tunable stiffness by incorporating a highly conductive graphene oxide/nanodiamond (GO@ND) complex into a biocompatible carboxymethyl chitosan/polyvinyl alcohol (CSA) matrix for regulating immunogenic and cardiomyogenic cues. The incorporation of GO@ND enhanced the electrical conductivity ([~]22.6 S mm-1) with high interfacial toughness (>250 MJ m-1) and improved the printability (n = 0.5) with concentration-dependent self-assembly into the CSA matrix. We observed that electrical stimulation (EFs; 250 mV/20 min/day) through nanoengineered CSA resulted in broad-spectrum antibacterial activity against E. coli and S. aureus by 99.29% and 98.74%, respectively, via sustained release of curcumin (Cur). Moreover, the electromechanical study revealed that CSA with higher stiffness ([~]6.2 kPa) activated cytoplasmic YAPs during macrophage polarization. Besides, stiffness and EFs regulated human cardiomyocyte differentiation through anisotropic force-driven early activation of Vinculin, triggering the phosphorylation of NFATc3 and activating Lamin A/C in a YAP-dependent manner. Based on these findings, we anticipated that the fabricated nanoengineered patch had tremendous potential for regulating the electro-cardiomyogenic microenvironment with multifunctional abilities.