Abstract
The biomimetic construction of a microstructural-mechanical-electrical anisotropic microenvironment adaptive to the native cardiac tissue is essential to repair myocardial infarction (MI). Inspired by the 3D anisotropic characteristic of the natural fish swim bladder (FSB), a novel flexible, anisotropic, and conductive hydrogel was developed for tissue-specific adaptation to the anisotropic structural, conductive, and mechanical features of the native cardiac extracellular matrix. The results revealed that the originally stiff, homogeneous FSB film was tailored to a highly flexible anisotropic hydrogel, enabling its potential as a functional engineered cardiac patch (ECP). In vitro and in vivo experiments demonstrated the enhanced electrophysiological activity, maturation, elongation, and orientation of cardiomyocytes (CMs), and marked MI repair performance with reduced CM apoptosis and myocardial fibrosis, thereby promoting cell retention, myogenesis, and vascularization, as well as improving electrical integration. Our findings offer a potential strategy for functional ECP and provides a novel strategy to bionically simulate the complex cardiac repair environment.