Biomimetic Hydrogel Scaffolds with Programmable Anisotropic Morphology and Conductivity for Cardiomyocyte Orientation and Maturation

ABSTRACT Development of hydrogel scaffolds with anisotropic morphology and conductivity for cardiac tissue engineering represents an extremely challenging yet highly desirable objective. While current anisotropic strategies generally satisfy the need for parallel orientation of the myocardium, simulating other specific orientations in different parts of the heart still remains a great challenge. Here, biomimetic hydrogel scaffolds with programmable anisotropic morphology and conductivity are developed by an electrode morphology‐regulated dielectrophoresis approach for cardiomyocyte orientation and maturation. By designing the electrode configuration (rectangular, triangular, and hybrid electrode), the alignment of CNTs are precisely regulated within polyisocyanopeptide (PIC) matrices: hydrogels with rectangular electrodes exhibit planar anisotropy, those with triangular electrodes reveal arcuate anisotropy, and hydrogels with a combination of triangular and rectangular electrodes result in a radial anisotropy, which is corresponding to the myofiber bundles in the central region, the periphery and the apex, respectively. These scaffolds exhibit enhanced anisotropic electrical conductivity, with higher longitudinal than transverse conductivity, promoting unidirectional electrical signal propagation and improving cardiomyocyte alignment and maturation. This strategy offers a scalable and controllable platform for preparing programmable anisotropic hydrogels to precisely simulate the region‐specific ailment of the cardiac tissue, advancing opportunities in cardiac tissue engineering and regenerative medicine.