Biomimetic Model for Electromagnetic Modulation of Cardiovascular Cellular Interactions On-Chip

Cardiovascular diseases are the leading cause of global mortality. These conditions are associated with cardiac cell death and loss of vascularization, potentially progressing to fatal myocardial infarction. However, the lack of accurate models to simulate the complex cardiac tissue microenvironment and explore alternative therapeutics contributes to heart disease still being regarded as irreversible. In this work, we developed a unique organ-on-chip platform that integrates electrical, magnetic, and mechanical stimulation to replicate the cardiac microenvironment and investigate the impact of electrical and magnetic stimulation on cardiac cell fate. Our micromodel integrated triple stimulating inputs using hybrid stimuli-responsive materials. Electromagnetic scaffolds were obtained by coating with conductive poly(3,4-ethylenedioxythiophene) polystyrenesulfonate (PEDOT:PSS) electrospun coaxial fibers comprising a polycaprolactone (PCL) shell and a core of gelatin embedded with iron oxide nanoparticles (MNPs). These scaffolds were incorporated in the chip, and the properties and biological effects of these aligned electromagnetic fibers were compared with those of PEDOT:PSS-coated gelatin hydrogels with aligned magnetic particles. In the presence of an external magnetic field, both materials became more hydrophilic. PEDOT:PSS coaxial fibers demonstrated higher electroconductivity (7.9 S·cm^-1) than the conductive hydrogels (0.83 S·cm^-1). Induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) were successfully cultured on the PEDOT:PSS coaxial fibers, as shown by cell metabolic activity assays over 8 days. Additionally, a 24-h of electric and magnetic combined stimulation significantly enhanced cell viability, with viable cell area increasing from 21% (control) to 54% in the stimulated condition. As proof of concept, we cocultured iPSC-CMs and human vascular endothelial cells (HUVECs) on the materials. Cardiac contraction, which ceased after seeding on the scaffolds, was restored through combined electric and magnetic stimulation and HUVEC culture on-chip. This approach modulates cardiac cell mechanotransduction and offers insights for modeling cardiac tissue, opening future avenues in cardiac repair and remodeling.