Biofabrication of 3D cardiac spheroids via magnetic levitation guided assembly for doxorubicin-induced cardiotoxicity study

Three-dimensional (3D) cell culture offers alternative approaches to two-dimensional (2D) cell culture and animal models because it mimics the physiology and metabolism of native tissues. Magnetic levitation (MagLev) is a new and promising technique for biofabrication of 3D cardiac spheroids in a scaffold-free microenvironment. In this study, we introduce a rapid and cost-effective methodology for the fabrication of 3D cardiac spheroids to investigate doxorubicin-induced cardiotoxicity. Here, Gadobutrol (Gx) was utilized as a paramagnetic agent to magnetically assemble cardiac cells. For this purpose, initial cell density, and culture time were optimized. Then, fabricated 3D cardiac spheroids were characterized by immunostaining of cellular and extracellular components. In addition, cardiac-specific markers of cardiac troponin T and MYH6 were investigated. Further, the drug response of 3D cardiac spheroids was evaluated for doxorubicin, and IC values were obtained as 3.5 and 14.7 µM for 2D control and 3D cardiac spheroids, respectively. The acquired results emphasize that 3D cardiac spheroids are more resistant to drug exposure. Hereby, these findings indicate that biofabrication of 3D cardiac spheroids via MagLev methodology might be an alternative platform for drug screening.