Bioengineered 3D Cardiac Tissue Model for Cardiotoxicity Studies

Bioengineered 3D cardiac tissue models have the potential to revolutionize the way chemical toxicity is assessed. These models are often engineered using human-derived cells, such as stem cells, which are differentiated into heart muscle cells and assembled into a three-dimensional structure. Integrating different cell typologies (endothelial cells, fibroblasts) improves stem cell-derived cardiomyocyte maturation [1]. Bioengineered 3D cardiac tissue models could mimic a human heart's spatial and cellular organization, providing a more accurate and reliable tool for testing the effects of chemicals on the heart. Our work compares the result of a co-culture of hiPSC-CMs (80%) and HCAECs (20%) embedded in a 3D gel network based on photo-crosslinked gelatin methacryloyl (GelMA) with respect to the gold-standard 2D hiPSC-CMs culture treated with Doxorubicin 2uM. GelMA was synthesized with a 100% degree of methacryloylation, sterilized with EtO, solubilized in a cell culture medium, and photo-crosslinked upon cell encapsulation at 365 nm in the presence of a catalytic amount of photo-initiator. Chemical and rheological characterization was performed to assess synthesis success and investigate hydrogel properties. Cells were cultured for 7 days and then treated for another 7 days with Doxorubicin. At the end of 14 days, several cell functions (mitochondrial function, oxidative stress, cell integrity, cardiac, and specific cell markers) were analyzed to observe their modulation in the different in vitro systems. The results show, in the 3D culture, an increase in mitochondrial function and a reduction of the release of ROS, LDH, and high-sensitive Troponin I, providing evidence of a more resistant phenotype of the bioengineered model than the 2D system, confirming data of literature [2].