Evaluation of CuO nanoparticle toxicity on 3D bioprinted human iPSC-derived cardiac tissues

Particulate matter has been identified as a significant environmental threat to human health. As one of its components, copper oxide nanoparticles (CuO NP) have been found highly potent in cytotoxicity. However, the elucidation of its mechanism is still limited. This study investigated the toxicity of CuO NP toward a cardiac tissue. To better recapitulate the species-specific tissue phenotype and toxin response, we developed a human induced pluripotent stem cells (iPSC)-derived cardiac micro-tissue. With the precise deposition of the cell and scaffold material enabled by rapid 3D bioprinting, the cardiac micro-tissue showed a mature phenotype and was incorporated with a force gauge to enable contraction measurement. We discovered an LD50 of 7.176 g/mL from the CuO NP treatment outcome of the micro-tissue with a downward trend in tissue force as toxicity increased. We also identified mitochondrial damage and activation of extrinsic apoptosis as a significant pathway to mediate the tissue toxicity.