Towards engineering heart tissues from bioprinted cardiac spheroids.

Current in vivo and in vitro models fail to accurately recapitulate the human heart microenvironment for biomedical applications. This study explores the use of cardiac spheroids (CSs) to biofabricate novel and advanced physiological cardiac models for in vitro testing. CSs were created from human cardiac myocytes, fibroblasts and endothelial cells, mixed within optimal alginate/gelatin (Al/Ge) hydrogels and then bioprinted on a microelectrode plate for drug testing. Bioprinted CSs maintained their structure and viability for at least 30 days after printing. Vascular endothelial growth factor (VEGF) promoted endothelial cell branching from CSs within hydrogels. Alginate/gelatin-based hydrogels enabled spheroids fusion, which was further facilitated by addition of VEGF. Bioprinted CSs contracted spontaneously and under stimulation, allowing to record contractile and electrical signals on the microelectrode plates for industrial applications. Taken together, our findings indicate for the first time that bioprinted CSs within Al/Ge hydrogels can be used to biofabricate durable, viable and functional human heart tissues for long term in vitro testing.