A novel cell injection and tissue generation concept relying on spheroids is described. Hydrostatic flow transports and accumulates individual spheroids, formed from human induced pluripotent stem cell (hiPSC)-derived human cardiomyocytes, in tubular bone-shaped tissue chambers, and organoids subsequently merge to an aligned beating cardiac microtissue inside the microfluidic system. Furthermore, methods for electrical stimulation are described and in situ determination of oxygen partial pressures is enabled by optical oxygen sensor spots integrated into the microfluidic systems. A proof-of-concept demonstrating electrical stimulation combined with in situ monitoring of metabolic activity in cardiac tissues is provided. The developed system can be considered a versatile platform enabling e.g., the investigation of the effect of administered drugs on oxygen consumption of physiological microtissue.
Fusing spheroids to aligned μ-tissues in a heart-on-chip featuring oxygen sensing and electrical pacing capabilities
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