High and intermittent hydrostatic pressure promotes maturation of engineered cardiac tissues derived from human pluripotent stem cells

Ventricular loading pressure plays a vital role in cardiac repair, prompting the hypothesis that hydrostatic pressure could enhance ECT maturation. ECTs were created by co-culturing hPSC-derived cardiovascular cells with extracellular matrix proteins and subjecting them to intermittent hydrostatic pressure (1 hour/day at 50 kPa for 3 days after 2 weeks of pre-culture).

This protocol improved cardiomyocyte alignment, mitochondrial content, and metabolic and functional maturation, evidenced by enhanced contractility, calcium flux, and single-cell RNA sequencing. Endothelial cells were critical for these effects, as their absence prevented maturation. Hydrostatic pressure combined with dynamic culture also promoted vascular network formation.