Bioreactor for the formation and maturation of human cardiac constructs. (A, B) Overview of the bioreactor. Constructs formed by seeding hiPS-CMs in a collagen–fibrinogen hydrogel around flexible pillars. Flexible pillars provided mechanical conditioning through passive tension and allowing for auxotonic contractions. (C–E) Immunofluorescence images demonstrating the presence of aligned and cross-striated hiPS-CMs along the edge of the construct. 4′,6-Diamidino-2-phenylindole (blue), cardiac troponin T (green/white). (F, G) Response of cardiac constructs to β-adrenergic stimulation using isoproterenol. (F) BPM for chronotropic response and (G) FAC as an indicator of force generation for ionotropic response. Data are presented as mean ± SD (n = 6). hiPS-CM, human induced pluripotent stem cell-derived cardiomyocyte; BPM, beats per minute; FAC, fractional area change; SD, standard deviation. Color images are available online.