Statement of Purpose: 3D cardiac microtissues developed from human induced pluripotent stem cells (hiPSC-µCTs) have offered a unique opportunity to study mechanical-induced cardiac adaptation and malfunctions. Optimal mechanical load was critical for the maintenance and maturation of hiPSC-µCTs with highly organized sarcomeres. In contrast, combination of mechanical overload and genetic deficiency has been shown to induce contractile deficits of the hiPSC-µCTs
. These studies indicated that the mechanical stress incorporates key niche elements that regulates of physiological functions and pathological phenotypes of hiPSC-µCTs. The majority of current engineered hiPSC-µCTs still heavily focus on biomimetic designs to create physiological relevant tissue models. In this study, we established a 3D cardiac tissue model based on synthetic filamentous matrices with fully artificial designs that present complex mechanical environment to the hiPSC-µCTs. In the filamentous matrices, synthetic fibers served as not only the backbone to organize a 3D cardiac microtissue, but also the physical cues to modulate the tissue mechanics. By positioning fibers with different diameters within one matrix, we created different designs of mechanical hybrid matrices, thus we can investigate the contractile behaviors and adaptive ability of hiPSC-µCTs to the complex mechanical environments.