Angiogenic Potential of Endothelial Cells in Response to the Stiffness and Anisotropy of Right Ventricle Mimetic Scaffolds.

Right ventricular (RV) failure secondary to pulmonary hypertension manifests in significant biomechanical alterations of myocardial tissue, including capillary rarefaction and enhanced stiffness and anisotropy. However, how the changes in mechanical cues affect the angiogenic potential of endothelial cells (ECs)-and thereby impact the RV failure progression-remains unclear. The aim of this study is to investigate the effects of RV-relevant substrate stiffness and anisotropy on different EC types using polyurethane urea scaffolds engineered to mimic RV tissues. We find that substrate anisotropy increased EC number but reduced metabolic activity in both cell types. In contrast, the two cell types exhibit divergent responses in their angiogenic potential and angiogenic protein secretome. For HUVECs, neovessel formation is suppressed by substrate stiffening and anisotropy, whereas for HCMECs, it is increased by stiffening and suppressed by anisotropy. Our results highlight the mechanobiological regulation of ECs in a tissue- and cell-type-dependent manner, which is critical for new biomaterial or in vitro model development for cardiac diseases.