Integrated effects of matrix mechanics and vascular endothelial growth factor (VEGF) on capillary sprouting

Angiogenesis is the growth of new capillaries from existing vasculature. Vascular network formation is known to be regulated by the biophysical and biochemical signals emanating from the microenvironment. However, it is not clear how endothelial cells integrate these signals to drive the capillary morphogenesis. In this study, human umbilical endothelial cells (HUVECs) were seeded on scaffolds with varying stiffness and capillary formation was quantified. Our study revealed that cells formed well defined networks on compliant gels. Increase in stiffness resulted in a decrease in sprouting. VEGF was encapsulated within the scaffolds at concentrations ranging from 0 to 100 ng/mL to investigate the interplay between VEGF concentration profiles and matrix stiffness in guiding network formation. Quantitative analysis revealed that while VEGF disrupted sprout formation on compliant substrates, it elicited a sprouting response in cells seeded on scaffolds of intermediate rigidity. Additionally, we also observed that a minimum cell density is required for the formation of well-connected vascular networks.