Abstract
The goal of therapeutic angiogenesis is the development of functional and mature vasculature by combining biological and physical cues that mimic the native extracellular matrix. In this study we evaluated if immobilizing vascular endothelial growth factor (VEGF) gradients and SDF-1α on gelatin nanofibrous scaffolds with different fiber orientations (i.e. random or aligned) influence the angiogenic potential of endothelial progenitor cells (EPCs) and human umbilical vein endothelial cells (HUVECs). Both cell types successfully adhered onto gelatin B scaffolds. VEGF gradients alone or combined with SDF-1α as well as fiber orientation had a pronounced effect on cell behavior, morphology and orientation. Cells organized themselves parallel to the fibers of the electrospun scaffolds with the aligned orientation and developed a spindle-like morphology. Conversely, cells cultured on scaffolds with random fiber orientation, did not display directionality and appeared to have a rounder shape. Cell migration and capillary formation were found to be dependent on VEGF gradients, SDF-1α presentation and cell type. These findings indicate that electrospun scaffolds are capable of regulating spatial growth factor presentation and influence cellular organization.