Enhanced vascularization of PCL porous scaffolds through VEGF-Fc modification

Abstract

To accelerate the vascularization of engineered tissue, an endothelial-specific fusion protein (VEGF-Fc), which consists of a human vascular endothelial growth factor (VEGF) and an immunoglobulin G Fc region, was fabricated and used to construct a bioactive interface in a porous scaffold. In this study, VEGF-Fc was immobilized on polycarprolactone (PCL) porous scaffolds by steeping, which is mediated by the hydrophobic binding of the Fc domain. The VEGF-Fc proteins were distributed stably and uniformly throughout the PCL porous scaffolds without affecting their surface morphology and mechanical properties. The immobilized VEGF-Fc activated the phosphorylation of VEGF2 receptor continuously, and further promoted the expressions of PI3K and MAPK, which effectively enhanced the adhesion and proliferation of human vascular endothelial cells (HUVECs). Furthermore, the immobilized VEGF-Fc promoted the migration of HUVECs into the scaffolds, and also enhanced the cellularization and ECM deposition in the subcutaneous implanted scaffolds in rats, which synergistically supported the vascularization of the scaffold in vivo. In view of the advantages of easy use, stability and efficiency, the VEGF-Fc fusion protein appeared to be a promising candidate for surface modification of porous scaffolds for tissue engineering.