Surface Functionalization of Electrospun Scaffolds by QK-AG73 Peptide for Enhanced Interaction with Vascular Endothelial Cells

Abstract

Rapid endothelialization still remains challenging for blood-contacting biomaterials, especially for long-term, functional, small-diameter vascular grafts. The vascular endothelial growth factor (VEGF)-mimicking QK peptide holds great promise in promoting vascular endothelial cellular activities such as adhesion, spreading, proliferation, and migration. Syndecans are transmembrane proteoglycans that are highly expressed on cell surfaces, including vascular endothelial cells, which can act as docking receptors to provide binding sites for a variety of cellular growth and signaling molecules. Herein, a novel peptide QK-AG73 that coupled the QK domain with the syndecan binding peptide AG73 was proposed, aiming to synergistically enhance the interaction with vascular endothelial cells. In addition, mechanically matched bioactive scaffolds based on poly(L-lactide-co-εcaprolactone) were successfully prepared by surface functionalization of the covalently combined QK-AG73 peptide. The result showed that the adhesion of human umbilical vein endothelial cells (HUVECs) was increased by approximately 2-fold on QK-AG73-modified surface compared with those modified with a single QK or AG73 peptide. Moreover, surface functionalization of electrospun scaffolds by this QK-AG73 peptide was more efficient in specifically promoting the proliferation of HUVECs and allowing them to grow with an elongated cobblestone-like cell morphology. It was hypothesized that both VEGF receptors and transmembrane syndecan receptors were involved in cellular regulation by the QK-AG73 peptide, which resulted in synergistic improvement of the interactions with vascular endothelial cells and provided a promising strategy to promote endothelialization of small-diameter vascular grafts.