Viable tissue-engineering small-diameter vascular grafts should support rapid growth of an endothelial cell layer and exhibit long-term antithrombogenic property. In this study, multiple layers of various bioactive molecules, such as vascular endothelial growth factor (VEGF) and heparin, on an electrospun polycaprolactone scaffold have been developed through repeated electrostatic adsorption self-assembly (up to 20 layers), followed by genipin cross-linking. Programmed and sustained release of biomolecules embedded within the multilayered structure can be triggered by matrix metallopeptidase 2 enzyme in vitro. The result is an early and full release of VEGF to promote rapid endothelialization on the intended vascular grafts, followed by a gradual but sustained release of heparin for long-term anticoagulation and antithrombogenicity. This method of forming a biologically responsive, multimodal delivery of VEGF and heparin is highly suitable for all hydrophobic surfaces and provides a promising way to meet the critical requirements of engineered small-diameter vascular grafts.
Keywords: angiogenesis; antithrombogenicity; endothelialization; programmed and sustained drug release; surface functionalization.