Performance of a multilayered small-diameter vascular scaffold dual-loaded with VEGF and PDGF

The urgent needs of functional arterial replacements for curing the vascular system diseases have been proposed for many years. However, an ideal small-diameter vascular scaffold, which is nonthrombogenic, minimizes intimal hyperplasia, matches the mechanical properties of natural vessels, and supports neovascular tissue reconstruction, is still in progress. For this purpose, we previously attempted dual-delivery of VEGF and PDGF by double-layered electrospun membranes. Here, a multilayered vascular scaffold in 1.5-mm diameter with sufficient mechanical properties was developed by electrospinning from poly(ethylene glycol)-b-poly(L-lactide-co-ε-caprolactone) (PELCL), poly(L-lactide-co-glycolide) (PLGA), poly(ε-caprolactone) (PCL) and gelatin. Spatio-temporal releases of vascular endothelial growth factor (VEGF) and platelet-derived growth factor-bb (PDGF) were specially controlled by the inner PELCL and middle PLGA layers, respectively, and the outer PCL layer contributed to the mechanical stability. Introduction of gelatin improved vascular endothelial cells adhesion at first, and loosen membrane after its degradation facilitated vascular smooth muscle cells (VSMCs) ingrowth. Cell activities indicated dual release of growth factors promoted endothelialization and inhibited VSMCs hyperproliferation. The small-diameter vascular scaffold dual-loading VEGF and PDGF could maintain patency in rabbit left common carotid artery for 8 weeks. It is concluded that the specially prepared fibrous scaffold in multilayer could benefit blood vessel reconstruction.