Mussel-Inspired Immobilization of Vascular Endothelial Growth Factor (VEGF) for Enhanced Endothelialization of Vascular Grafts

Abstract

Most polymeric vascular prosthetic materials have low patency rate for replacement of small diameter vessels (<5 mm), mainly due to failure to generate healthy endothelium. In this study, we present polydopamine-mediated immobilization of growth factors on the surface of polymeric materials as a versatile tool to modify surface characteristics of vascular grafts potentially for accelerated endothelialization. Polydopamine was deposited on the surface of biocompatible poly(L-lactide-co-ε-caprolactone) (PLCL) elastomer, on which vascular endothelial growth factor (VEGF) was subsequently immobilized by simple dipping. Surface characteristics and composition were investigated by using scanning electron microscopy, atomic force microscopy, and X-ray photoelectron spectroscopy. Immobilization of VEGF on the polydopamine-deposited PLCL films was effective (19.8 ± 0.4 and 197.4 ± 19.7 ng/cm(2) for DPv20 and DPv200 films, respectively), and biotin-mediated labeling of immobilized VEGF revealed that the fluorescence intensity increased as a function of the concentration of VEGF solution. The effect of VEGF on adhesion of HUVECs was marginal, which may have been masked by polydopamine layer that also enhanced cell adhesion. However, VEGF-immobilized substrate significantly enhanced proliferation of HUVECs for over 7 days of in vitro culture and also improved their migration. In addition, immobilized VEGF supported robust cell to cell interactions with strong expression of CD 31 marker. The same process was effective for immobilization of basic fibroblast growth factor, demonstrating the robustness of polydopamine layer for secondary ligation of growth factors as a simple and novel surface modification strategy for vascular graft materials.

Effect of fibroin sponge coating on in vivo performance of knitted silk small diameter vascular grafts

“…They are serious problems especially for small diameter artificial vascular grafts. [22][23][24][25][26] To improve graft patency, thrombus formation and neointimal hyperplasia should be controlled. Early stage endothelialisation offers a potential solution.…”

Multifunctional MgF2/Polydopamine Coating on Mg Alloy for Vascular Stent Application

“…As a simple, versatile, and effective strategy to promote cell adhesion onto substrates with various material type and shape under solvent-free and non-toxic condition, polydopamine (PDA) films has attracted much attention in the field of biomaterials surface modification since Lee et al reported it in 2007 [41] . In the field of vascular biomaterials, PDA coating has been used as an immobilization layer for vascular endothelial growth factor (VEGF) [42,43] , heparin [44,45] , etc., and has also been used to control cell behaviors directly on the surface, which demonstrated that human umbilical vein endothelial cells (HUVECs) could adhere well and spread with a high viability on PDA coating [46][47][48] ; moreover, it showed that PDA coating on 316L stainless steel stent decreased adhesion and proliferation [48] .…”

Strategies and Techniques to Enhance theIn SituEndothelialization of Small-Diameter Biodegradable Polymeric Vascular Grafts

“…63 VEGF was also immobilized through a simple dipping methodology after PDA was deposited on the surface of a poly(l-lactide-co-e-caprolactone) (PLCL) film. 84 VEGFdopamine coatings demonstrated accelerated HUVEC migration and proliferation compared to dopamine-coated or uncoated PLCL films. The group also was able to immobilize basic fibroblast growth factor, demonstrating the versatility of the PDA immobilization techniques.…”