Abstract

Small-diameter (<6 mm) vascular grafts are increasingly needed in peripheral vascular surgery but have few successes because of acute thrombosis, incomplete endothelialization and intimal hyperplasia after implantation. This study used electrospun poly(ε-caprolactone) as the matrix material. Heparin and selenium-containing catalyst-organoselenium modified polyethyleneimine were introduced through layer-by-layer assembly in order to build a vascular graft with in situ nitric oxide (NO) generation. The aim of this study was to explore the application of the graft with improved histocompatibility and biological function for vascular implantation in rats. After implantation in rats, compared to poly(ε-caprolactone), the modified grafts could promote the adhesion and proliferation of endothelial cells, and inhibit the adhesion of smooth muscle cells. The modified grafts remarkably promoted endothelialization, inhibited intimal hyperplasia and increased the ratio of alternatively activated macrophages (M2) to classical activated macrophages (M1). This work constructed a vascular graft with heparinization and catalytic NO generation for improving the vascularization, and accelerating the tissue regeneration by regulating the inflammatory response. The present study indicates that it is a promising method for regulating response and tissue regeneration of small diameter vascular grafts by a novel approach of combining heparinization and catalytic NO generation.

Highlights

  • Vascular diseases, cardiovascular disease, are the number one cause of death globally [1, 2]

  • The outlines of the electrospun fibrous films had no significant change after surface modification

  • The formation of endothelium on PCL-(SePEI/Hep)10 sample was clearly better than that on PCL (Fig. 4), while the thickness of the smooth muscle layer on PCL-(SePEI/Hep)10 sample was smaller than that on PCL (Fig. 6). It meant that the introduction of heparin improved the attachment of endothelial cells (ECs) and inhibited the proliferation of smooth muscle cell (SMC), and nitric oxide (NO) could improve this effect on the basis of heparin

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Summary

Introduction

Cardiovascular disease, are the number one cause of death globally [1, 2]. Synthetic grafts perform poorly in small-diameter vascular grafts because of acute thrombosis and intimal hyperplasia (IH) after implantation [5, 6]. There is a substantial need for small-diameter vascular grafts as bypass and blood vessel replacement. The ideal vascular graft should have the ability to promote endothelialization, inhibit IH and enhance the regeneration of tissue. Endothelialization is important for artificial vascular grafts, because it can provide an appropriate compatible surface to guarantee blood flow and control smooth muscle cell (SMC) proliferation [7]. Selective promotion of endothelial cells (ECs) in competitive adhesion against SMCs can get a balanced behavior of ECs and SMCs for reduced thrombosis and IH [8, 9]

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