Green Tea Polyphenol Sandwich-Assisted Construction of Endothelial Biomimetic Coatings with Hyaluronic Acid Platform and Nitric Oxide Release for Hemodialysis Access Stents to Prevent Thrombosis and Restenosis

Background: Vascular stent is one of the main means of treating dialysis access stenosis. However, in-stent thrombosis (IST) and in-stent restenosis (ISR) always limit effectiveness of stents in clinical applications. Vascular endothelial cells play an important role in regulating the physiological structure and function of vessels, so endowing vascular stents with the bionic function of endothelial cells is an effective solution to address complications such as IST and ISR. Methods: In this paper, an endothelial bionic coating for stents constructed by layer-by-layer self-assembly method was developed. We used positively charged polyethyleneimine (PEI) and negatively charged hyaluronic acid (HA) as polyelectrolytes, assisted construction by a chelate sandwich of epigallocatechin gallate (EGCG) with copper (Cu). The biocompatibility of the coatings was verified by systematic materialogical characterization, in vitro and ex in vivo hemocompatibility experiments, in vitro cell culture experiments, and in vivo experiments of subcutaneous implantation and stent implantation. Results: The results showed that this strategy was able to improve the loading, stability and homogeneity of the coating through various interations, such as electrostatic adsorption, hydrogen bonding, π-π stacking, and chemical cross-linking of phenalkamines. The coating was able to synergistically improve the antithrombotic ability of vascular scaffolds with HA and nitric oxide, and promote the rapidly endothelialization of the stents, inhibit intimal hyperplasia and regulate the inflammatory response. Conclusion: This polyelectrolyte endothelial biomimetic coating constructed by metal polyphenol sandwich can effectively reduce complication such as IST and ISR of stents and improve the clinical outcomes of vascular stenting for dialysis access stenosis.The scheme of coating for hemodialysis access stents to prevent IST and ISR.