Fucoidan and topography modification improved in situ endothelialization on acellular synthetic vascular grafts

Thrombogenesis remains the primary failure of synthetic vascular grafts.Endothelial coverage is crucial to provide an antithrombogenic surface.However,most synthetic materials do not support cell adhesion,and transanastomotic endothelial migration is limited.Here,a surface modification strategy using fucoidan and topography was developed to enable fast in situ endothelialization of polyvinyl alcohol,which is not endothelial cell-adhesive.Among three different immobilization approaches compared,conjugation of aminated-fucoidan promoted endothelial monolayer formation while minimizing thrombogenicity in both in vitro platelet rich plasma testing and ex vivo non-human primate shunt assay.Screening of six topographical patterns showed that 2μm gratings increased endothelial cell migration without inducing inflammation responses of endothelial cells.Mechanistic studies demonstrated that fucoidan could attract fibronectin,enabling integrin binding and focal adhesion formation and activating focal adhesion kinase(FAK)signaling,and 2μm gratings further enhanced FAK-mediated cell migration.In a clinically relevant rabbit carotid artery end-to-side anastomosis model,60%in situ endothelialization was observed throughout the entire lumen of 1.7 mm inner diameter modified grafts,compared to 0%of unmodified graft,and the four-week graft patency also increased.This work presents a promising strategy to stimulate in situ endothelialization on synthetic materials for improving long-term performance.

In vitro biocompatibility evaluation of silk-fibroin/ polyurethane membrane with cultivation of HUVECs

In order to investigate the in vitro biocompatibility of a novel polyurethane （PU） membrane modified by incorporation of superfine silk-fibroin powder （SFP）, which was prepared for small-diameter vascular grafts, with the cultivation of human umbilical vein endothelial cells （HUVECs）, PU and SFP were mixed with the ratios of 9：1, 7：3, 5：5, 3：7 （PU：SFP） to make four composite materials. Unmodified PU and polytetrafluoroethylene （PTFE） were added as control groups. CCK-8 assay was used to evaluate the cytotoxicity of these biomaterials. Data were processed using SPSS, and P〈 0.05 was considered to be statistically significant. Adherence and spreading of HUVECs on the surface of specimens was observed using direct contact cultivation. The toxicity ratings of the novel composites were grade 0-1, which is in the acceptable range. In all the experimental groups except control, SFP/PU with ratio of 1：9 had the least cytotoxicity property, and more content of SFP in the composite showed no improvement of the biocompatibility. HUVECs strongly attached to and grew on the surface of the biomaterials, and proliferated rapidly. The proliferation ability increased with increased proportion of SFP; however the cell quantity on the surface of the materials decreased when the proportion of SFP was equal to or larger than that of PU in the composite. It is concluded that this novel material has excellent cellular affinity with no cytotoxicity to HUVECs. Adding SFP gives PU better biocompatibility, while further research on optimum blend ratios is still needed.