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通过将血管内皮生长因子固定在细胞排斥型功能性聚氨基甲酸酯上来实现内皮细胞化。

Toward endothelialization via vascular endothelial growth factor immobilization on cell-repelling functional polyurethanes.

机构信息

Department of Polymeric Biomaterials and Artificial Organs, College of Polymer Science and Engineering, Sichuan University, Chengdu, Sichuan 610065, China.

Department of Gastrointestinal Surgery, West China Hospital and State Key Laboratory of Biotherapy, Sichuan University, Chengdu, Sichuan 610041, China.

出版信息

J Biomed Mater Res B Appl Biomater. 2019 May;107(4):965-977. doi: 10.1002/jbm.b.34190. Epub 2018 Sep 28.

DOI:10.1002/jbm.b.34190
PMID:30265778
Abstract

We screened a family of nonspecific cell-repelling polyurethanes (PUs) whose backbones are attached with epoxy group-terminated polyethylene glycol (PEG) side chains. Water incubation of the PU films (with 9.2-31.1 wt % PEG) caused a surface enrichment of PEG chains where vascular endothelial growth factor (VEGF) was grafted by forming secondary amine linkages between VEGF molecules and the PEG spacer. These linkages are still ionizable similar to original primary amines in VEGF, thereby retaining the original charge distribution on VEGF macromolecules. This charge conservation together with PEG steric repulsion helped to preserve VEGF conformation and bioactivity. The PU substrates with suitable hard segments contents and VEGF surface densities can selectively induce endothelial cells (ECs) adhesion and proliferation toward endothelialization. Moreover, the PU substrates, even grafted with fibrinogen (Fg), cannot trigger platelet adhesion and deformation, suggesting an inactive conformation of the grafted Fg. Thus enough antithrombogenicity of the PU substrates could be expected before full endothelialization. These PU materials might be applied onto the lumens of vascular grafts, potentially stimulating luminal endothelialization in vivo. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 965-977, 2019.

摘要

我们筛选了一系列非特异性细胞排斥型聚氨酯(PU),其骨架连接有环氧封端的聚乙二醇(PEG)侧链。将 PU 薄膜(PEG 含量为 9.2-31.1wt%)在水中孵育,会导致 PEG 链在表面富集,其中血管内皮生长因子(VEGF)通过 VEGF 分子和 PEG 间隔物之间形成二级胺键接枝。这些键仍然是可离子化的,类似于 VEGF 中原始的伯胺,从而保持 VEGF 大分子的原始电荷分布。这种电荷守恒与 PEG 空间排斥一起有助于保持 VEGF 构象和生物活性。具有合适硬段含量和 VEGF 表面密度的 PU 基底可以选择性地诱导内皮细胞(ECs)向内皮化方向黏附和增殖。此外,即使接枝纤维蛋白原(Fg)的 PU 基底也不能引发血小板黏附和变形,表明接枝 Fg 处于无活性构象。因此,在完全内皮化之前,可以预期 PU 基底具有足够的抗血栓形成性。这些 PU 材料可能应用于血管移植物的内腔,有可能在体内刺激内腔内皮化。© 2018 年 Wiley 期刊,生物医学材料研究部分 B:应用生物材料 107B:965-977,2019。

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