Development of a YIGSR-peptide-modified polyurethaneurea to enhance endothelialization
Development of a YIGSR-peptide-modified polyurethaneurea to enhance endothelialization
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DOI：
10.1163/156856204322752246
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发表时间：
2004-01-01
影响因子：
3.6
通讯作者：
West, J
中科院分区：
文献类型：
--
作者：
Jun, HW;West, J
由于其优异的机械性能和相对良好的生物相容性，已研究了用作血管移植物的聚乙烯。然而，内皮细胞的不良保留和体内血栓形成对于血管移植物应用仍然是个问题。肽YIGSR已显示增加内皮细胞粘附，但不增加血小板的附着，表明其可能用于血管移植应用。在这项研究中，生物活性的聚脲已被合成通过将GGGYIGSRGGGGK肽序列到聚合物骨架。通过NMR、接触角测量和ESCA证实了肽的成功掺入。使用能够与肽上的酪氨酸残基反应的荧光探针观察到肽在表面上的均匀分布。使用轻敲模式AFM可视化硬段域。与对照聚脲相比，生物活性聚脲改善了内皮细胞的粘附、铺展、增殖、迁移和细胞外基质的产生。可溶性YIGSR肽竞争性抑制内皮细胞粘附和扩散表明细胞粘附和扩散是由YIGSR敏感的细胞粘附受体特异性介导的，而不仅仅是通过改变表面性质。粘附血小板数无显著差异。因此，这种生物活性聚脲可以改善血管移植物内皮化而不增加血栓形成。
Polyurethanes have been investigated for use as vascular grafts due to their excellent mechanical properties and relatively good biocompatibility. However, poor retention of endothelial cells and thrombogenicity in vivo remain problematic for vascular graft applications. The peptide YIGSR has been shown to increase endothelial cell adhesion but not attachment of platelets, suggesting its possible utility for vascular graft applications. In this study, a bioactive polyurethaneurea has been synthesized by incorporating GGGYIGSRGGGK peptide sequences into the polymer backbone. Successful incorporation of the peptides was confirmed by NMR, contact angle measurement and ESCA. Uniform distribution of peptides on the surface was observed using a fluorescent probe capable of reacting with tyrosine residues on the peptides. Hard segment domains were visualized using tapping mode AFM. Endothelial cell adhesion, spreading, proliferation, migration and extra-cellular matrix production were improved on bioactive polyurethaneurea compared to control polyurethaneurea. Competitive inhibition of endothelial cell attachment and spreading by soluble YIGSR peptides indicated that cell adhesion and spreading were specifically mediated by YIGSR-sensitive cell adhesion receptor, not just by changed surface properties. There was no significant difference in the number of adherent platelets. Therefore, this bioactive polyurethanurea may improve vascular graft endothelialization without increasing thrombogenicity.