SYNTHESIS, SURFACE, AND CELL-ADHESION PROPERTIES OF POLYURETHANES CONTAINING COVALENTLY GRAFTED RGD-PEPTIDES

SYNTHESIS, SURFACE, AND CELL-ADHESION PROPERTIES OF POLYURETHANES CONTAINING COVALENTLY GRAFTED RGD-PEPTIDES
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DOI:
10.1002/jbm.820280307
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发表时间:
1994-03-01
期刊:
JOURNAL OF BIOMEDICAL MATERIALS RESEARCH
影响因子:
--
通讯作者:
COOPER, SL
COOPER, SL
中科院分区:
其他
文献类型:
--
作者:
LIN, HB;SUN, W;COOPER, SL

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为了改善内皮细胞在聚氨酯共聚物上的粘附和生长,将细胞粘附性含RGD的肽接枝到聚合物主链上。开发了两种肽接枝反应方案,包括一步法和两步法。红外光谱和氨基酸分析证实,通过一步法和两步法实现了肽到聚氨酯主链的偶联。然而,两步法显示出更高的肽偶联效率,并导致更好地控制接枝肽的取向。两步反应方案用于制备具有两种不同肽密度(100和250 μ mol/g聚合物)的Gly-Arg-Gly-Asp-Ser-Tyr(GRGDSY)、GL-Arg-Gly-Asp-Val-Tyr(GRGDVY)和Gly-Arg-Gly-Glu-Ser-Tyr(GRGESY)肽接枝的聚氨酯。动态接触角测量表明,肽接枝聚氨酯的表面比起始和羧化版本的前体聚氨酯更亲水。此外,肽接枝的聚合物的表面亲水性随着本体肽密度的增加而增加。化学分析的电子光谱表明,接枝肽存在于聚合物-空气界面,在真空中,接枝肽的聚氨酯。表面肽密度似乎与体积中掺入的肽密度相关。体外内皮细胞粘附实验表明,在培养基中不存在血清的情况下,与起始、羧化和GRGESY接枝的聚合物相比,GRGDSY和GRGDVY接枝的聚氨酯显著增强了细胞附着和扩散。对于GRGDSY-和GRGDVY-接枝的聚氨酯,将肽密度从100 μ mol/g增加到250 μ mol/g聚合物导致细胞附着增加。在大约相同的肽密度(100或250 μ mol/g聚合物)下,GRGDVY接枝的聚合物比GRGDSY接枝的聚合物支持更多的贴壁细胞。在使用含血清和内皮细胞生长补充剂的培养基进行的体外内皮细胞生长研究中观察到类似趋势。GRGDSY和GRGDVY接枝的聚氨酯比起始聚氨酯促进更多的细胞生长。然而,粘附血清蛋白和生长因子的存在减少了细胞粘附肽接枝聚合物和GRGESY接枝聚合物之间的差异。(C)1994年,John Wiley and Sons,Inc.
In an attempt to improve endothelial cell adhesion and growth on a polyurethane copolymer, cell adhesive RGD-containing peptides were grafted to the polymer backbone. Two peptide grafting reaction schemes, including one-step and two-step approaches, were developed. FTIR and amino acid analysis confirmed that coupling of the peptide to the polyurethane backbone was achieved by both the one-step and two-step methods. However, the two-step approach showed a higher peptide coupling efficiency and resulted in better control of the orientation of the grafted peptide. The two-step reaction scheme was used to prepare Gly-Arg-Gly-Asp-Ser-Tyr (GRGDSY), GL-Arg-Gly-Asp-Val-Tyr (GRGDVY), and Gly-Arg-Gly-Glu-Ser-Tyr (GRGESY) peptide-grafted polyurethanes with two different peptide densities (100 and 250 mu mol/g polymer). Dynamic contact angle measurements indicated that the surfaces of the peptide-grafted polyurethanes were more hydrophilic than the starting and carboxylated versions of the precursor polyurethane. In addition, the surface hydrophilicity of the peptide-grafted polymers increased with increasing bulk peptide density. Electron spectroscopy for chemical analysis suggested that the grafted peptide was present at the polymer-air interface, in vacuo, fdr the peptide-grafted polyurethanes. The surface peptide density appeared to correlate with the incorporated peptide density in the bulk In vitro endothelial cell adhesion experiments showed that, without the presence of serum in culture medium, the GRGDSY- and GRGDVY-grafted polyurethanes dramatically enhanced cell attachment and spreading compared with the starting, carboxylated, and GRGESY-grafted polymers. Increasing the peptide density from 100 to 250 mu mol/g polymer for the GRGDSY- and GRGDVY-grafted polyurethanes resulted in an increase in cell attachment. With approximately the same peptide density (100 or 250 mu mol/g polymer), the GRGDVY-grafted polymers supported more adherent cells than did the GRGDSY-grafted polymers. Similar trends were observed in the in vitro endothelial cell growth studies using culture medium containing serum and endothelial cell growth supplement. The GRGDSY- and GRGDVY-grafted polyurethanes promoted more cell growth than did the starting polyurethane. However, the presence of adhesive serum proteins and growth factor diminished the differences between the cell-adhesive peptide grafted polymers and the GRGESY-grafted polymers. (C) 1994 John Wiley and Sons, Inc.