Department of Chemical Engineering, McMaster University, 1280 Main St. W., Hamilton, ON, Canada L8S 4L7.
J Biomater Sci Polym Ed. 2010;21(6-7):821-42. doi: 10.1163/156856209X445311.
While silicone elastomers generally have excellent biomaterials properties, their hydrophobicity can elicit undesired local biological responses through adsorption and denaturation of proteins. Surface-bound poly(ethylene glycol) (PEG) can ameliorate the situation by preventing contact between the external biology and the silicone elastomer. It is further possible to manipulate the biocompatibility of the surface by linking peptides, proteins or other biological entities to the PEG. Previous synthetic approaches to PEG-protected surfaces are compromised by issues of reproducibility. We describe two rapid and efficient approaches to silicone surface modification by PEG-linked adhesion peptides that overcome this problem: SiH groups are introduced throughout a silicone elastomer during elastomer synthesis or only at the surface after cure; then, in either case, protein-repellent PEG brushes at the surface are introduced by hydrosilylation to give surfaces that can be stored for extensive periods of time without degradation. Activation of the free alcohol with an NSC group followed by immediate conjugation to relevant biological molecules occurs in high yields, as shown for RGDS and GYRGDS. High surface grafting density of the peptides was demonstrated using radiolabeling techniques. Biological activity was demonstrated by a 5-fold increase in cell adhesion on the peptide-modified surfaces when compared to unmodified PDMS control surfaces.
虽然硅橡胶弹性体通常具有优异的生物材料性能,但它们的疏水性会通过吸附和蛋白质变性引起不良的局部生物学反应。表面结合的聚乙二醇(PEG)可以通过防止外部生物与硅橡胶弹性体接触来改善这种情况。通过将肽、蛋白质或其他生物实体连接到 PEG 上,可以进一步控制表面的生物相容性。以前的 PEG 保护表面的合成方法受到重现性问题的影响。我们描述了两种通过 PEG 连接的粘附肽快速有效地修饰硅橡胶表面的方法:在弹性体合成过程中或在固化后仅在表面引入 SiH 基团;然后,在这两种情况下,通过硅氢化反应在表面引入蛋白质排斥性的 PEG 刷,从而得到可以储存很长时间而不会降解的表面。如 RGDS 和 GYRGDS 所示,用 NSC 基团激活游离醇,然后立即与相关生物分子进行缀合,产率很高。使用放射性标记技术证明了肽的高表面接枝密度。与未修饰的 PDMS 对照表面相比,细胞在肽修饰表面上的粘附增加了 5 倍,证明了生物活性。