Patel Shyam, Thakar Rahul G, Wong Josh, McLeod Stephen D, Li Song
Department of Bioengineering, University of California-Berkeley, 471 Evans Hall #1762, 94720, USA.
Biomaterials. 2006 May;27(14):2890-7. doi: 10.1016/j.biomaterials.2005.12.009. Epub 2006 Jan 24.
Keratoprostheses have been constructed from a wide variety of transparent materials, including poly(methyl methacrylate) (PMMA). However, the success of keratoprosthesis has been plagued by numerous shortcomings that include the weakening of the implant-host interface due to weak cell adhesion and opaque fibrous membrane formation over the inner surface of the implant due to fibroblast attachment. An effective solution requires a surface modification that would selectively allow enhanced cell attachment at the implant-host interface and reduced cell attachment over the interior surface of the implant. Here, we have developed a novel and simple peptide conjugation scheme to modify PMMA surfaces, which allowed for region-specific control of cell adhesion. This method uses di-amino-PEG, which can be grafted onto PMMA using hydrolysis or aminolysis method. PEG can resist cell adhesion and protein adsorption. The functionalization of grafted di-amino-PEG molecules with RGD peptide not only restored cell adhesion to the surfaces, but also enhanced cell attachment and spreading as compared to untreated PMMA surfaces. Long-term cell migration and micropatterning studies clearly indicated that PEG-PMMA surfaces with and without RGD conjugation can be used to differentiate cell adhesion and control cell attachment spatially on PMMA, which will have potential applications in the modification of keratoprostheses.
角膜假体已由多种透明材料制成,包括聚甲基丙烯酸甲酯(PMMA)。然而,角膜假体的成功一直受到众多缺点的困扰,这些缺点包括由于细胞粘附力弱导致植入物与宿主界面减弱,以及由于成纤维细胞附着在植入物内表面形成不透明纤维膜。一个有效的解决方案需要进行表面修饰,以选择性地增强植入物与宿主界面处的细胞附着,并减少植入物内表面的细胞附着。在此,我们开发了一种新颖且简单的肽偶联方案来修饰PMMA表面,从而实现对细胞粘附的区域特异性控制。该方法使用二氨基聚乙二醇(di-amino-PEG),它可以通过水解或氨解方法接枝到PMMA上。聚乙二醇可以抵抗细胞粘附和蛋白质吸附。用RGD肽对接枝的二氨基聚乙二醇分子进行功能化不仅恢复了细胞对表面的粘附,而且与未处理的PMMA表面相比,增强了细胞附着和铺展。长期的细胞迁移和微图案化研究清楚地表明,带有和不带有RGD偶联的聚乙二醇-PMMA表面可用于区分细胞粘附并在空间上控制PMMA上的细胞附着,这将在角膜假体的修饰中具有潜在应用。