Scott Evan A, Nichols Michael D, Cordova Lee H, George Brandon J, Jun Young-Shin, Elbert Donald L
Department of Biomedical Engineering and Center for Materials Innovation, Washington University in St. Louis, Campus Box 1097, One Brookings Drive, St. Louis, MO 63105, USA.
Biomaterials. 2008 Dec;29(34):4481-93. doi: 10.1016/j.biomaterials.2008.08.003. Epub 2008 Sep 3.
Late-term thrombosis on drug-eluting stents is an emerging problem that might be addressed using extremely thin, biologically active hydrogel coatings. We report a dip-coating strategy to covalently link poly(ethylene glycol) (PEG) to substrates, producing coatings with approximately <100 nm thickness. Gelation of PEG-octavinylsulfone with amines in either bovine serum albumin (BSA) or PEG-octaamine was monitored by dynamic light scattering (DLS), revealing the presence of microgels before macrogelation. NMR also revealed extremely high end-group conversions prior to macrogelation, consistent with the formation of highly crosslinked microgels and deviation from Flory-Stockmayer theory. Before macrogelation, the reacting solutions were diluted and incubated with nucleophile-functionalized surfaces. Using optical waveguide lightmode spectroscopy (OWLS) and quartz crystal microbalance with dissipation (QCM-D), we identified a highly hydrated, protein-resistant layer with a thickness of approximately 75 nm. Atomic force microscopy in buffered water revealed the presence of coalesced spheres of various sizes but with diameters less than about 100 nm. Microgel-coated glass or poly(ethylene terephthalate) exhibited reduced protein adsorption and cell adhesion. Cellular interactions with the surface could be controlled by using different proteins to cap unreacted vinylsulfone groups within the coating.
药物洗脱支架晚期血栓形成是一个新出现的问题,或许可以通过使用极薄的生物活性水凝胶涂层来解决。我们报道了一种浸涂策略,可将聚乙二醇(PEG)共价连接到基底上,制备出厚度约<100 nm的涂层。通过动态光散射(DLS)监测PEG - 八乙烯基砜与牛血清白蛋白(BSA)或PEG - 八胺中的胺的凝胶化过程,发现在宏观凝胶化之前存在微凝胶。核磁共振(NMR)还显示在宏观凝胶化之前端基转化率极高,这与高度交联的微凝胶的形成以及偏离弗洛里 - 斯托克迈耶理论一致。在宏观凝胶化之前,将反应溶液稀释并与亲核试剂功能化的表面孵育。使用光波导光模光谱(OWLS)和带耗散的石英晶体微天平(QCM - D),我们鉴定出了一层高度水合、抗蛋白质的层,其厚度约为75 nm。在缓冲水中进行的原子力显微镜观察显示存在各种尺寸但直径小于约100 nm的聚结球体。微凝胶涂层的玻璃或聚对苯二甲酸乙二酯表现出减少的蛋白质吸附和细胞粘附。通过使用不同的蛋白质来封端涂层中未反应的乙烯基砜基团,可以控制细胞与表面的相互作用。