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Controlled polymerization chemistry to graft architectures that influence cell-material interactions.

机译:控制聚合化学反应到影响细胞-材料相互作用的接枝结构。

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Acrylate monomers were photografted from polymer substrates to create cell responsive chemically and biologically active surfaces that manipulate cell response. Three monomers, polyethylene glycol monoacrylate (MW 375 g/mol) (PEG375A), a monomeric extra-cellular matrix protein, and a cell-cleavable fluorescent monomer, were spatially photopatterned from a base substrate. The base substrate consisted of a dithiocarbamate (DTC) functionalized urethane diacrylate/tri(ethylene glycol)diacrylate copolymer and was shown to non-specifically support NIH 3T3 fibroblast cell adhesion. The DTC-containing polymer was further modified by grafting PEG375A to demonstrate selective blocking of cell-material interactions. Next, acrylated collagen type I was patterned onto polymer substrates to further promote specific cell interactions (i.e. by presenting cell-adhesive moieties). Hydrophilic PEG375A grafted patterns were shown to prevent 3T3 fibroblast adhesion to polymer in spatially grafted regions, while biologically active acrylated collagen type I promoted cell-surface interactions. Collagen type I was grafted at varying densities (0-7.5 pmol/grafted square), and the extent of cell adhesion and spreading were evaluated for each of these graft densities using fluorescence microscopy. Finally, methacrylated carboxyfluorescein diacetate (CFDA) was synthesized and photografted onto a cell-adhesive substrate as a cell sensing mechanism. The acetate groups found in the structure of CFDA cleave in the presence of cells. This cell-responsive substrate results in fluorescence indicative of acetate-group cleavage associated with cell interactions that occurs in patterned regions on polymer surfaces. Collectively, the results herein show the utility and application of a spatially and temporally controlled photografting process for designing cell responsive polymer surfaces.
机译:从聚合物基材上光接枝丙烯酸酯单体,以产生可控制细胞反应的细胞反应性化学和生物活性表面。从基础基材上对三种单体进行空间光图案化:聚乙二醇单丙烯酸酯(MW 375 g / mol)(PEG375A),单体细胞外基质蛋白和可细胞裂解的荧光单体。基础基材由二硫代氨基甲酸酯(DTC)官能化的氨基甲酸酯二丙烯酸酯/三(乙二醇)二丙烯酸酯共聚物组成,并显示出非特异性地支持NIH 3T3成纤维细胞粘附。通过接枝PEG375A进一步修饰含DTC的聚合物,以证明选择性阻断细胞与材料的相互作用。接下来,将I型丙烯酸化的胶原蛋白图案化到聚合物基底上,以进一步促进特定的细胞相互作用(即,通过提供细胞-粘附部分)。亲水性PEG375A的接枝模式显示可防止3T3成纤维细胞粘附于空间接枝区域中的聚合物,而具有生物活性的丙烯酸酯化I型胶原促进细胞表面相互作用。将I型胶原蛋白以不同的密度(0-7.5 pmol /嫁接的正方形)进行移植,并使用荧光显微镜对每种移植密度评估细胞粘附和扩散的程度。最后,合成了甲基丙烯酸化的羧基荧光素二乙酸酯(CFDA),并将其光接枝到细胞粘附性基质上,作为细胞传感机制。在细胞存在下,CFDA结构中发现的乙酸酯基会裂解。该细胞响应性底物产生荧光,该荧光指示与在聚合物表面上的图案化区域中发生的细胞相互作用有关的乙酸酯基裂解。总体而言,本文的结果显示了用于设计细胞响应性聚合物表面的空间和时间控制的光接枝方法的实用性和应用。

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