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Application of nanobiomaterials for biofouling attenuation.

机译:纳米生物材料在生物污损衰减中的应用。

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The research described here investigates the hypothesis that surface nanoarchitecture is capable of attenuating the adverse host response generated when medical devices are implanted in the body. This adverse host response, or biofouling, generates an avascular fibrous mass transfer barrier between the device and extracellular environment, disabling the implant if it is a sensor. Numerous studies have indicated that surface chemistry and architecture modulate the host response. These findings led me to hypothesize that nanostructured surfaces will significantly inhibit the formation of an avascular fibrous capsule. We are investigating whether arrays of oscillating magnetostrictive nanowires, a nanostructured PTFE (nPTFE) surface, or a hyperbranched poly(ethylene glycol) (PEG) and poly(allylamine) (PAAM) surface can prevent protein adsorption and cell adhesion. Magnetostrictive nanowires were fabricated by electroplating a ferromagnetic metal alloy into the pores of a nanoporous alumina template. Nanostructured PTFE coatings were created by jet-blowing PTFE onto glass surfaces. Hyperbranched surfaces were created by alternating layers of PAAM and PEG on silicon. Protein adsorption results displayed a reduced amount of protein per surface area of static nanowires, significant at an initial concentration of 1 mg/mL bovine serum albumin (BSA). This attenuation of protein adsorption was increased by vibrating the nanowires. Reduced protein adsorption was linked to the increased hydrophilicity of the static wires and shear-linked detachment of proteins on vibrating nanowires. Albumin adsorption on the nPTFE surface was slightly higher than that found in literature. The hyperbranched polymer surface showed an attenuation of protein adsorption with both the PEG and PRAM surfaces. The PEG has a much higher rejection rate of protein compared to the PRAM surface; however both surfaces adsorbed less protein than silicon. An additional study addressed cell adhesion, in particular, macrophage, fibroblast and endothelial cell adhesion. We found that the cells on the nanowires and nPTFE typically occupy less area and are more circular than on a flat surface of the same material (control wafers) or tissue culture polystyrene (TCPS), respectively. Furthermore, this difference is amplified by pre-coating the nanostructured surfaces with collagen. This circular, non-spread shape has been linked to non-thriving cells and indeed the dead cell to live cell ratio of fibroblasts on the surfaces was significantly higher compared to the ratio tissue on the respective control. Since there is a high amount of cell death, and the process of biofouling is a chronic inflammation, an eighteen cytokine LuminexRTM panel was performed on the supernatant from the surface. The results conclude that the nanowires are immunogenic whereas the nPTFE surface was not. Overall, the thesis shows that nanoarchitecture can disrupt adsorption of protein. And by disrupting the protein adsorption on the surface, cell adhesion is significantly altered also. These results indicate that a nanostructured surface could significantly reduce the biofouling response in vivo. Further studies would need to be characterized to conclude the viability of such an implant surface.
机译:此处描述的研究调查了以下假说:表面纳米结构能够减弱将医疗设备植入体内时产生的不良宿主反应。这种不利的宿主反应或生物污染,会在设备与细胞外环境之间产生无血管的纤维质传递屏障,如果植入物是传感器,则会使植入物失效。大量研究表明,表面化学和结构可调节宿主反应。这些发现使我假设纳米结构的表面将显着抑制无血管纤维囊的形成。我们正在研究振荡的磁致伸缩纳米线,纳米结构的PTFE(nPTFE)表面或超支化的聚乙二醇(PEG)和聚(烯丙胺)(PAAM)表面是否可以防止蛋白质吸附和细胞粘附。磁致伸缩纳米线是通过将铁磁金属合金电镀到纳米多孔氧化铝模板的孔中而制成的。纳米结构的PTFE涂层是通过将PTFE喷吹到玻璃表面上而形成的。超支化表面是通过在硅上交替排列PAAM和PEG层而形成的。蛋白质吸附结果显示,每单位静态纳米线表面积的蛋白质减少量,在初始浓度为1 mg / mL牛血清白蛋白(BSA)时显着。振动纳米线增加了蛋白质吸附的衰减。蛋白质吸附的减少与静电线的亲水性增加以及振动纳米线上蛋白质的剪切连锁分离有关。 nPTFE表面的白蛋白吸附量比文献中的吸附量略高。超支化聚合物表面在PEG和PRAM表面均显示出蛋白质吸附的减弱。与PRAM表面相比,PEG具有更高的蛋白质排斥率。但是,两个表面吸附的蛋白质都少于硅。另一项研究针对细胞粘附,特别是巨噬细胞,成纤维细胞和内皮细胞粘附。我们发现,与相同材料(控制晶片)或组织培养聚苯乙烯(TCPS)的平坦表面相比,纳米线上和nPTFE上的细胞通常占据的面积较小,并且圆形程度更高。此外,通过用胶原蛋白预涂覆纳米结构表面来扩大这种差异。这种圆形的,未铺展的形状与非活跃细胞有关,实际上,与相应对照组的组织比率相比,表面上成纤维细胞的死细胞与活细胞比率明显更高。由于存在大量细胞死亡,并且生物污染的过程是慢性炎症,因此对表面上清液进行了18种细胞因子LuminexRTM的检测。结果得出结论,纳米线具有免疫原性,而nPTFE表面则没有。总的来说,论文表明纳米结构可以破坏蛋白质的吸附。并且通过破坏蛋白质在表面上的吸附,细胞粘附也会显着改变。这些结果表明,纳米结构的表面可以显着降低体内的生物污染反应。需要进一步研究以总结出这种植入物表面的可行性。

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