有序微纳结构材料的制备及其对细胞的作用研究

发布时间：2018-12-21 07:12

【摘要】：细胞与微纳结构材料之间的相互作用是材料科学领域的研究重点之一。材料的物理化学性质对细胞的行为具有非常重要的调控作用,继而影响到细胞的黏附、增殖、迁移和分化等细胞行为和功能。通常材料表面的性质可以分为化学性质和物理性质。对材料表面进行化学基团修饰,可以改变细胞的黏附行为等,但细胞生长环境仍局限于二维平面。物理修饰不仅可以调节细胞黏附排列等行为,甚至可提供细胞培养的三维环境。目前改变材料表面物理形貌的方法有自组装技术、电子束刻蚀、纳米压印技术等。近些年来,由于自组装技术和光刻微加工技术可以在微纳米尺度范围内制备多尺寸多功能的微结构,因此越来越多应用于细胞培养领域。本论文结合自组装和光刻技术,构建二维及三维有序微纳结构材料,并用于细胞培养。研究内容如下:(1)利用自组装方法,制备出微纳多孔有序结构材料;进而再通过拉伸作用,获得孔穴变形的有序结构材料;通过细胞培养,发现孔穴形貌对细胞形貌和细胞排列产生诱导,探讨了不同拉伸倍数对细胞的取向排列诱导情况,拉伸倍数越高细胞定向排列越明显;在此基础上,通过对不同孔穴形貌的有序结构材料进行凝胶修饰的方法,实现了对细胞的黏附行为和定向排列行为的同时调控,这种材料有望为各向异性组织如心肌、血管等的研究提供一种新的方法。(2)提出了基于阶跃拉伸法制备有序结构材料的方法,通过对同一材料在不同区域的不同倍数拉伸,得到了一系列不同孔穴形貌相组合的有序结构材料;基于此方法,还获得了孔穴形貌渐变的有序结构材料;此外,细胞实验表明,肌腱细胞在渐变拉伸材料表面呈现无序至有序的渐变排列;这种细胞渐变排列为今后研究组织工程领域中的关节连接处等提供了研究基础。(3)基于水平接触曝光结合双向曝光的方法,获得了有序网格结构中空纤维;细胞实验表明,细胞可围绕管状结构黏附生长形成致密层;进而通过对中空纤维的药物凝胶灌注,获得了负载药物的功能性纤维,并探讨了功能性纤维对表面黏附细胞的影响;此外,还设计并制备得到了单进口多出口的纤维网络支架;这种具有贯穿通道且通透管壁的中空纤维及其纤维网络,有望在三维灌注细胞培养、药物缓释等领域中得到应用。
[Abstract]:The interaction between cells and nanomaterials is one of the most important issues in the field of material science. The physical and chemical properties of materials play an important role in regulating cell behavior, and then affect cell adhesion, proliferation, migration and differentiation. In general, the surface properties of materials can be divided into chemical and physical properties. Modification of the surface of the material with chemical groups can change the adhesion behavior of the cells, but the cell growth environment is still confined to the two-dimensional plane. Physical modification can not only regulate the behavior of cell adhesion, but also provide a three-dimensional environment for cell culture. At present, the methods to change the physical morphology of materials are self-assembly, electron beam etching, nano-imprint and so on. In recent years, self-assembly and photolithography techniques have been widely used in the field of cell culture because they can be used to fabricate multi-size and multi-functional microstructures in the range of microscale and nano-scale. In this paper, two-dimensional and three-dimensional ordered micro-nano structure materials were constructed by self-assembly and photolithography, and used in cell culture. The main contents of the study are as follows: (1) the micro-nano porous ordered structure materials were prepared by the self-assembly method, and then the ordered structure materials with pore deformation were obtained by drawing. Through cell culture, it was found that the pore morphology induced the cell morphology and cell alignment, and the different stretching times induced the cell orientation. The higher the stretching ratio, the more obvious the cell orientation was. On this basis, the adhesion and orientation behavior of the cells were regulated simultaneously by the gel modification of the ordered structure materials with different pore morphology. This material is expected to be anisotropic tissue such as myocardium. The study of blood vessels provides a new method. (2) the method of preparing ordered structure materials based on step stretching method is proposed, by drawing different times of the same material in different regions. A series of ordered structure materials with different pore morphology were obtained. On the basis of this method, the ordered structure materials with gradual pore morphology were obtained, and the cellular experiments showed that the tendon cells were disordered to orderly arranged on the surface of the gradients. This gradual arrangement of cells provides a basis for future research on joint junctions in the field of tissue engineering. (3) based on the method of horizontal contact exposure combined with bidirectional exposure, the ordered meshed hollow fibers are obtained. Cell experiments showed that the cells could form dense layers around the tubular structure, and then the drug loaded functional fibers were obtained through the drug gel perfusion of hollow fibers, and the effects of functional fibers on the surface adhesion cells were discussed. In addition, a fiber network scaffold with single inlet and multiple outlets was designed and prepared. The hollow fiber and its fiber network with penetrating channels and through the tube wall are expected to be applied in the fields of three-dimensional perfusion cell culture and drug delivery.
【学位授予单位】：东南大学
【学位级别】：博士
【学位授予年份】：2017
【分类号】：R318.08

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