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类型 基础研究 预答辩日期 2018-04-04
开始(开题)日期 2016-06-15 论文结束日期 2018-01-16
地点 逸夫科技馆三楼会议室 论文选题来源 国家自然科学基金项目     论文字数 6.7 (万字)
题目 基于生物相容性光子晶体的细胞培养和药物评估应用
主题词 生物相容性,光子晶体,结构色,器官芯片,药物筛选
摘要 结构色材料是一种具有有序微纳结构的材料,它可以与光相互作用而产生颜色。其独特的周期性微纳结构和光学传感特性,使其在组织工程、细胞行为学研究、药物筛选和生物发育等方面有着巨大的潜在应用价值。在细胞研究中,细胞与材料间的相互作用一直是研究的热点。主要包括细胞在材料表面的吸附、生长、增殖、分化和凋亡等多种行为。因此,基于结构色材料构建的检测平台,在细胞与材料相互作用的研究中,将发挥重要作用。和其他检测平台相比,基于结构色材料构建的细胞检测平台,不需要荧光染色,避免了待检细胞死亡或荧光猝灭等现象的发生。其本身具有高效、稳定且不受外界干扰的光学编码元素,可在不伤害细胞的情况下,实现细胞生理过程的实时监测,比如细胞的增殖、分化、凋亡和趋性等过程。本论文主要阐述了生物相容性反蛋白石结构色水凝胶材料在细胞传感中的研究,构建了基于结构色材料的器官芯片,开发其在药物筛选和评估等领域中的应用,具体内容如下: (1)以二氧化硅胶体粒子为构筑基元,制备了光子晶体膜、光子晶体纤维、光子晶体微球模板。基于生物相容性GelMA水凝胶和光子晶体模板,获得了生物相容性的反蛋白石GelMA水凝胶膜、GelMA水凝胶纤维和核-壳GelMA水凝胶球形光子晶体微载体。 (2)基于反蛋白石GelMA水凝胶支架,向反蛋白石孔洞中填充具有自修复功能的BSA水凝胶体系,实现了自修复结构色水凝胶的制备。利用自修复结构色水凝胶,实现了一、二、三维结构色图案的修复、防伪标签的制备,并将其应用到细胞传感等研究领域。 (3)基于反蛋白石GelMA水凝胶膜,进行了心肌细胞的培养。借助心肌细胞的周期性收缩,实现了结构色水凝胶材料的主动调控。利用条纹反蛋白石GelMA水凝胶膜的表面拓扑形貌,使得心肌细胞能够取向生长,为在体外模拟心脏功能提供了高活性的心肌细胞。 (4)基于条纹反蛋白石GelMA水凝胶膜,构建了用于心肌细胞传感的心脏芯片。借助条纹反蛋白石GelMA水凝胶的光学传感特性,实现了心肌细胞收缩力和跳动频率的监测,并将其用于心脏药物(异丙肾上腺素)的评估。 (5)基于核-壳GelMA水凝胶球形光子晶体微载体,培养得到高活力、高表型和功能的肝细胞(HepG2)、肿瘤细胞(HCT-116)和成纤维细胞(NIH-3T3)聚集体。 (6)基于核-壳 GelMA水凝胶球形光子晶体微载体培养的HepG2,HCT-116 NIH-3T3细胞聚集体,构建了混合培养体系,并用于抗肿瘤药物替加氟的代谢途径研究。在该体系中,HepG2细胞聚集体将替加氟代谢为抗肿瘤药物5-氟尿嘧啶,并对HCT-116细胞表现出细胞毒性。
英文题目 Fabrication of biocompatible photonic crystal and their applications in cell culture and drug screening
英文主题词 Biocompatibility,Photonic crystal,Structural colors,Organ on chips,Drug screening
英文摘要 Structural colors, originating from the physical interaction of light with intrinsic periodic nanostructures, have attracted much interest. It has been widely studied and used in tissue engineering, cell behavior, drug screening and other biological processes. In cytological studies, the interaction between cells and materials has been a hot topic, such as adsorption, growth, proliferation and differentiation. Therefore, the development of a detection platform based on structure color materials, will play an important role in the study of the interactions between cell and material. Unlike some others, the cellular detection platforms based on structural color materials do not require fluorescent staining, therefore avoiding the occurrence of cell death or fluorescence quenching. The encoding strategy of structure color materials was highly efficient, stable, and undisturbed. It can realize real-time detection of cellular physiological processes without cells damage. Herein, we focused on this goal and developed organ-on-chips based on the structural color hydrogels, and explored their applications in drug screening, evaluation and others biological analysis. The detail works are as follow: (1) The photonic crystal templates, such as photonic crystal films, photonic crystal fibers and photonic crystal beads were fabricated by self-assembly of silica nanoparticles. The inverse structural color materials were fabricated by replicating photonic crystal templates. (2) The self-healing structural color hydrogels were prepared by constructing them with a composite nanostructure. This nanostructure was composed of a methacrylated gelatin (GelMA) hydrogel inverse opal scaffold and a filler of glutaraldehyde cross-linked BSA hydrogel. A series of unprecedented structural color materials, such as 1D linear structures, 2D patterns, and 3D counterfeit-prevention objects and photonic path structures, could be created by assembling and healing the elements of the composite hydrogel. We have demonstrated their different applications, such as counterfeit prevention, integrated optics, and biomedical engineering. (3) We have developed novel structural-color hydrogels that have autonomic regulation capability by assembling engineered cardiomyocyte tissues on soft inverse-opal GelMA hydrogel films. Taking advantage of the surface microgroove structure of structural colors films, the assembled cardiomyocytes with guided cellular orientation were achieved. These features make our self-healing structural color hydrogels highly promising for in vitro culture of high-activity cardiomyocytes. (4) Based on these biohybrid structural-color hydrogels, an unprecedented heart-on-a-chip device has been developed for biological research and drug (isoproterenol) screening. In this heart-on-a-chip platform, the cardiomyocytes contractile force and beating frequency were monitored. (5) A novel GelMA hydrogel-encapsulated core-shell PhC barcode particles were developed. It was used for high-activity organ cells (HepG2, HCT-116 and NIH-3T3) cultured. (6) On the basis of these core-shell PhC barcode particles, HepG2, HCT-116, and NIH-3T3 were cocultured into liver and tumor cell spheroids to test the cytotoxic effect of TF. The system appeared to reproduce the hepatic function of synthesizing P450 enzymes, which could convert the noncytotoxic TF to cytotoxic 5-FU and reveal its cytotoxicity.
学术讨论
主办单位时间地点报告人报告主题
东南大学 2015-06-08 逸夫科技馆 付繁繁 生物相容性反蛋白石水凝胶的制备
东南大学 2016-03-26 逸夫科技馆 付繁繁 核-壳光子晶体微球的制备
东南大学 2016-07-23 逸夫科技馆 付繁繁 基于核-壳光子晶体微载体的药物评估应用
东南大学 2016-10-26 逸夫科技馆 付繁繁 自修复结构色水凝胶的制备
东南大学 2016-12-18 逸夫科技馆 付繁繁 自修复结构色水凝胶在细胞培养方面的应用
东南大学 2017-03-25 逸夫科技馆 付繁繁 基于反蛋白石水凝胶心肌细胞的培养
东南大学 2017-08-26 逸夫科技馆 付繁繁 基于反蛋白石水凝胶心脏芯片的构建
东南大学 2017-12-30 逸夫科技馆 付繁繁 智能响应性光子晶体水凝胶的制备
     
学术会议
会议名称时间地点本人报告本人报告题目
SIEMME 2016 2016-09 苏州 Cells Cultured on Core-Shell Photonic Crystal Barcodes for Drug Screening
ICBNI 2017 2017-09 布里斯班 昆士兰大学 Bio-inspired self-healing structural color hydrogel
     
代表作
论文名称
Cells Cultured on Core?Shell Photonic Crystal Barcodes for Drug Screening
Bio-inspired self-healing structural color hydrogel
 
答辩委员会组成信息
姓名职称导师类别工作单位是否主席备注
陶纬国 正高 教授 博导 东南大学
刘颖 正高 教授 博导 南京大学
刘宏 正高 教授 博导 东南大学
曹毅 正高 教授 博导 南京大学
吴富根 正高 教授 博导 东南大学
      
答辩秘书信息
姓名职称工作单位备注
顾洪成 其他 讲师 东南大学