巯基壳聚糖—丙烯酰聚乙二醇水凝胶制备及内皮细胞相容性研究

发布时间：2018-03-21 02:30

本文选题：壳聚糖　切入点：聚乙二醇　出处：《西南交通大学》2017年硕士论文　论文类型：学位论文

【摘要】：冠心病作为最常见的心血管疾病之一,已严重威胁到人类的健康。目前,临床上最有效的方法是介入治疗法,即在病变处植入血管支架,使原本已堵塞的血管畅通。但是,支架在植入及撑开时容易造成血管壁损伤、导致内膜层受损,从而引发再狭窄和血栓等并发症。近期国内外学者主要研究是,在支架表面进行生物功能化构建,使支架植入人体后可以快速形成一层内皮,加速损伤内皮层的修复和重建,从而解决术后并发症问题。本论文通过在金属钛箔表面沉积多巴胺涂层,并沉积巯基壳聚糖/聚乙二醇二丙烯酸酯复合水凝胶。通过反应条件、交联剂的含量、单体的浓度进行水凝胶合成方法筛选;通过一系列表征评价水凝胶的形貌学特征、结构学特征、溶胀性能、降解性能、内皮细胞相容性能。本论文进行单体的合成反应及表征评价,巯基壳聚糖的合成实验中显示,改变巯基乙酸与壳聚糖的配比、反应时间及碳化二亚胺的用量可以控制巯基壳聚糖的巯基度,本实验中筛选出的巯基化壳聚糖的反应条件为:反应体系pH=5.0,EDC浓度0.3mol/L,巯基乙酸与壳聚糖的物料比(质量比)为1:1,反应时间为10h;聚乙二醇二丙烯酸酯合成实验中显示,在三乙胺和氩气保护体系下进行丙烯酰氯及聚乙二醇的合成反应,经过红外检测及核磁共振氢谱检测证实产物合成成功。本论文进行水凝胶合成条件筛选,通过反应条件、单体浓度、交联剂用量等方面进行筛选,并通过成胶条件筛选出TCS-PEGDA复合水凝胶反应条件如下:巯基壳聚糖(TCS)浓度为:20mg/mL,聚乙二醇二丙烯酸酯(PEGDA)浓度为:100mg/mL,过硫酸铵(APS)浓度为:20mg/mL,四甲基乙二胺(TMEDA)用量为20μL。本论文对TCS-PEGDA(TP)复合水凝胶进行性质与特性表征,水凝胶形貌学实验证实随着PEGDA含量增加,凝胶内孔隙率越低,材料越致密;水凝胶FTIR实验证实合成水凝胶存在特征基团,实验成功制备TP水凝胶;水凝胶溶胀性能实验证实随着PEGDA含量增加,水凝胶溶胀性能降低;水凝胶降解性能实验证实随着PEGDA含量增加,水凝胶降解速率逐渐平缓,且TP2样品组降解速率明显高于其他三组;内皮细胞黏附实验表明水凝胶具有良好细胞相容性,随着巯基壳聚糖增加,细胞黏附性能越好;HE染色实验表明细胞可以从凝胶表面迁移到凝胶内部。综上所述,本论文成功合成巯基壳聚糖与聚乙二醇二丙烯酸酯复合水凝胶,并对形貌学特征、结构学特征、溶胀性能、降解性能、内皮细胞相容性能进行评价,最后得出TP4复合水凝胶组具有较好的溶胀性能、降解性能和内皮细胞相容性。
[Abstract]:Coronary heart disease, as one of the most common cardiovascular diseases, has become a serious threat to human health. At present, the most effective method in clinic is interventional therapy, that is, the placement of vascular stents in the diseased areas to smooth the previously blocked blood vessels. However, Stent is easy to cause vascular wall injury when it is implanted and opened, resulting in damage of intimal layer, which leads to complications such as restenosis and thrombus. Recently, researchers at home and abroad have mainly studied the biofunctional construction on the surface of stent. The stent can quickly form a layer of endothelium after implantation, and accelerate the repair and reconstruction of the injured endodermis, thus solving the problem of postoperative complications. In this paper, dopamine coating was deposited on the surface of titanium foil. Mercapto chitosan / polyethylene glycol diacrylate composite hydrogels were deposited. The hydrogel synthesis methods were screened by reaction conditions, crosslinking agent content and monomer concentration. The morphologic characteristics of hydrogels were evaluated by a series of characterization. In this paper, the monomer synthesis reaction and characterization evaluation showed that the ratio of thioglycolic acid and chitosan was changed. The reaction time and the amount of carbodiimide can control the sulfhydryl degree of mercapto chitosan. The reaction conditions of mercapto chitosan were as follows: the concentration of EDC was 0.3 mol / L, the ratio of thioglycolic acid to chitosan was 1: 1, the reaction time was 10 h, and the synthetic experiment of polyethylene glycol diacrylate showed that the concentration of EDC was 0.3 mol / L, the ratio of mercaptoacetic acid to chitosan was 1: 1 and the reaction time was 10 h. The synthesis of acryloyl chloride and polyethylene glycol in the system of triethylamine and argon was confirmed by IR and NMR. In this paper, the conditions of hydrogel synthesis were screened, and the reaction conditions were obtained. The concentration of monomer and the amount of crosslinking agent were selected. The reaction conditions were as follows: the concentration of thioglycol-chitosan was 20 mg / mL, the concentration of polyethylene glycol diacrylate was 100 mg / mL, the concentration of ammonium persulfate was 20 mg / mL, and the dosage of tetramethyl ethylenediamine was 20 渭 L. the reaction conditions were as follows: the concentration of mercaptochitosan was 20 mg / mL, the concentration of polyethylene glycol diacrylate was 100 mg / mL, the concentration of ammonium persulfate was 20 mg / mL, and the dosage of tetramethyl ethylenediamine was 20 渭 L. The properties and properties of TCS-PEGDA-TP-based hydrogels were characterized. Hydrogel morphology experiment confirmed that with the increase of PEGDA content, the lower the porosity of the gel, the denser the material, the more dense the hydrogel was, the more characteristic groups existed in the synthetic hydrogel, and the TP hydrogel was successfully prepared by the hydrogel FTIR experiment. The swelling property of hydrogel decreased with the increase of PEGDA content, and the degradation rate of hydrogel decreased with the increase of PEGDA content. The degradation rate of TP2 sample group was significantly higher than that of the other three groups, and the endothelial cell adhesion test showed that the hydrogel had good cytocompatibility, and with the increase of mercapto chitosan, The better the cell adhesion was, the better the HE staining showed that cells could migrate from the surface of the gel to the inside of the gel. In summary, the mercapto chitosan and polyethylene glycol diacrylate hydrogels were synthesized successfully, and the morphologic characteristics of the hydrogels were analyzed. The structural characteristics, swelling properties, degradation properties and endothelial cell compatibility were evaluated. Finally, the results showed that the TP4 composite hydrogels had better swelling, degradation and endothelial cell compatibility.
【学位授予单位】：西南交通大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R318.08

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