单宁酸对经戊二醛固定的牛心包改性研究

发布时间：2018-08-07 13:11

【摘要】：目前商业上用于替换心脏瓣膜手术的人工心脏瓣膜主要两大类：生物瓣膜和机械瓣膜。机械瓣膜耐久性高,组织相容性差,植入人体后需要长期进行抗凝血治疗,否则易产生血栓。生物瓣血液动力学性能好,血栓形成的发生率较低,但耐久性较差且容易发生钙化。同种瓣膜作为一种生物瓣膜,其组织相容性良好,但来源有限且耐久性较差,这些缺点使同种瓣膜在临床应用上受到限制。异种生物瓣膜是临床上应用较广泛的生物瓣膜,对生物组织进行生化处理是目前国内外对异种生物瓣膜的主要研究内容。交联剂及其他处理方法的使用使生物瓣膜的耐久性有了较大的提高,生物材料的钙化现象也得到较大的改善。1968年,使用戊二醛对生物材料进行处理和保存,使生物材料在临床应用上得到突破性的进展。经戊二醛处理后,材料的耐久性大大提高,具有较高的机械强度,低免疫原性。但戊二醛处理后的材料存在细胞毒性,易钙化、衰败等缺点使生物材料的远期使用效果不佳。因此寻找一种更加理想的处理方案或交联剂对生物材料进行处理,从而制备出力学性能、组织相容性、血液相容性更加理想的心脏瓣膜变得尤为重要。制备异种瓣膜的生物材料有多种,例如猪心包或牛心包。其中牛心包是一种来源广泛,低免疫原性,组织相容性较好的生物材料。最理想的交联剂可以保存生物材料完整的组成成分和三维超微结构,并且提高材料的力学性能和生物学稳定性,但所有的交联剂都或多或少存在着缺陷。不同的交联剂对生物材料影响有很大的差别。本文使用一种新型环保低毒的交联剂联合传统的交联剂戊二醛对心包进行改性处理并在性能上进行比较,希望构建一种力学性能和生物学性能良好,具有良好生物相容性的异种生物瓣膜。主要研究内容如下： (1)采用不同浓度单宁酸联合戊二醛对牛心包处理,并对不同浓度的单宁酸联合戊二醛处理后的牛心包进行理化性质的评价,确定单宁酸联合戊二醛的最佳浓度。通过对外观、厚度、含水量、接触角、热皱缩温度、抗拉伸强度、弹性模量的测试和SEM扫描分析对单宁酸联合戊二醛处理牛心包的效果进行评价,并与戊二醛进行比较。经单宁酸处理后,牛心包厚度增加,韧性增强,呈褐色,接触角变小,热皱缩温度提高,抗拉伸强度增大,弹性模量提高,证明牛心包经单宁酸处理后材料的亲水性能提高,热力学稳定性和力学性能得到改善。SEM扫描结果表明：牛心包经3%单宁酸处理后,纤维排列紧密、规则优于其他处理组。根据各组单宁酸处理牛心包后理化性质的结果,3%为处理牛心包的最佳单宁酸浓度。 (2)采用3%单宁酸联合戊二醛对牛心包进行处理,并探究且生物化学稳定性,由于单宁酸本身的涩性,能与蛋白质结合,能使生物体内原生质凝固,本文针对单宁酸联合戊二醛对牛心包处理后的胶原蛋白和弹性蛋白的含量变化,以及处理后牛心包的抗酶解能力进行了探究。结果显示,单宁酸联合戊二醛处理后的牛心包胶原蛋白含量和弹性蛋白含量得到了保护,与戊二醛组比较减少弹性蛋白的流失,与上文提到的弹性模量的提高结果吻合。抗酶解能力也显著增强,证明单宁酸联合戊二醛处理后的牛心包后在生物化学稳定性方面得到改善。体外细胞毒性检测和溶血性能检测结果表明,单宁酸联合戊二醛处理的牛心包与戊二醛处理的牛心包有较低的细胞毒性,溶血率较低。细胞毒性级数为1级,几乎无毒性,且溶血率较低。本实验结果证明,3%单宁酸联合戊二醛处理的牛心包在力学性能,生物相容性方面得到了极大的改善。
[Abstract]:At present, there are two main types of artificial heart valves in commercial replacement of heart valve surgery: biological valves and mechanical valves. Mechanical valves have high durability and poor histocompatibility. They need long-term anticoagulant therapy after implantation, otherwise thrombus is easy to produce. The same valve, as a biological valve, is a biological valve with good histocompatibility, but limited source and poor durability. These defects have limited the clinical application of the same valve. The biological valve is a widely used biological valve, and the biochemical treatment of biological tissue is currently in the country. The main research content of the alien biological valve. The use of crosslinking agent and other treatment methods made the durability of biological valve improved greatly. The calcification of biological materials has been greatly improved in.1968 years. The use of glutaraldehyde to treat and preserve biological materials make biological materials breakthrough in clinical application. Progress. After treated with glutaraldehyde, the durability of the material is greatly improved, with high mechanical strength and low immunogenicity. However, the defects of the materials treated with glutaraldehyde have the disadvantages of cytotoxicity, easy calcification, decay and so on, so as to find a more ideal treatment scheme or cross-linking agent for biological materials. The heart valves are particularly important in preparing mechanical properties, histocompatibility, and ideal blood compatibility. There are many biological materials for the preparation of dissimilar valves, such as the porcine pericardium or the bovine pericardium. The bovine heart bag is a biological material with wide sources, low immunogenicity and good histocompatibility. The ideal crosslinker is the best possible agent. To preserve the complete composition and the three-dimensional ultrastructure of the biomaterials, and to improve the mechanical and biological stability of the materials, all the crosslinker has more or less defects. The effects of different crosslinker on biological materials are very different. Modifying the pericardium by modified glutaraldehyde and comparing its properties, we hope to construct a kind of biocompatible biological valve with good mechanical and biological properties and good biocompatibility. The main contents are as follows:
(1) use different concentration of tannic acid and glutaraldehyde to treat bovine pericardium, and evaluate the physical and chemical properties of different concentration of tannic acid and glutaraldehyde, and determine the optimum concentration of tannic acid and glutaraldehyde. Through the appearance, thickness, water content, contact angle, thermal shrinkage temperature, tensile strength and modulus of elasticity The effects of tannic acid and glutaraldehyde were evaluated and compared with glutaraldehyde, and compared with glutaraldehyde. After tannic acid treatment, the thickness of the cow's heart was increased, the toughness was increased, the contact angle was smaller, the temperature of the heat shrinkage was increased, the tensile strength increased and the modulus of elasticity increased, which proved that the cow heart bag was treated with tannic acid after treatment. The hydrophilic properties of the material were improved, the thermodynamic stability and mechanical properties were improved by.SEM scanning. The results showed that after 3% tannic acid treatment, the fiber was arranged closely and the rules were better than the other treatment groups. According to the results of the physicochemical properties of the heart bag treated with tannic acid, 3% was the best tannic acid concentration in the cow's heart bag.
(2) using 3% tannic acid and glutaraldehyde to treat the bovine heart bag, and explore and be biochemical stability. Because of the astringency of tannic acid itself, it can combine with protein to solidify the protoplasm of the organism. In this paper, the content changes of the collagen and elastin after the treatment of the bovine heart bag with tannic acid and glutaraldehyde and after treatment are treated. The anti enzymatic ability of the bovine pericardium was explored. The results showed that the content of Niu Xinbao collagen and the content of elastin after tannic acid combined with glutaraldehyde were protected, and the loss of elastin was reduced with the glutaraldehyde group, which was in agreement with the increase of the modulus of elasticity mentioned above. The biochemical stability of the bovine pericardium treated with ningic acid and glutaraldehyde was improved. The cytotoxicity test and hemolytic test in vitro showed that the bovine pericardium treated with tannic acid and glutaraldehyde had lower cytotoxicity and lower hemolysis rate. The cytotoxicity progression was 1 and almost non-toxic. The results of the experiment show that 3% tannic acid combined with glutaraldehyde has greatly improved the mechanical properties and biocompatibility.
【学位授予单位】：东华大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R318.08

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