载有纳米银的新型复合补片的研制及应用

发布时间：2018-04-26 04:33

本文选题：纳米银 + 复合补片　；参考：《中国人民解放军医学院》2015年博士论文

【摘要】：目的与背景腹壁疝及腹壁缺损是临床常见病、多发病,仅北京地区每年发病约为8000-10000例。疝修补材料的出现使腹壁疝及缺损的修补达到了无张力的要求,从而使术后的复发率大大降低。目前临床常用的疝修补材料主要有以下3种：1、传统的单一成分的非吸收材料补片,如聚丙烯、聚酯、聚四氟乙烯等；2、复合材料补片,如强生的Proceed补片(聚丙烯、聚二氧六环酮、氧化再生纤维素)、巴德的Composix补片(聚丙烯、聚四氟乙烯)；3、生物补片,如COOK公司的SIS补片(猪小肠粘膜下层)等。但现有的补片材料均未达到“理想补片”的要求,即“足够的机械强度、稳定的化学性质、无致癌性、易于消毒灭菌、有限的异物反应、抗感染”。聚丙烯补片会引起机体强烈的炎症反应,可造成腹腔严重粘连、脏器穿孔、腹壁麻木、异物感；聚酯及聚四氟乙烯与机体的相容性差,且完全不能耐受细菌感染；生物补片的机械强度又为临床医生所担忧,且最为重要的是现在没有一种疝修补材料能够主动抗菌,能在污染和感染创面进行应用。而污染和感染情况下的腹壁缺损在战创伤、交通伤、同时进行肠道手术等情况下非常常见,目前对此类腹壁缺损多是一期清创、二期再以材料行确定性腹壁修补,不仅延长了治疗时间,给患者造成较长时间的痛苦,而且造成了卫生经济、社会劳动力的损失。要解决以上难题,就必须将杀菌剂引入到疝修补材料中。纳米银是直径在1～100nm的微小颗粒,具有量子效应、小尺寸效应和极大的比表面积,使之成为抗菌作用高效、持久的新型抗菌材料。目前纳米银在静脉导管、伤口敷料、人工血管、内固定架等方面均有应用。如果将纳米银结合于复合补片则可能会制出疝外科医生一直追求的“理想补片”。材料与方法第一部分载有纳米银的新型复合补片的构建及相关性质检测1、将不同浓度的纳米银溶液与聚丙交己内酯相结合,制成三种不同浓度的纳米银-聚丙交己内酯-聚丙烯复合补片。2、将以上三种不同浓度的纳米银复合补片进行体外抗菌及抑菌实验,筛选出最佳抗菌效果、最低浓度的纳米银复合补片。3、确定最佳浓度补片后,与普通复合补片对照,检测其拉伸性能及柔软度。第二部分载有纳米银的复合补片的浸提液对人成纤维细胞增殖的影响1、于体外模拟生理环境下纳米银复合补片中纳米银的释放规律。2、体外培养、鉴定人成纤维细胞。3、将不同时间点的纳米银补片浸提液加入至人成纤维细胞培养液中,观察对成纤维细胞生长的影响。第三部分载有纳米银的新型复合补片修补清洁及感染腹壁缺损的动物实验研究1、制作清洁及感染情况下大鼠腹壁缺损模型；2、以纳米银复合补片、聚丙烯补片、普通复合补片修补清洁及感染情况下的大鼠腹壁缺损,观察以下指标。2.1大体情况。2.2术后7d时伤口愈合情况。2.3感染创面中术后1d、3d、7d、14d、21d时各补片组的创面细菌计数。2.4术后21d时的腹腔粘连情况评分。2.5病理HE染色。2.6 TUNEL法检测创面及周边细胞的凋亡,并行定量分析。2.7免疫组化检测TGF-β1、IL-6、CD34的表达,并行定量分析。2.8免疫荧光检测PCNA表达,并行定量分析。2.9天狼猩红染色观察胶原表达,并行定量分析。结果1、成功合成了载有纳米银的新型复合补片,并选定0.5%浓度的纳米银复合补片即具有良好的抗菌效果。2、纳米银复合补片较普通复合补片在拉伸性能和柔软度方面无明显差异。3、纳米银复合补片中的纳米银释放随时间逐渐增加,在术后120h释放可达总载银量的98.76%,此时对人成纤维细胞增殖的抑制最为显著,但成纤维细胞依然能够贴壁生长。4、分别以纳米银复合补片、聚丙烯补片、普通复合补片修补清洁及感染大鼠腹壁缺损后,发现纳米银复合补片修复的腹壁缺损具有更少的细菌定植及伤口感染,更少的腹腔粘连,更少的腹壁瘢痕组织形成。结论新型的纳米银复合补片拥有抗感染能力,且具备稳定的理化性质,还能够促进创面的愈合、减少瘢痕形成。
[Abstract]:Objective and background abdominal wall hernia and abdominal wall defect are common clinical diseases. There are more than 8000-10000 cases of common disease in the region. The occurrence of hernia repair material makes the repair of abdominal wall hernia and defect reach the requirement of tension free, and the recurrence rate after operation is greatly reduced. The main clinical herniorrhaphy materials are 3 types: 1, Traditional single component non absorbing material patch, such as polypropylene, polyester, polytetrafluoroethylene, etc.; 2, composite patch, such as Johnson's Proceed patch (polypropylene, poly (two oxygen six cycloone, regenerated cellulose), Bard's Composix patch (polypropylene, polytetrafluoroethylene); 3, biological patch, such as COOK company's SIS patch (pig small intestinal mucosa submucosa) But the existing patch materials have not reached the requirements of "ideal patch", that is, "sufficient mechanical strength, stable chemical properties, no carcinogenicity, easy disinfection and sterilization, limited foreign body reaction, anti infection". Polypropylene patch will cause the body's strong inflammatory reaction, can cause severe abdominal adhesion, organ perforation, abdominal wall numbness and difference. Sense of substance; polyester and polytetrafluoroethylene are poorly compatible with the body and are completely incompatible with bacterial infection; the mechanical strength of the biological patch is also concerned by clinicians, and most important is that no herniorrhaphy can be active and can be used for contamination and infection, and the abdominal wall in the case of contamination and infection. The defect is very common in the situation of war trauma, traffic injury, and intestinal surgery. At present, most of this kind of abdominal wall defect is a stage debridement, and the two stage is repaired with the material with definite abdominal wall. It not only prolongs the time of treatment, causes the sufferers longer pain, but also makes the health economy and the loss of the social labor. To solve the problem, we should solve the problem The fungicides must be introduced into the herniorrhaphy. Nano silver is a small particle with a diameter of 1 to 100nm, with a quantum effect, small size effect and a great specific surface area, making it a new type of antibacterial material with high efficiency and lasting antibacterial effect. If the nano silver is combined with the composite patch, the "ideal patch" which the hernia surgeon has been pursuing is likely to be made by the hernia surgeon. The first part of the materials and methods contains the construction of a new composite patch of nano silver and the detection of the related properties 1, which combines the nano silver solution of different concentrations and polyprolactone, and makes three different kinds of differences. The concentration of nano silver polyprolactone polypropylene composite patch.2, the antibacterial and bacteriostasis experiment of the three different concentrations of nano silver composite patch in vitro was carried out. The best antibacterial effect and the minimum concentration of nano silver composite patch.3 were screened out, and the optimum concentration patch was determined, and the tensile properties and softness of the composite patch were compared with the common compound patch. Soft degree. The effect of the second part of the compound patch containing nano silver on the proliferation of human fibroblast 1, the release rule of nano silver in the nano silver composite patch in vitro simulated physiological environment.2, in vitro culture, identification of human fibroblast.3, and the nano silver patch extracts at different time points were added to human fibroblast culture. The effect of observation on the growth of fibroblast. Third experimental study on the repair of cleaning and infection of abdominal wall defect with a new composite patch with nano silver and 1, to make a model of abdominal wall defect in rats with clean and infected cases; 2, with nano silver composite patch, polypropylene patch, and common compound patch for cleaning and infection. Abdominal wall defect in rats, the following index.2.1 was observed. The wound healing in 7d after.2.2 operation, the wound bacteria count of 1D, 3D, 7d, 14d, 21d in.2.3 infected wounds was counted for.2.4 after.2.4. The expression of TGF- beta 1, IL-6 and CD34 was detected by immunohistochemistry, the expression of PCNA was detected by.2.8 immunofluorescence, and the expression of collagen was observed by.2.8 Sirius red staining, and the quantitative analysis was carried out. Results 1, a new composite patch containing nano silver was successfully synthesized, and the nano silver composite patch with 0.5% concentration had good resistance. The effect of bacterial effect.2, the nano silver composite patch has no significant difference in tensile property and softness of the composite patch.3, the release of silver nanoparticles in the nano silver composite patch increases with time, and the release of 120h can reach 98.76% of the total silver load after the operation, and the proliferation of human fibroblasts is most significant at this time, but the fibroblasts still can be used. .4, with nano silver composite patch, polypropylene patch, and common compound patch to repair and infect the abdominal wall defect of rats, found that the abdominal wall defect repaired by nano silver composite patch had less bacterial colonization and wound infection, less abdominal adhesion and less abdominal scar tissue. Conclusion new nano silver was found. The compound patch has the ability of anti infection and has stable physical and chemical properties. It can also promote wound healing and reduce scar formation.

【学位授予单位】：中国人民解放军医学院
【学位级别】：博士
【学位授予年份】：2015
【分类号】：R318.08

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