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中空活性炭纤维—纳米银复合敷料的研制及初步实验研究
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摘要
一、研究背景
     创面的处理关系着外科手术治疗的成败,而突发事件,如地震、火灾,军事战争或偏远山区,由于存在现场救治条件相对简陋,外界环境复杂,后送时间长等多重因素,更加凸显了创面保护和治疗的重要意义。因此国内、外专家长期致力于预防创面感染、治疗难治性感染创面、加快创面愈合的研究,其中有关创面敷料的研究也是烧伤、整形外科众多研究热点中的焦点之一。
     随着对伤口愈合研究机制的深入,人们认识到使用敷料的目的远远不止是为了覆盖创面,还应具有吸附分泌物、杀灭细菌和促进伤口愈合的多重功效。当前国际公认的理想创面敷料应具备以下特点:(1)保护创面且减少创面分泌物,更换次数少;(2)为创面愈合提供良好的局部环境,抗感染能力强,能促进创面愈合;(3)无免疫抗原性;(4)无细菌耐药性;(5)易制备、易储存及重复利用可能。
     近年来生物科学技术和材料加工业取得了长足进步,使得伤口敷料也发生了革命性的变化,从传统纱布敷料、生物敷料、生长因子敷料到组织工程创面覆盖物等等,尽管种类琳琅满目,但是或多或少的都存在一定缺陷:如传统纱布,价钱便宜,无促进伤口愈合和抑制创面细菌作用;生物敷料,根据其合成原料又可分为若干种,有一定加快愈合作用,但无法抑制细菌,且来源受限;组织工程创面覆盖物,是一种接近理想要求的敷料,生产成本昂贵,价格过高,长期使用患者难以承受,因此限制了它的推广和应用。由此可见,研制一种新型的创面敷料以符合临床工作需要,显得迫在眉睫。
     因此,我们紧密结合当今世界医用纳米材料研究的主流方向,利用了纳米材料所特有的表面效应、小尺寸效应和宏观量子隧道效应,与其它多门学科相互合作,研制出中空活性炭纤维-纳米银复合敷料,该敷料兼具了多种医用敷料的优点,包括吸附性强、抗张强度大、生物适应性好、抑制创面细菌生长、促进创面愈合、价格低廉、储存条件简易等。本课题所研究的成果,不仅可以服务于临床日常工作需要,而且在军事战争、灾害及贫困地区也能得到广泛的应用。且目前未见国内、外有关中空活性炭纤维与纳米银两者相结合服务于临床应用的研究报道。
     二、研究目的
     1、明确中空活性炭纤维-纳米银复合敷料的制备方法,观察大体和显微结构,测定材料学性能。
     2、通过初步动物实验了解中空活性炭纤维-纳米银复合敷料对感染创面的治疗效果及安全性,包括研究其抑制感染创面细菌作用及促进创面愈合的能力,为今后应用于临床提供有力的实验依据。
     三、研究内容和方法
     1、中空活性炭纤维-纳米银复合敷料的制备:碳化法制备活性炭纤维;液相法制备纳米银;加入硅铝酸盐分子筛载体通过综合纺纱完成敷料制备。
     2、扫描电镜(SEM)观察显微结构特征;应用扫描隧道显微镜(STM),UV-2450型紫外一可见光分光光度计,x Pert PRO x射线粉末衍射仪,FEI Tecnai G 20透射电镜,ASAP22400自动物理吸附仪等测定材料各项性能及表征。
     3、动物实验:建立感染创面模型;根据不同创面处理方式分为三组(实验组:中空活性炭纤维-纳米银复合敷料,对照组一爱可欣辅料、对照组二新霉素溶液辅料),常规换药,定期做创面细菌培养并计数以及切取组织样本,对比创面愈合、控制感染方面的疗效及中空活性炭纤维-纳米银复合敷料的安全性。
     四、研究结果
     1、中空活性炭纤维-纳米银复合敷料的大体形态与传统纱布相近。显微结构显示纤维排列有序,孔径较均匀,为7μm-10μm之间;硅铝酸盐无机分子筛载体装载纳米银颗粒结构致密,粒径均匀,在30nm-40nm之间,而纳米银粒径在5nm左右,表面原子释放银离子可达70%。
     2、吸附、脱附实验证实敷料能重复利用,降低医疗成本;弹性模量、拉伸强度、断裂伸长率等力学指标远远高于传统棉质敷料,表明该敷料抗张、耐磨性质优越;敷料因管道纤维的存在,沿纤维长径水平散热模式强于垂直散热模式,改变了使用一般敷料创面的局部散热方式,在发挥其吸附过滤作用的同时还可以保持创面一定温度。
     3、创面细菌培养计数结果表明第5d、9d、13d及17d的细菌累计抑制率,实验组较对照组一和二明显提高。经创面直接观察和病理组织切片观察,发现实验组创面比对照组一和二用药后创面愈合时间提前3~5天,伤口愈合时间明显提前,且实验组创面边缘成纤维细胞、胶原纤维等增殖明显多于对照一组和对照二组。未见局部致敏和全身症状。五、结论
     本课题设计制备的中空活性炭纤维-纳米银复合敷料,工艺流程较简单,能够重复利用,降低医疗成本,且抗张、耐磨性质优越,生物体使用安全性高,有良好的散热模式,辅助调节创面温、湿度,其强大的吸附、过滤功能,使得应用范围更加广泛;初步动物实验验证该敷料对感染创面SA和EC的抑制率在起效时间和强度方面,以及促进创面愈合时间、加快上皮细胞增殖方面与其他敷料相比均表现出明显的优势,是目前临床上较为理想的创面敷料。
Background
     Emergency trauma and postoperative wounds in patients with treatment is related to success or failure of surgical treatment,and unexpected events,such as earthquake, fire disaster, military war or remote mountain areas,because of existing multiple factors,like that,the relatively primitive conditions at the scene for medical treatment,complexity of the external environment,long time to transport,so,the significance of the wound protection and treatment is more important. For this reason,most domestic and foreign experts go in for studing prevention of wound infection,the treatment of refractory wound infection,accelerate wound healing for long time. One of the researches related to wound dressings is also one hot spot of a large number of research focus in Burn Surgery and Plastic Surgery.
     With the development study of wound healing mechanism,people found the purpose of using wound dressing is not only cover wound surface but also refrain bacterium and promote wound surface healing.There have great improvement of biotechnology and industry technology in recent years,and great changes have happened from tradition gauze dressing, biological dressing,synthetic dressing and organize engineering dressing. Although the types have a vast array of beautiful and fine things,all more or less defects must exist,such as traditional gauze which is inexpensive,without the promotion of wound healing and inhibition of wound bacteria;biological dressing,in accordance with its synthesis of raw materials can be divided into a number of species, can speed up the healing,but unable to kill the bacterial and source is limited;organize engineering dressing,is close to the ideal requirements of dressings,because of expensive production costs and higher price,long-term using is unbearable in patients, thereby its promotion and application is limited.
     This topic studies the development of hollow activated carbon fiber - nanosilver composite dressings manufactured by mutual cooperating of many subjects,in close connection with medical research mainstream direction of the nano-materials in the world,using of nano-materials’specific,like that,the surface effect,small size effect and macroscopic quantum tunneling effect,to be provided with a wide range of medical dressing advantages,including strong adsorption,large tensile strength, good biocompatibility, inhibiting bacterial growth,promoting wound healing, low cost,simple storage conditions. This issue and the results of research can not only serve the clinical, but also in the military war, disasters and poverty-stricken areas,to gain a wide range of applications. Furthermore,there is not study report currently concerned with the hollow activated carbon fiber and nano-silver combinated to service clinical application at the domestic or abroad.
     Objective
     1.Preparation of hollow activated carbon fiber - nanosilver composite dressings, observation of the general and microstructur,determination of nanomaterials’unique properties applicable to Medicine.
     2.Learn the therapeutic effect and safety through the animal experiments of hollow activated carbon fiber - Nanosilver dressing on infected wounds (depth of the deep dermis),including its role in inhibiting bacterial infection in the wound and promote wound healing capacity to provide strong experimental evidence for clinical application in the future.
     Contents and methods
     1.Hollow activated carbon fiber-nanosilver composite dressing preparation:carbonize for preparation of activated carbon fiber;liquid Preparation of nanosilver;add al- uminosilicate molecular sieve carrier,complete dressing preparation by integrated spinning.
     2.Scanning electron microscopy (SEM) observation of the microstructure charac- teristics;application of scanning tunneling microscope (STM),UV-2450 UV Visible Spectrophotometer,x Pert PRO x-ray powder diffraction instrument,FEI Tecnai G 20 TEM and ASAP22400 Automatic physical ad- sorption instrument to determinate of the properties and characterization of materials.
     3.Animal experiments:set up the wound infection model;designed three test groups,conventional dressing,regularly cut tissue samples,com- parison the efficacy of wound healing, infection control aspects and the security of using hollow activated carbon fiber-nanosilver composite dressing.
     Results
     1.General shape of hollow activated carbon fiber-nanosilver composite dressing is similar to traditional gauze,microstructure fibers arranged in an orderly,more uniform length and diameter,aspect ratio to 500:1,aperture 20nm-35nm,length 100μm-150μm,wall thickness 10nm;nano-silver compact structure,particle diameter 5nm.
     2.Fiber tensile strength than steel with high-volume 100-fold,weight of the latter 1 / 6-1 / 7;silver-containing surface area before and after no significant change;nano-silver ion release of nearly 70%.
     3.The production of animal models of wound infection from postoperative day 1 every 4 days from determination of a bacterial count, results show that the first 5d, 9d, 13d and 17d of bacteria accumulated inhibition rate, the experimental group than the control group I and II markedly improved. Direct observation by the wound tissue and pathological observations, found that the experimental group than the control group, wound one and two hours after administration of wound healing ahead of schedule 3 ~ 5 days, wound healing time was significantly ahead of schedule. Detection of heavy metals on animal blood had no significant abnormalities, no local and systemic allergic symptoms.
     Conclusion
     It has great applicate scopes because of many features,such as slick,moisten,and can make various kinds shapes according to wound surface’s position and size, and have the ability reduce invation of bacterium in wound surface.The inhibiton ration of Nbbcd outweigh other two groups to SA and EC.Nbbcd have the better bacteriostatic action and ability of promote wound surface healing compare with other dressings.All in all,it is the ideal wound dressing in clinical at present.
引文
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