新型复合生物抗菌敷料的抗菌强度、吸湿能力及细胞毒性

背景：细菌感染是影响伤口愈合的主要因素之一,伤口渗出液里含有的大量炎症因子、蛋白酶和自由基都会减缓伤口的愈合速度。新型复合生物抗菌敷料的研发对治疗外科感染伤口有重要的意义,是创伤敷料发展的必然趋势。 目的：观察添加纳米银的海藻酸钙敷料的抗菌活性、吸湿能力及细胞毒性。 方法：将纳米银材料添加到海藻酸钙中制备新型复合生物抗菌敷料,并通过使用平板计数法、MTT法、电子显微镜观察法观察敷料的抗菌活性、吸湿能力及细胞毒性,再与银离子海藻酸钙敷料和海藻酸钙敷料进行对比,以期显示出新型复合生物抗菌敷料的具有强抗菌性及低细胞毒性的优势。 结果与结论：与银离子海藻酸钙敷料和海藻酸钙敷料相比,添加纳米银的新型复合生物抗菌敷料对金黄色葡萄球菌、铜绿假单胞菌均有更强的抑菌作用(P < 0.01),细胞毒性较低(P < 0.01);3种敷料的吸湿能力差异无显著性意义。证实此添加纳米银的海藻酸钙敷料的具有强抗菌性及低细胞毒性。      

纳米银抗菌凝胶细胞毒性的研究

目的 对纳米银抗菌凝胶的体外细胞毒性进行评价,为建立医用纳米材料生物评价体系提供依据.方法 采用MTT方法和琼脂覆盖法对纳米银抗菌凝胶的细胞毒性进行测试.结果 纳米银凝胶的细胞毒性与银含量和接触时间以及测试方法有关.结论 评价纳米医用材料的细胞毒性时需要考虑其用途、使用方式以及细胞毒性试验的方法等.     

细菌纤维素与纳米银复合制备创伤敷料

背景：近年来,采用纳米复合技术改良细菌纤维素赋予其新性能的研究越来越多。 目的：综述细菌纤维素与纳米银复合制备创伤敷料的方法。 方法：应用计算机检索2013年1月至2015年4月PubMed数据库及2007年1月至2015年4月CNKI数据库有关细菌纤维素、纳米银及其复合方式与应用的文献,检索词为“Bacterial Cellulose、Nano-silver,细菌纤维素、纳米银。” 结果与结论：制备细菌纤维素纳米银复合物的方式主要有溶液浸渍、原位复合及生物复合3种。溶液浸渍法可降低纤维矩阵中纳米银的离子浓度,使银离子释放高度可控,但遗传毒性及生物相容性有待测试。原位复合法减少了对纤维素网状结构的破坏,使银离子牢固地结合在其表面,减少对细胞的毒害作用,但使用的还原剂毒性较高,还原剂在纤维素内的残留问题不易解决。生物复合工艺中无有毒物质生成,对环境友好,合成的生物材料对人体产生的危害少且反应高度可控。 中国组织工程研究杂志出版内容重点：生物材料;骨生物材料; 口腔生物材料; 纳米材料; 缓释材料; 材料相容性;组织工程     

纳米银的抗菌特性及其在医学中的应用

纳米银是利用现代纳米技术制造的新一代抗菌材料,因其具有优异的抗菌杀菌活性及在伤口修复方面的积极作用,在医学生物学领域获得了广泛应用.目前已有一些纳米银产品应用于临床,如纳米银抗菌凝胶、纳米银敷料、纳米银心血管支架、纳米银导管、纳米银骨水泥等.近年来的研究表明,纳米银的长效、广谱、强效的抗菌活性源于其对微生物复杂而特异的抗菌机制.尽管纳米银不会使病菌产生耐药性,是人们期望中的理想抗菌材料,但研究人员对其毒性机制依然不甚了解.本文就纳米银的合成、抗菌机制、毒性及在医学中的应用做了简要总结和展望.     

医用钛合金Ti-6Al-4V基体/羟基磷灰石涂层复合材料的生物安全性评价

评价新型医用钛合金Ti-6Al-4V基体/羟基磷灰石涂层复合材料的生物安全性。通过遗传毒性试验、细胞毒性试验、骨植入实验和迟发型超敏试验,对Ti-6Al-4V基体/HA涂层复合材料进行安全性研究。该复合物试样在Ames实验中无诱变性,对体外CHL细胞不诱发染色体畸变,不引起体外V79细胞的基因突变,无体外细胞毒性。该检品在骨植入试验中,对局部组织无刺激。最大剂量试验法迟发型超敏试验显示,该检品无致敏性。该复合材料有良好的生物安全性。     

碳/碳复合材料的生物学安全性评价研究

目的 探讨碳/碳复合材料的生物学安全性.方法 依据中华人民共和国国家标准对医疗器械生物学评价的要求,对碳/碳复合材料进行细胞毒性试验、急性全身毒性试验、溶血试验、热源试验、肌肉植入试验等生物学安全性评价研究.结果 碳/碳复合材料的各项生物学性能指标符合国家标准要求,无细胞毒性和全身毒性、无热源性,具有良好的生物相容性....     

纳米羟基磷灰石急性毒性试验研究

对纳米羟幕磷灰石(nano-HAP)进行急性毒性试验研究,为长期毒性试验和其他毒理学试验提供参考依据,并初步了解nano-HAP进入血液循环系统后,是否会迁移到其它器官和组织.实验选用清洁级的110～130g Wistar大鼠70只,分为7组,实验组各组剂量分别为21.66mg/kg、29.97 mg/kg、41.49 mg/kg、57.42 mg/kg、79.48 mg/kg、110.39 mg/kg,以生理盐水为对照组.单次尾静脉注射,14d内观察动物的毒性症状,记录动物死亡情况.将死亡动物解剖,对动物主要脏器进行病理组织学检查.结果显示nano-HAP在Wistar大鼠身上尾静脉注射时LD50为51.79 mg/kg,由病理结果推测实验动物的死亡原因是由血管栓塞所致.在一只最低剂量组死亡动物肝的汇管区及附近肝内有占位性蓝染无定型物,肝内灶性炎细胞浸润.说明nano-HAP颗粒在充分分散的情况下会通过血液循环进入到身体其它器官,因此有必要对nano-HAP的生物安全性进行进一步研究.     

不同粒径银粒子的体外细胞毒性比较

目的 比较纳米银粉末与微米银粉末体外细胞毒性的差异,并初步探讨毒性机制与粒径大小的相关性.方法 四种不同粒径银粒子通过扫描电镜确定其粒径分布后,制备成不同浓度的含银培养液与L929细胞接触培养,通过倒置相差显微镜观察其形态,采取MTT（四唑盐）比色法量化细胞毒性,计算相对增值率（RGR）,并进行毒性评价.结果 当银浓度在一定范围内（2.5～25）μg//mL,纳米银粒子呈现轻微细胞毒性（0～1）级,RGR与含银量呈量-效关系;随着浓度增高到大于50μg/mL时,与之共培养的细胞,形态上发生较大改变,显示明显的细胞毒性,量-效相关性也随之消失.粒径较小的微米银在银浓度达到250μg/mL时显示明显的细胞毒性.而粒径较大的两组微米银粒子在所有试验浓度下,共培养的细胞生长良好,未见明显的细胞毒性.结论 粒径不同的银粒子的体外细胞毒性有较大差异.同等剂量下,纳米级的银粒子和粒径较小的微米级银粒子,比粒径较大的微米级银粒子的体外细胞毒性更大.     

纳米银溶胶的体外细胞毒性评价及其机制研究

目的 对纳米银溶胶的体外细胞毒性进行评价,初步探讨纳米银对细胞的毒性作用机制.方法利用化学还原法制备纳米银溶胶,通过紫外-可见分光光度计和透射电镜对其物理特性进行检测;以小鼠纤维肉瘤细胞( L929)为研究对象,通过细胞形态观察、LIVE/DEAD染色分析和MTT检测来评价纳米银对细胞的毒性作用;在电子显微镜下观察纳米...     

丙烯酰胺对雄陛生殖系统毒性影响的研究进展

近年来在淀粉质食品经高温处理时检出有丙烯酰胺的存在,其毒性再次受到广泛关注.已有资料显示:丙烯酰胺可能具有多种毒性.众多科研人员纷纷投入到丙烯酰胺的毒性研究中,并取得了一定的进展,但其毒性机制仍不完善;关于丙烯酰胺对于人类的影响,除了已明确有神经毒性外,其它毒性均有待于进一步的研究和探讨.本综述将重点关注丙烯酰胺对雄性生殖系统的毒性影响.     

The effect of particle size on the cytotoxicity, inflammation, developmental toxicity and genotoxicity of silver nanoparticles

Silver nanoparticles are of interest to be used as antimicrobial agents in wound dressings and coatings in medical devices, but potential adverse effects have been reported in the literature. The most pronounced effect of silver nanoparticles and the role of particle size in determining these effects, also in comparison to silver ions, are largely unknown. Effects of silver nanoparticles of different sizes (20, 80, 113 nm) were compared in in vitro assays for cytotoxicity, inflammation, genotoxicity and developmental toxicity. Silver nanoparticles induced effects in all endpoints studied, but effects on cellular metabolic activity and membrane damage were most pronounced. In all toxicity endpoints studied, silver nanoparticles of 20 nm were more toxic than the larger nanoparticles. In L929 fibroblasts, but not in RAW 264.7 macrophages, 20 nm silver nanoparticles were more cytotoxic than silver ions. Collectively, these results indicate that effects of silver nanoparticles on different toxic endpoints may be the consequence of their ability to inflict cell damage. In addition, the potency of silver in the form of nanoparticles to induce cell damage compared to silver ions is cell type and size-dependent.     

The influence of lysosomal stability of silver nanomaterials on their toxicity to human cells

How silver nanomaterials (Ag NMs) could induce toxicity has been debated heatedly by many researchers. We utilized Ag nanoclusters (Ag NCs) with the same size and ligand protection but different core surface speciation. Ag⁺-rich NCs (Ag⁺-R NCs) and their counterpart, the reduced Ag⁰-rich NCs (Ag⁰-R NCs) are synthesized to represent possible dichotomous stages in silver nanomaterial degradation process. Here we show Ag⁰-R NCs induce higher cellular toxicity when compared to Ag⁺-R NCs. This cellular toxicity is brought about via the modulation of reactive oxygen species (ROS) in cells as a result of the more rapid release of Ag species from Ag⁰-R NCs and subsequent oxidation into Ag⁺ in the lysosomal compartment. The weaker Ag⁰-R bond greatly potentiated the release of Ag species in the acidic and enzymatic processes within the lysosomes. Since lysosomes are absent in bacteria, increasing silver nanomaterials stability may lower toxicity in mammalian cells whilst not reducing their efficacy to fight bacteria; this redesign can result in a safer silver nanomaterial.     

Biological actions of silver nanoparticles embedded in titanium controlled by micro-galvanic effects

Titanium embedded with silver nanoparticles (Ag NPs) using a single step silver plasma immersion ion implantation (Ag-PIII) demonstrate micro-galvanic effects that give rise to both controlled antibacterial activity and excellent compatibility with osteoblasts. Scanning electron microscopy (SEM) shows that nanoparticles with average sizes of about 5 nm and 8 nm are formed homogeneously on the titanium surface after undergoing Ag-PIII for 0.5 h and 1 h, respectively. Transmission electron microscopy (TEM) and X-ray photoelectron spectroscopy (XPS) indicate that those nanoparticles are metallic silver produced on and underneath the titanium surface via a local nucleation process from the solid solution of α-Ti(Ag). The Ag-PIII samples inhibit the growth of both Staphylococcus aureus and Escherichia coli while enhancing proliferation of the osteoblast-like cell line MG63. Electrochemical polarization and Zeta potential measurements demonstrate that the low surface toxicity and good cytocompatibility are related to the micro-galvanic effect between the Ag NPs and titanium matrix. Our results show that the physico-chemical properties of the Ag NPs are important in the control of the cytotoxicity and this study opens a new window for the design of nanostructured surfaces on which the biological actions of the Ag NPs can be accurately tailored.     

Construction of antibacterial multilayer films containing nanosilver via layer-by-layer assembly of heparin and chitosan-silver ions complex

Antibacterial multilayer films containing nanosilver were prepared via layer-by-layer fashion. PET film was aminolyzed with 1,6-hexanediamine to introduce amino groups on PET film surface; chitosan-silver nitrate complex and heparin were alternately deposited onto an aminolyzed PET film surface, and subsequently, the silver ions within the multilayer films were reduced with ascorbic acid to form silver nanoparticles. UV-visible spectroscopy and transmission electron microscopy confirmed the formation of well-dispersed nanosilver particles with sizes (10-40 nm) that depended on the initial concentration of silver ions in chitosan solution and the pH of ascorbic acid solution. The chitosan/heparin multilayer films were possessed of bactericidal effect on Escherichia coli (E. coli), and this antibacterial effect could be significantly enhanced by the incorporation of silver nanoparticles into the multilayer films. The multilayer films containing nanosilver were not only effective as antibacterial but also as anticoagulant coating. And cell toxicity evaluation suggested that the multilayer films containing nanosilver did not show any cytotoxicity. The multilayer films containing nanosilver may have good potentials for surface modification of medical devices, especially for cardiovascular implants.     

Antibacterial silver-containing silica glass prepared by sol-gel method

Recently, various inorganic antibacterial materials containing silver have been developed and some of them are in commercial use. Colorless and more chemically durable materials which slowly release the silver ion for a long period are, however, desirable to be developed for medical applications such as composite resin for dental restoration. In the present study, Si(OC2H5)4, Al(NO3)3 x 9H2O, AgNO3, HNO3, C2H5OH and H2O solutions with various Al/Ag atomic ratios under a constant Si/Ag atomic ratio of 1/0.023 were kept at 40 degrees C for gelation and drying. Thus obtained gels were pulverized into fine powders with average particle size of approximately 10 microm and then heat-treated at 900-1000 degrees C for 2 h. For the composition Al/Ag = 0, a yellow-colored glass was formed, since the silver existed in the form of metallic colloids in the glass. However, for the compositions Al/Ag > or = 1, colorless glasses were successfully obtained, since the silver existed in the form of Ag+ ions in the glasses. For the composition Al/Ag = 0, the silver ions got released rapidly into the water, whereas, for the compositions Al/Ag > or = 1, they gradually got released into the water at a controlled rate. A composite of the obtained powders with Al/Ag atomic ratio of 1 with Bis-GMA/TEGDMA in 70:30 weight ratio showed excellent antibacterial property. The sol-gel derived silica glass powders containing silver with compositions Al/Ag > or = 1 are believed to be useful as an antibacterial material for medical applications such as filler of composite resin for dental restoration.     

Polyamide/silver antimicrobials: effect of filler types on the silver ion release

The efficiency of various silver-based antimicrobial fillers (elementary silver and silver substituted materials) in polyamide (PA) toward their silver ion (Ag+) release characteristics in an aqueous medium was investigated and discussed. Anode stripping voltammetry (ASV) was used for the quantitative estimation of Ag+ release from these composites. The biocidal (Ag+) release from the composites was found to be dependent on the time of soaking in water and the nature of the filler. The long-term Ag+ release capability of the elementary silver-based PA/Ag composite is promising compared with the commercial counterparts. The silver ion release potential of polyamide composites where the silver filling was performed by using supercritical carbon dioxide (scCO2) is also discussed. The composites release Ag+ at a concentration level capable of rendering antimicrobial efficacy and proved to be active against the microbes. A good agreement exists between the Ag+ release experiments and antimicrobial test results. The observed results on the influence of the nature of the filler and crystallinity on the biocidal release and the varying long-term release properties could be helpful in the design of industrially relevant biomaterials.     

Antibacterial nano-structured titania coating incorporated with silver nanoparticles

Titanium (Ti) implants are widely used clinically but post-operation infection remains one of the most common and serious complications. A surface boasting long-term antibacterial ability is highly desirable in order to prevent implant associated infection. In this study, titania nanotubes (TiO(2)-NTs) incorporated with silver (Ag) nanoparticles are fabricated on Ti implants to achieve this purpose. The Ag nanoparticles adhere tightly to the wall of the TiO(2)-NTs prepared by immersion in a silver nitrate solution followed by ultraviolet light radiation. The amount of Ag introduced to the NTs can be varied by changing processing parameters such as the AgNO(3) concentration and immersion time. The TiO(2)-NTs loaded with Ag nanoparticles (NT-Ag) can kill all the planktonic bacteria in the suspension during the first several days, and the ability of the NT-Ag to prevent bacterial adhesion is maintained without obvious decline for 30 days, which are normally long enough to prevent post-operation infection in the early and intermediate stages and perhaps even late infection around the implant. Although the NT-Ag structure shows some cytotoxicity, it can be reduced by controlling the Ag release rate. The NT-Ag materials are also expected to possess satisfactory osteoconductivity in addition to the good biological performance expected of TiO(2)-NTs. This controllable NT-Ag structure which provides relatively long-term antibacterial ability and good tissue integration has promising applications in orthopedics, dentistry, and other biomedical devices.     

DNA damage induced by micro- and nanoparticles--interaction with FPG influences the detection of DNA oxidation in the comet assay

Reliable methods for evaluation of toxicity from particles, such as manufactured nanoparticles, are needed. One promising tool is the comet assay, often used to measure DNA breaks (strand breaks and alkali-labile sites) as well as oxidatively damaged DNA, the latter by addition of specific DNA repair enzymes such as formamidopyrimidine DNA glycosylase (FPG). The aim of this study was to investigate the use of the comet assay for analysis of DNA oxidation by a range of micro- and nanoparticles in the lung cell lines A549 and BEAS-2B and to test the hypothesis that nanoparticles present in the cells during the assay performance may interact with FPG. This was done by investigating the ability of micro- and nanoparticles (stainless steel, subway particles, MnO(2), Ag, CeO(2), Co(3)O(4), Fe(3)O(4), NiO and SiO(2)) to induce DNA breaks, oxidatively damaged DNA (FPG sites, dominantly 8-oxoguanine), intracellular production of reactive oxygen species (ROS) and non-cellular oxidation of the DNA base guanine, as well as by studying interactions of the particles and their released ions with FPG. Several particles caused DNA breaks, but low levels of FPG sites. The ability of FPG to detect DNA oxidation induced by a photosensitiser was however shown. An oxidative capacity of the particles was indicated by increased levels of intracellular ROS, and especially Ag and subway particles caused non-cellular oxidation of guanine. Incubation of FPG with the particles led to less FPG activity, particularly with nanoparticles of Ag but also with CeO(2), Co(3)O(4) and SiO(2). Further investigations of these particles revealed that for Ag, the decreased activity was mainly due to released Ag ions, whereas for CeO(2) and Co(3)O(4), FPG interactions were due to the particles. We conclude that measurement of oxidatively damaged DNA in cells exposed to nanoparticles may be underestimated in the comet assay due to interactions with FPG.     

Preparation of antibacterial silver-doped silica glass microspheres

Various types of inorganic substances doped with silver ions have been developed as antibacterial materials, and some have already been commercialized. Colorless and chemically durable materials that slowly release silver ions are, however, still need to be developed. The present authors have previously shown that when a silica glass doped with silver and aluminium ions is prepared using the sol-gel method, the resultant product is colorless, chemically durable, and slowly releases silver ions into water over a long period. The doped silica glass takes a form of microspheres <1 microm in diameter, it is easily mixed with organic polymers, and the mixture can be formed into a thin film or fine fibers, etc. We report on the preparation of silver doped silica glass microspheres having a diameter =1 microm, using the sol-gel method. Initially, tetraethoxysilane was partially prehydrolyzed by water in ethanol, and then aluminium triisopropoxide was added to the solution to form Si-O-Al bonds. Finally, an ammonia solution containing silver nitrate was added to form silica microspheres doped with silver ion together with aluminium ions. The results show monodispersed microspheres 0.4-0.6 microm in diameter were obtained with nominal compositions of Si/Al/Ag = 1/0.01-0.03/0.003-0.03, with a molar ratio of Al/Ag = 1-3.3. The microspheres were colorless, showed a high chemical durability, and slowly released silver ions into water at 37 degrees C. Microspheres with the composition Si/Al/Ag = 1/0.01/0.01 showed excellent antibacterial activity against Escherichia coli. The minimum inhibitory concentration (MIC) of the microspheres was 400, which is less than the MIC value (800) of commercial antibacterial materials.     

Synergistic effects of dual Zn/Ag ion implantation in osteogenic activity and antibacterial ability of titanium

Zinc (Zn) and silver (Ag) are co-implanted into titanium by plasma immersion ion implantation. A Zn containing film with Ag nanoparticles (Ag NPs) possessing a wide size distribution is formed on the surface and the corrosion resistance is improved due to the micro-galvanic couples formed by the implanted Zn and Ag. Not only are the initial adhesion, spreading, proliferation and osteogenic differentiation of rBMSCs observed from the Zn/Ag implanted Ti in vitro, but also bacteria killing is achieved both in vitro and in vivo. Electrochemical polarization and ion release measurements suggest that the excellent osteogenic activity and antibacterial ability of the Zn/Ag co-implanted titanium are related to the synergistic effect resulting from the long-range interactions of the released Zn ions and short-range interactions of the embedded Ag NPs. The Zn/Ag co-implanted titanium offers both excellent osteogenic activity and antibacterial ability and has large potential in orthopedic and dental implants.