高分子材料的表面菌膜

背景:医疗器械尤其是高分子介入性导管引起的导管相关型感染是院内感染的主要途径之一,而导致人体感染的真正原因是器械或导管表面形成了菌膜.目的:对菌膜的形成机制,影响菌膜形成和发展的因素以及当前抑制菌膜形成的常用方法进行综述.方法:以"菌膜,生物膜,生物被膜","高分子,塑料,橡胶"和"biofilm,polymer,plastics,rubber"为检索词在medline、life sciences、Toxline plus、Derwent drug file、CBMDisc、CMCC等数据库和www.ncbi.nlm.nih.gov、www.uspto.gov、www.patent.com.cn等网站进行检索,得到相关国内外文献214篇.排除陈旧和内容类似文献,选择43篇文献进行综述.结果与结论:目前对菌膜在高分子器械表面形成过程和形成机制已经基本阐述清晰,但迄今为止,菌膜的研究多集中从微生物学、医学、基因角度进行,对菌膜的防治也是直接从利用抗生素的抑制方面考虑,文章着重从材料角度探讨抑制菌膜的可能途径及其在临床应用的可能性.     

聚乙烯表面的菌膜抑制及其表征

背景:研究表明造成高分子导管相关感染的原因是介入材料在体内停留一段时间容易引起病原菌在其表面吸附、定殖甚至形成菌膜,成为潜在的感染源.抑制菌膜的形成可显著改善高分子导管相关型感染的发生.目的:观察抗感染聚乙烯材料的抗菌效果及其对表面菌膜形成的抑制作用.设计、时间及地点:单一样本观察,于2008-06/2009-05在中科院理化所工程塑料国家工程研究中心完成,其中抗菌检测于2009-03在解放军总参谋部总医院完成.材料:有机抗菌剂为2,4,4'-三氯-2'-羟基二苯醚;无机抗菌剂为IONPURE~(R)系抗菌剂;低密聚乙烯.方法:低密度聚乙烯与有机和无机两种抗菌剂混合后先挤出造粒,然后注塑成片.主要观察指标:①用活菌平板计数法测定材料的抗菌性能.②平板超声波法及扫描电镜判断材料表面菌膜的形成情况.结果:①两种改性抗菌材料对大肠杆菌和金黄色葡萄球菌都有良好的抗菌效果,抗菌率达到99.9%.②细菌菌膜(菌膜)的形成主要包括黏附、繁殖和成熟3个阶段,添加有机抗菌剂的试样在菌膜形成前就可以显著抑制细菌在其表面生长,从而抑制菌膜形成,扫描电镜结果表明其表面未见菌膜形成.空白试样和无机抗菌试样表面均有大量细菌和细胞外基质黏附.结论:有机抗菌聚乙烯对大肠杆菌和金黄色葡萄球菌有良好的抑菌作用,可抑制细菌在材料表面形成菌膜,为防治医用导管相关感染提供了新的途径.     

高分子载体材料在脑胶质瘤治疗中的应用

目前对脑胶质瘤治疗的治疗效果并不理想,新的治疗手段正逐步应用于胶质瘤的治疗中.高分子载体材料是随着材料学、药物学研究和临床医学的发展而新兴的治疗技术.高分子材料优良的生物相容性、生物可降解性、降解速率的可调节性以及良好的可加工性能都为胶质瘤的治疗提供了新的治疗载体.高分子材料和所载药物分子的结构关系,提高载药效率,以及药物载体材料的结构、性能方面,不仅要考虑高分子材料的生物适应性,而且考虑它在体内的分布情况和生物降解性能、降解产物对机体的影响等问题.抗胶质瘤药物高分子载体的研究重点目前在于寻找选择性更强、疗效更好的载药材料.     

医用聚乳酸类高分子材料的应用

目的:阐述医用聚乳酸类高分子材料的需求,综述聚乳酸类高分子材料在生物医学领域的应用,并对其在医学领域的应用前景进行展望。资料来源:应用计算机检索ACS美国化学学会数据库2000-01/2006-12关于医用聚乳酸类高分子材料的文章,检索词“polylactide”;利用Elsevier Science全文电子期刊数据库2000-01/2006-12进行检索,检索词“polylactide”和全文检索“Medical polymeric material”。同时利用计算机检索中国期刊全文数据库1994-01/2005-12的相关文章,限定文章语言种类为中文,检索词“聚乳酸类医用高分子材料”。资料选择:对资料进行初审,纳入标准:①关于聚乳酸类医用高分子材料的需求。②医用聚乳酸类高分子材料的合成及应用。排除标准:重复性研究。资料提炼:共收集到符合上述要求的文献100篇,排除70篇重复性研究。30篇符合纳入标准:其中6篇关于聚乳酸类医用高分子材料的需求,24篇关于医用聚乳酸类高分子材料的合成及应用。资料综合:聚乳酸是一种具有良好的生物相容性和可生物降解的聚合物,最终的降解产物是二氧化碳和水,对人体无毒、无刺激。目前,聚乳酸类材料产品在医学领域广泛用于药物控制释放载体、组织工程、骨内固定、修复、手术缝合线、人造皮肤以及三维多孔支架等。结论:医用聚乳酸类高分子材料有非常广阔的应用前景,今后研究的重点是研发高效低成本的聚乳酸制备方法,合成适应于不同医疗或其他用途的、具有优良生物相容性的聚乳酸共聚物高分子材料。     

高分子材料在血液储存袋中的应用

聚氯乙烯（PVC）医用材料在血液保存方面具有极其重要的地位。然而，由于血液成分储存条件的不同，传统的PVC塑料已经不能满足各种血液成分保存的需要。大量的研究开始寻找传统的PVC血袋的替代材料，主要包括原有PVC材料的改进和非PVC材料的开发两个方面。本文就近年来高分子材料在血液保存袋中的应用进展作一综述。     

菌膜法快速药敏与鉴定

在日常工作中,往往得到的不足纯菌,尤其是痰、咽标本因这些部位本身有大量正常菌群,致病菌常散在其中,不易得到比较纯菌量足够多可直接上机鉴定的细菌,菌量不够就不能配制上机所需浓度的菌液。快速法鉴定与药敏试验能否成功,关键是备用菌液中细菌浓度准确与否。此步骤非常重要,它将影响药敏试验结果的精确度和正确性^[1]。     

高分子材料在鞍鼻整形术中的临床应用

应用三种不同的高分子材料:液态硅胶、硅橡胶鼻模?基磷灰石,设计了三种不同的鞍鼻整形术。对三种高分子材料的理化性质,生物特性??鞍鼻整形的手术方法作了详细的介绍和比较,提出了鼻整形并发症的预防和处理。     

医用高分子载体材料在抗肿瘤药物中的应用与作用

药物高分子载体是随着药物学研究、生物材料科学和临床医学的发展而新兴的给药技术。高分子材料的优良的生物相容性、生物可降解性、降解速率的可调节性以及良好的可加工性能,都为药物制剂的创新提供了便利和可能。高分子材料载体的合成,高分子材料和所载药物分子的结构关系,提高载药效率,以及药物载体材料的结构、在性能方面,不仅要考虑高分子材料的生物适应性,而且考虑它在体内的分布情况和生物降解性能、降解产物对机体的影响等问题都需要深入研究。抗肿瘤药物高分子载体的研究重点目前在于寻找选择性更强、疗效更好的载药材料。     

现代高分子材料在假肢矫形技术领域中的应用

材料学是现代科学技术发展的基础与支柱之一 ,大量新技术、新工艺的发展都得益于新型材料的发明。高分子材料是近年来迅速崛起和发展的一大类化工材料 ,在工农业生产、国防、日用生活品以及国民经济的各个领域都有重要的应用。假肢矫形技术的发展与进步同样离不开新型材料 ,特别是现代高分子材料在该领域的开发和应用。过去的 2 0年里 ,假肢矫形器的制作工艺发生了明显的变化 ,传统的材料如木材、金属、皮革以及天然纤维织物等 ,越来越广泛地被现代高分子材料所取代。这主要表现在热塑性塑料板材、树脂基复合材料、低温热塑材料等的应用。利…     

体内可分解性高分子材料的研究

本文以六酸亚锡为引发剂，十二烷醇为调节剂，进行丙交酯、乙交酯共聚。讨论了反应温度、反应时间、引发剂浓度、分子量调节剂、单体配比等反应条件对聚合转化率、分子量及其分布的影响。实验结果表明：引发剂含量０．０７５％、反应温度１７０℃、反应时间６ｈｒ为最佳反应条件，这时分子量、转化率都很高。     

Biofilm Formation and Effect of Caspofungin on Biofilm Structure of Candida Species Bloodstream Isolates

Candida biofilms are microbial communities, embedded in a polymeric matrix, growing attached to a surface, and are highly recalcitrant to antimicrobial therapy. These biofilms exhibit enhanced resistance against most antifungal agents except echinocandins and lipid formulations of amphotericin B. In this study, biofilm formation by different Candida species, particularly Candida albicans, C. tropicalis, and C. parapsilosis, was evaluated, and the effect of caspofungin (CAS) was assessed using a clinically relevant in vitro model system. CAS displayed in vitro activity against C. albicans and C. tropicalis cells within biofilms. Biofilm formation was evaluated after 48 h of antifungal drug exposure, and the effects of CAS on preformed Candida species biofilms were visualized using scanning electron microscopy (SEM). Several species-specific differences in the cellular morphologies associated with biofilms were observed. Our results confirmed the presence of paradoxical growth (PG) in C. albicans and C. tropicalis biofilms in the presence of high CAS concentrations. These findings were also confirmed by SEM analysis and were associated with the metabolic activity obtained by biofilm susceptibility testing. Importantly, these results suggest that the presence of atypical, enlarged, conical cells could be associated with PG and with tolerant cells in Candida species biofilm populations. The clinical implications of these findings are still unknown.Candida species are opportunistic pathogens that cause superficial and systemic diseases in critically ill patients (8, 22, 44) and are associated with high mortality rates (35%) and costly treatments (8, 19). They rank among the four most common causes of bloodstream infection in U.S. hospitals, surpassing gram-negative rods in incidence (6, 17).Recent studies suggest that the majority of disease produced by this pathogen is associated with a biofilm growth style (7, 16, 28, 48). Biofilms are self-organized communities of microorganisms that grow on an abiotic or biotic surface, are embedded in a self-produced matrix consisting of an extracellular polymeric substance (14, 15, 55), and when associated with implanted medical devices are commonly refractive to antimicrobial therapy.As opportunistic pathogens, Candida species are able to attach to polymeric surfaces and generate a biofilm structure, protecting the organisms from the host defenses and antifungal drugs (11, 16, 45, 48). Candida biofilms are more resistant than their planktonic counterparts to various antifungal agents, including amphotericin B (AMB), fluconazole, itraconazole, and ketoconazole (20, 38, 50). However, the molecular basis for the antifungal resistance of biofilm-related organisms is not completely understood.The complex architecture of Candida biofilms observed both in vitro and in vivo suggests that morphological differentiation to produce hyphae plays an important role in biofilm formation and maturation (7, 32, 33). Baillie and Douglas demonstrated that although mutant cells fixed in either a hyphal or a yeast form can develop into biofilms, the hyphal structure is the essential element for providing the integrity and multilayered architecture of a biofilm (4). It has been reported that Candida parapsilosis, C. glabrata, and C. tropicalis biofilms are not as large as those generated by C. albicans; however, further structural analysis studies are needed to describe biofilm formation by these organisms (30, 31).The mechanisms responsible for the resistance characteristics displayed by Candida biofilms are unclear. Possible mechanisms include a decreased growth rate; nutrient limitation of cells in the biofilm; expression of resistance genes, particularly those encoding efflux pumps; increased cell density; cell aging; or the presence of “persister” cells in the biofilm (1, 3, 5, 29, 34, 36, 38, 43, 46, 48, 50, 51).The echinocandins are a novel class of semisynthetic amphiphilic lipopeptides that display important antifungal activity. The echinocandins that are presently marketed are caspofungin (CAS), micafungin, and anidulafungin. The echinocandins show considerable efficacy in vitro and in vivo in the treatment of candidemia and invasive candidiasis (25, 27, 42). CAS is the first antifungal agent to be licensed that inhibits the synthesis of β-1,3-glucan, the major structural component of Candida cell walls; glucan synthesis might prove to be a particularly effective target for biofilms (29, 31, 38, 48, 50). The paradoxical attenuation of antifungal activity at high echinocandin concentrations is a phenomenon that usually occurs with C. albicans isolates and appears to be specific to CAS among echinocandins. The cells surviving at high concentrations appear to be subject to some drug effect, showing evidence of slowed growth in the presence of CAS (53, 54). Recent studies have described this effect in Candida species biofilms (24, 37, 47); however, we are not aware of studies that have elucidated the effect of CAS on Candida biofilm structure. The present study was designed to (i) characterize the in vitro biofilm growth of Candida species bloodstream isolates and (ii) use scanning electron microscopy (SEM) to obtain visual evidence of the effect of CAS on biofilm morphology changes associated with paradoxical growth (PG).     

中国生物被膜相关研究文献分析

目的分析1997～2007年我国生物被膜相关研究文献，为我国抗感染领域科研工作者确定研究课题、利用和探索文献提供参考与借鉴。方法检索《中国医院知识仓库》、《中文科技期刊数据库》收录的生物被膜研究文献，采用文献计量学方法，对纳入研究文献的年份分布、作者单位、基金资助、研究内容等进行统计分析，并评价纳入研究中的随机对照试验的质量。结果我国生物被膜研究总文献量为491篇，纳入符合标准文献240篇；高等院校是该领域的主导力量；我国生物被膜的研究菌种集中于铜绿假单胞菌、葡萄球菌，并且主要以体外模型为主；对生物被膜的防控仍较多关注于现有抗菌药物的利用。纳入的研究中仅有4篇RCT，且方法学质量均为c级。结论我国生物被膜研究能够紧跟国际步伐，但结合工程学、材料学、免疫学等各个学科领域研究的广度和深度还需加强。     

Effects of Bacteriocins on Methicillin-Resistant Staphylococcus aureus Biofilm

Control of biofilms formed by microbial pathogens is an important subject for medical researchers, since the development of biofilms on foreign-body surfaces often causes biofilm-associated infections in patients with indwelling medical devices. The present study examined the effects of different kinds of bacteriocins, which are ribosomally synthesized antimicrobial peptides produced by certain bacteria, on biofilms formed by a clinical isolate of methicillin-resistant Staphylococcus aureus (MRSA). The activities and modes of action of three bacteriocins with different structures (nisin A, lacticin Q, and nukacin ISK-1) were evaluated. Vancomycin, a glycopeptide antibiotic used in the treatment of MRSA infections, showed bactericidal activity against planktonic cells but not against biofilm cells. Among the tested bacteriocins, nisin A showed the highest bactericidal activity against both planktonic cells and biofilm cells. Lacticin Q also showed bactericidal activity against both planktonic cells and biofilm cells, but its activity against biofilm cells was significantly lower than that of nisin A. Nukacin ISK-1 showed bacteriostatic activity against planktonic cells and did not show bactericidal activity against biofilm cells. Mode-of-action studies indicated that pore formation leading to ATP efflux is important for the bactericidal activity against biofilm cells. Our results suggest that bacteriocins that form stable pores on biofilm cells are highly potent for the treatment of MRSA biofilm infections.     

甲壳素对大肠埃希菌生物被膜形成的作用

目的 探讨甲壳素对大肠埃希菌生物被膜形成的作用.方法 以空白导管(对照组)和包被甲壳素的导管(实验组)为裁体,构建7 d的大肠埃希菌生物被膜模型,然后对每组细菌计数、测定结晶紫染色后的吸光度值、扫描电镜(SEM)观察.结果 对照组和实验组的细菌计数值(×107 cfu/ml)是2.29和2.15;吸先度值是0.137和0.138.扫描电镜下,对照组的细菌分布较均匀、密集;实验组的细菌分布不均匀、密集.结论 甲壳素对形成7 d的大肠埃希茼生物被膜不具有抑制作用.     

Effects of Iron Chelators on the Formation and Development of Aspergillus fumigatus Biofilm

Iron acquisition is crucial for the growth of Aspergillus fumigatus. A. fumigatus biofilm formation occurs in vitro and in vivo and is associated with physiological changes. In this study, we assessed the effects of Fe chelators on biofilm formation and development. Deferiprone (DFP), deferasirox (DFS), and deferoxamine (DFM) were tested for MIC against a reference isolate via a broth macrodilution method. The metabolic effects (assessed by XTT [2,3-bis[2-methoxy-4-nitro-5-sulfophenyl]-2H-tetrazolium-5-carboxanilide inner salt]) on biofilm formation by conidia were studied upon exposure to DFP, DFM, DFP plus FeCl₃, or FeCl₃ alone. A preformed biofilm was exposed to DFP with or without FeCl₃. The DFP and DFS MIC₅₀ against planktonic A. fumigatus was 1,250 μM, and XTT gave the same result. DFM showed no planktonic inhibition at concentrations of ≤2,500 μM. By XTT testing, DFM concentrations of <1,250 μM had no effect, whereas 2,500 μM increased biofilms forming in A. fumigatus or preformed biofilms (P < 0.01). DFP at 156 to 2,500 μM inhibited biofilm formation (P < 0.01 to 0.001) in a dose-responsive manner. Biofilm formation with 625 μM DFP plus any concentration of FeCl₃ was lower than that in the controls (P < 0.05 to 0.001). FeCl₃ at ≥625 μM reversed the DFP inhibitory effect (P < 0.05 to 0.01), but the reversal was incomplete compared to the controls (P < 0.05 to 0.01). For preformed biofilms, DFP in the range of ≥625 to 1,250 μM was inhibitory compared to the controls (P < 0.01 to 0.001). FeCl₃ at ≥625 μM overcame inhibition by 625 μM DFP (P < 0.001). FeCl₃ alone at ≥156 μM stimulated biofilm formation (P < 0.05 to 0.001). Preformed A. fumigatus biofilm increased with 2,500 μM FeCl₃ only (P < 0.05). In a strain survey, various susceptibilities of biofilms of A. fumigatus clinical isolates to DFP were noted. In conclusion, iron stimulates biofilm formation and preformed biofilms. Chelators can inhibit or enhance biofilms. Chelation may be a potential therapy for A. fumigatus, but we show here that chelators must be chosen carefully. Individual isolate susceptibility assessments may be needed.     

Biofilm formation by Exiguobacterium sp. DR11 and DR14 alter polystyrene surface properties and initiate biodegradation

Polystyrene is a chemically inert synthetic aromatic polymer. This widely used form of plastic is recalcitrant to biodegradation. The exponential production and consumption of polystyrene in various sectors has presented a great environment risk and raised the problem of waste management. Biodegradation by bacteria has previously shown great potential against various xenobiotics but there are only a few reports concerning polyolefins. By screening wetland microbes, we found two bacterial species – Exiguobacterium sibiricum strain DR11 and Exiguobacterium undae strain DR14 which showed promising biodegradation potential against polystyrene. In this study, we report the degradation of non-irradiated solid polystyrene material after incubation with these isolates. Growth studies suggested that the Exiguobacterium strains utilize polystyrene as a carbon source. Moreover, our data suggest that polymer degradation was initiated by biofilm formation over the PS surface leading to alteration in the physical properties of the material. Surface property analysis by AFM revealed significantly enhanced roughness resulting in reduced surface hydrophobicity of polystyrene. Fourier-transfer infrared (FT-IR) spectroscopic analysis showed breakdown of polystyrene backbone by oxidation. The extent of deterioration was further determined by percent weight reduction of polystyrene after incubation with bacteria. Our data support the fact that strains of extremophile bacterium Exiguobacterium are capable of degrading polystyrene and can be further used to mitigate the environmental pollution caused by plastics.

Isolation and characterization Exiguobacterium sp. DR11 and DR14 from wetlands able to establish biofilm and alter polystyrene surface properties.     

克拉霉素对细菌生物被膜作用的研究进展

细菌生物被膜，又称菌膜(bacterial biofilm)是单一或多种细菌在不利于其生长的环境下，产生藻酸盐多糖使细菌相互黏连形成膜状物附于病灶的表面或导管内。这是细菌为适应环境维持自身生命所发生的形态学的变化，从而增强了细菌对外环境的抵抗力。这也成为一些细菌对抗生素产生广泛耐药的重要原因。临床上许多顽固性，难治性感染可能均与形成细菌生物被膜有关。