biosafety

生物安全
  • 文章类型: Journal Article
    近年来,将锌(Zn)合金用作可降解金属材料在生物医学骨植入材料领域引起了相当大的关注。本研究通过三维(3D)打印技术研究了使用Zn-1Mg-0.1Sr合金制造多孔支架,选择性激光熔化(SLM)。结果表明,多孔Zn-1Mg-0.1Sr合金支架具有微孔结构,抗压强度为33.71±2.51MPa,屈服强度(YS)为27.88±1.58MPa,弹性模量(E)为2.3±0.8GPa。在浸泡实验中,浸渍溶液的Zn2+浓度为2.14±0.82mg/L,Sr2+浓度为0.34±0.14mg/L,平均pH为7.61±0.09。多孔Zn-1Mg-0.1Sr合金在14天内表现出12.82±0.55%的重量损失和0.36±0.01mm/年的腐蚀降解速率。细胞计数试剂盒-8(CCK-8)测定用于检查细胞的活力。结果表明,10%和20%提取物显着提高成骨细胞前体细胞(MC3T3-E1)的活性,细胞毒性等级为0,表明安全性和无毒性。总之,多孔Zn-1Mg-0.1Sr合金支架表现出优异的力学性能,适当的降解率,和良好的生物安全性,使其成为可降解金属骨植入物的理想候选者。
    In recent years, the use of zinc (Zn) alloys as degradable metal materials has attracted considerable attention in the field of biomedical bone implant materials. This study investigates the fabrication of porous scaffolds using a Zn-1Mg-0.1Sr alloy through a three-dimensional (3D) printing technique, selective laser melting (SLM). The results showed that the porous Zn-1Mg-0.1Sr alloy scaffold featured a microporous structure and exhibited a compressive strength (CS) of 33.71 ± 2.51 MPa, a yield strength (YS) of 27.88 ± 1.58 MPa, and an elastic modulus (E) of 2.3 ± 0.8 GPa. During the immersion experiments, the immersion solution showed a concentration of 2.14 ± 0.82 mg/L for Zn2+ and 0.34 ± 0.14 mg/L for Sr2+, with an average pH of 7.61 ± 0.09. The porous Zn-1Mg-0.1Sr alloy demonstrated a weight loss of 12.82 ± 0.55% and a corrosion degradation rate of 0.36 ± 0.01 mm/year in 14 days. The Cell Counting Kit-8 (CCK-8) assay was used to check the viability of the cells. The results showed that the 10% and 20% extracts significantly increased the activity of osteoblast precursor cells (MC3T3-E1), with a cytotoxicity grade of 0, which indicates safety and non-toxicity. In summary, the porous Zn-1Mg-0.1Sr alloy scaffold exhibits outstanding mechanical properties, an appropriate degradation rate, and favorable biosafety, making it an ideal candidate for degradable metal bone implants.
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  • 文章类型: Journal Article
    在COVID-19大流行期间,急救人员面临重大的生物安全挑战,尤其是在处理病人运输时,有可能让他们感染.PANDEM-2(欧洲大流行准备和应对项目)项目,由地平线2020计划资助,试图调查整个欧盟紧急医疗系统面临的挑战。葡萄牙国家紧急医疗研究所(INEM)的急救人员被认为是欧洲成员国国家急救机构的代表性运作模式,因为他们在COVID-19大流行期间发挥了关键作用。因此,他们被要求完成一项关于他们与COVID-19大流行相关专业活动的在线调查。调查的重点是他们对当前生物安全准则及其操作实践的看法。它涵盖了对现有协议的意见,患者运输过程中的技术问题,以及患者到达医院后的问题。关键发现揭示了对风险评估的担忧,准则的不足,以及设备接入方面的差距。这项调查强调了发展精简的重要性,适应性生物安全协议,更好地协调院前和院内服务,以及可扩展的发展,具有成本效益的生物安全解决方案。根据我们的发现,我们建议改进国家和欧洲生物安全指令,并倡导在大流行期间简化适应。
    During the COVID-19 pandemic, first responders faced significant biosafety challenges, especially while handling patient transport, potentially exposing them to infection. The PANDEM-2 (European project on pandemic preparedness and response) project, funded by the Horizon 2020 program, sought to investigate the challenges confronting Emergency Medical Systems throughout the EU. First responders from Portugal\'s National Institute of Medical Emergency (INEM) were considered as a representative operational model of the national first responder agencies of European member states because they played a critical role during the COVID-19 pandemic. As a result, they were asked to complete an online survey about their COVID-19 pandemic-related professional activities. The survey focused on their perspectives on current biosafety guidelines and their operational practices. It covered opinions on existing protocols, technical concerns during patient transport, and issues after the patients arrived at the hospital. The key findings revealed concerns about risk assessment, the inadequacy of guidelines, and disparities in equipment access. This survey emphasizes the importance of developing streamlined, adaptable biosafety protocols, better coordination between prehospital and in-hospital services, and the development of scalable, cost-effective biosafety solutions. Based on our findings, we propose improvements to national and European biosafety directives and advocate for streamlined adaptation during pandemics.
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  • 文章类型: Journal Article
    由于化疗药物对肺癌的严重副作用,以及磁场的抗肿瘤特性和高安全性,本研究将中等或超高强度静力学磁场(SMFs)与桔梗皂苷D(PD)相结合,以探讨抗肿瘤效率和生物安全性。比较了有或没有中度和超高SMF的PD对携带A549细胞的小鼠的抗肿瘤作用。老鼠体重,食物/水的摄入量,血液学常规,血液生物化学,检查肿瘤重量和组织苏木精和伊红(H&E)染色。使用高架迷宫测量行为,开放领域和生命体征测试。使用RNA测序(RNA-seq)检测PD和SMF的组合靶标。结果表明,与2mg/kgPD组相比,22特斯拉(T)SMF组的抗肿瘤作用提高了3.6倍(肿瘤生长抑制作用=10.08%),而150mTSMF的抗肿瘤作用仅比PD高1.56倍。虽然PD减少了食物的摄入量,体重没有显着差异,PD和SMF组的水摄入量或食物消耗。行为结果表明,PD改善了小鼠的烦躁不安,但SMFs减少了这种影响。然而,血常规无明显异常,血液生化检查,H&E染色或器官指数,除了有或没有SMFs的PD降低了肾脏指数。RNA测序(RNA-seq)表明SMFs和PD协同靶向表达与肿瘤生长相关的基因,炎症和神经系统疾病。本研究显示了中度或超高SMF联合PD的抗肿瘤疗效和生物安全性。在肺癌的治疗中只有很少的副作用,从而支持磁场临床应用的进一步研究。
    Due to the serious side effects of chemotherapy drugs against lung cancer, and the antitumor properties and high safety of magnetic fields, the present study combined moderate or ultra-high intensity statics magnetic fields (SMFs) with platycodin D (PD) to explore the antitumor efficiency and biosafety. The antitumor effects of PD with or without moderate and ultra-high SMFs on A549 cells bearing mice were compared. Mouse body weight, food/water intake, hematology routine, blood biochemistry, tumor weight and tissues hematoxylin and eosin (H&E) staining were examined. Behavior was measured using the elevated plus maze, open field and vital signs tests. The combined targets of PD and SMFs were detected using RNA-sequencing (RNA-seq). The results showed that the antitumor effect of 22 Tesla (T) SMF group was 3.6-fold higher compared with that of the 2 mg/kg PD group (tumor growth inhibition=10.08%), while the antitumor effect of 150 mT SMF was only 1.56-fold higher compared with that of PD. Although PD reduced the food intake, there was no significant difference in body weight, water intake or food consumption among PD and SMF groups. Behavioral results indicated that PD ameliorated dysphoria in mice, but SMFs reduced this effect. However, no significant abnormalities were found in routine blood, blood biochemistry test, H&E staining or organ index, except renal index which was reduced by PD with or without SMFs. RNA-sequencing (RNA-seq) demonstrated that SMFs and PD synergistically targeted the expression of genes associated with tumor growth, inflammation and neurological disease. The present study showed the antitumor efficacy and biosafety of moderate or ultra-high SMF combined with PD, which exhibited only few side effects in the treatment of lung cancer, thus supporting further research for the clinical application of magnetic fields.
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  • 文章类型: Journal Article
    基因治疗的生物安全性仍然是直接和细胞介导递送编码生物活性分子的重组cDNA以进行先天性或获得性疾病的致病性矫正的关键问题。用于递送治疗基因的载体系统和细胞载体的多样性揭示了在实际医学中开发和实施安全有效的含有人工遗传物质的药物用于治疗人类疾病的困难。因此,在这项研究中,我们评估了使用携带编码人血管内皮生长因子(VEGF165)或报告绿色荧光蛋白(GFP)的cDNA的腺病毒载体(Ad5)基因修饰的脐带血单个核细胞(UCB-MCs)的转录组和分泌组的变化。用Ad5-VEGF165和MOI为10的Ad5-GFP转导的UCB-MC的初步分析显示在mRNA和蛋白质水平上基因修饰的UCB-MC中有效的转基因表达。天然UCB-MC的全转录组测序,UCB-MC+Ad5-VEGF165和UCB-MC+Ad5-GFP表现出个体样品的变异性,而不是Ad5或重组vegf165表达对UCB-MC转录组的影响。多重分泌组分析表明,用Ad5-GFP和Ad5-VEGF165转导UCB-MCs均不影响所研究细胞因子的分泌,趋化因子,和生长因子通过基因修饰的细胞。这里,我们表明,用携带编码人VEGF165的cDNA的Ad5转导的UCB-MC有效表达转基因并保留转录组和分泌组模式。该数据证明了使用UCB-MC作为治疗基因的细胞载体的生物安全性。
    The biosafety of gene therapy remains a crucial issue for both the direct and cell-mediated delivery of recombinant cDNA encoding biologically active molecules for the pathogenetic correction of congenital or acquired disorders. The diversity of vector systems and cell carriers for the delivery of therapeutic genes revealed the difficulty of developing and implementing a safe and effective drug containing artificial genetic material for the treatment of human diseases in practical medicine. Therefore, in this study we assessed changes in the transcriptome and secretome of umbilical cord blood mononuclear cells (UCB-MCs) genetically modified using adenoviral vector (Ad5) carrying cDNA encoding human vascular endothelial growth factor (VEGF165) or reporter green fluorescent protein (GFP). A preliminary analysis of UCB-MCs transduced with Ad5-VEGF165 and Ad5-GFP with MOI of 10 showed efficient transgene expression in gene-modified UCB-MCs at mRNA and protein levels. The whole transcriptome sequencing of native UCB-MCs, UCB-MC+Ad5-VEGF165, and UCB-MC+Ad5-GFP demonstrated individual sample variability rather than the effect of Ad5 or the expression of recombinant vegf165 on UCB-MC transcriptomes. A multiplex secretome analysis indicated that neither the transduction of UCB-MCs with Ad5-GFP nor with Ad5-VEGF165 affects the secretion of the studied cytokines, chemokines, and growth factors by gene-modified cells. Here, we show that UCB-MCs transduced with Ad5 carrying cDNA encoding human VEGF165 efficiently express transgenes and preserve transcriptome and secretome patterns. This data demonstrates the biosafety of using UCB-MCs as cell carriers of therapeutic genes.
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  • 文章类型: Journal Article
    该研究旨在通过合成新型银纳米复合材料来增强凹坑和裂缝密封剂的防龋性能,并评价其体内外力学性能和生物安全性。
    通过细菌抑制区检测合成蛋壳/Ag的抗菌性能,最低抑菌浓度,荧光染色和扫描电镜。然后将合成产品与凹坑和裂缝密封剂混合以制备样品,以及它们对机械性能的影响,抗菌性能和细胞毒性进行了评价。此外,根据ISO10933标准建立金黄地鼠口腔黏膜接触模型,以评估局部刺激和全身效应。
    新型纳米复合蛋壳/Ag被证实具有很强的广谱抗菌活性,蛋壳/Ag修饰的窝沟封闭剂对常见龋齿细菌生物膜具有很强的抗菌性能,机械性能没有任何显著变化。梯度稀释提取物显示出可接受的细胞毒性,在金色仓鼠口腔接触模型中,局部粘膜组织无明显异常,血液指数,或肝脏和肾脏组织病理学。
    这些发现表明,蛋壳/Ag结合窝沟封闭剂在体外和体内具有很强的抗菌活性和优异的生物安全性,使其成为临床应用的有希望的候选者。
    UNASSIGNED: The study aims to enhance the anti-caries performance of pit and fissure sealants through the synthesis of novel silver nanocomposites, and to evaluate their mechanical properties and biological safety in vitro and in vivo.
    UNASSIGNED: The antibacterial properties of synthetic eggshell/Ag were detected by bacterial inhibition zone, minimum bacteriostatic concentration, fluorescence staining and scanning electron microscopy. The synthetic products were then combined with pit and fissure sealants to prepare specimens, and their effects on mechanical properties, antibacterial properties and cytotoxicity were evaluated. Furthermore, an oral mucosal contact model of golden hamsters was established according to the ISO10933 standard to evaluate local stimulation and systemic effects.
    UNASSIGNED: The novel nanocomposite eggshell/Ag was confirmed to exhibit strong broad-spectrum antibacterial activity, and that the eggshell/Ag-modified pit and fissure sealant had strong antibacterial properties against common dental caries bacterial biofilms, without any significant change in mechanical properties. The gradient dilution extract showed acceptable cytotoxicity, and in the golden hamster oral contact model, there were no visible abnormalities in local mucosal tissues, blood indices, or liver and kidney histopathology.
    UNASSIGNED: These findings suggest that eggshell/Ag combined with pit and fissure sealants has strong antibacterial activity and excellent biosafety in vitro and in vivo, making it a promising candidate for clinical applications.
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  • 文章类型: Journal Article
    背景:这项研究的目的是分析公立大学医院护理专业人员对标准预防措施的遵守情况,并确定相关因素。
    方法:这是一项针对公立大学医院护理人员的横断面研究。参与者提供了社会人口统计学和免疫数据,关于标准预防措施和职业事故史的培训数据,并回复了关于遵守标准预防措施(QASP)的问卷。进行描述性数据分析和皮尔逊卡方检验(χ²),随后进行Fisher精确检验,以验证遵守标准预防措施(总分≥76分)与样本表征变量之间的关联.此外,二元逻辑回归显示了样本表征变量对标准预防措施依从性的比值比(OR).p值≤0.05被认为具有统计学意义。
    结果:遵守标准预防措施的平均得分,通过QASP,经护理专业人员评定为70.5分。未确定遵守标准预防措施与专业人员样品表征变量之间的关联。然而,观察到有经验的专业人员(在该机构工作≥15年)更有可能坚持标准预防措施(OR0.062;IC95%[0.006-0.663];p=0.021).
    结论:一般来说,在这项研究中,从事卫生服务工作的护理专业人员对标准预防措施的遵守可以被认为是不够的,突出手部卫生习惯的主要弱点,使用个人防护设备(PPE),收回用过的针头,以及在遭受职业事故后的行为。经验丰富的专业人员更有可能遵守标准预防措施。
    The aim of this study was to analyze the adherence to standard precautions by nursing professionals in a public university hospital, and to identify associated factors.
    This was a cross-sectional study with the nursing staff of a public university hospital. The participants provided sociodemographic and immunization data, training data on standard precautions and occupational accident history, and responded to the questionnaire on adherence to standard precautions (QASP). Descriptive data analysis and Pearson\'s Chi-square test (χ²) were performed, followed by Fisher\'s exact test to verify the association between the adherence to standard precautions (total score ≥ 76 points) and the sample characterization variables. Additionally, binary logistic regression indicated the odds ratio (OR) of the sample characterization variables for adherence to standard precautions. A p value ≤ 0.05 was considered statistically significant.
    The average score for adherence to standard precautions, through QASP, by nursing professionals evaluated was 70.5 points. Association between the adherence to standard precautions and the professionals\' sample characterization variables was not identified. However, it was observed that experienced professionals (≥15 years of experience in the institution) were more likely to adhere to standard precautions (OR 0.062; IC95% [0.006-0.663]; p = 0.021).
    In general, the adherence to standard precautions by nursing professionals working in health service in this study can be considered inadequate, highlighting major weaknesses in hand hygiene practices, use of personal protective equipment (PPE), recapping of used needles, and conduct after suffering occupational accidents. Experienced professionals were more likely to adhere to standard precautions.
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  • 文章类型: Journal Article
    为评价转基因玉米的生态风险提供更多的依据。两种转基因玉米(DBN9868,表达PAT和EPSPS基因,和DBN9936,表达Cry1Ab和EPSPS基因)通过直接观察和诱捕三年进行了研究。记录的节肢动物物种属于19目87科,包括Aphidoidea,菊科,球藻科,菊科和Araneae。物种丰富,Shannon-Wiener多样性指数,Pielou均匀度指数,对玉米田节肢动物群落优势度指数和群落相似性指数进行统计分析,结果表明:(1)转基因玉米和非转基因玉米节肢动物群落的生物多样性差异小于不同常规品种之间的差异;(2)地栖节肢动物群落之间的差异小于植物性节肢动物群落之间的差异;(3)鳞翅目,Bt玉米的目标害虫,不是玉米田的主要人口,玉米田中主要的节肢动物种群在几年和几个月之间变化很大。结合这些结果,我们得出结论,转基因玉米DBN9868和DBN9936对田间节肢动物群落没有显着影响。
    In order to provide more evidence for the evaluation of the ecological risks of transgenic maize, arthropod population dynamics and biodiversity in fields planted with two kinds of transgenic maize (DBN9868, expressing the PAT and EPSPS genes, and DBN9936, expressing the Cry1Ab and EPSPS gene) were investigated by direct observation and trapping for three years. The recorded arthropod species belonged to 19 orders and 87 families, including Aphidoidea, Chrysomelidae, Coccinellidae, Chrysopidae and Araneae. The species richness, Shannon-Wiener diversity index, Pielou evenness index, dominance index and community similarity index of arthropod communities in maize fields were statistically analyzed, and the results showed that (1) the biodiversity difference of arthropod communities between transgenic maize and non-transgenic maize was smaller than that between different conventional cultivars; (2) the differences between ground-dwelling arthropod communities were less obvious than those between plant-inhabiting arthropod communities; and (3) Lepidoptera, the target pests of Bt maize, were not the dominant population in maize fields, and the dominant arthropod population in maize fields varied greatly between years and months. Combining those results, we concluded that the transgenic maize DBN9868 and DBN9936 had no significant effect on the arthropod communities in the field.
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  • 文章类型: Journal Article
    未经评估:医疗保健组织是复杂的系统,其中医疗保健专业人员,病人,生物材料,和设备不断互动,并提供反馈,结果非常重要。这些是复杂自适应系统的特征。医疗保健的提供需要协调,但必须依赖于基本功能的委派。因此,必须有一支敬业的员工队伍来确保患者的最佳结果。因此,人的表现因素在确保优质医疗保健服务的存在和不存在必须避免的结果方面发挥着关键作用。\"
    UNASSIGNED:管理层的承诺是实施高可靠性组织(HRO)原则的前提。一个来自中层管理人员的团队参与进来,并提供了适当的管理工具,优先化,评估,并在其操作系统中应用安全问题的解决方案。
    UNASSIGNED:本文记录了美国国立卫生研究院(NIH)为适应伊斯兰堡校园内的诊断实验室和疫苗生产设施而做出的努力,巴基斯坦,并试图吸取一些教训,以了解如何在其他地方的此类设施中有效地复制这种方法。
    UNASSIGNED:像NIH这样的公共卫生机构提供重要的产品和服务,这些产品和服务本身就具有生产风险,失败的后果可能是灾难性的。采用HRO原则不仅是提高安全性的一种方法,以及任何环境下的整体组织绩效,包括低资源设置,并可以作为其他机构的可实施过程。
    UNASSIGNED: Healthcare organizations are complex systems where healthcare professionals, patients, biological materials, and equipment constantly interact and provide feedback with highly consequential outcomes. These are the characteristics of a complex adaptive system. Healthcare delivery requires coordination but it necessarily relies on delegation of essential functions. It is thus essential to have an engaged workforce to ensure optimal outcomes for patients. Thus human performance factors play a key role in ensuring both the presence of excellent healthcare provision and the absence of outcomes that must be avoided-\"never events.\"
    UNASSIGNED: The commitment of management was a precondition for the implementation of the high-reliability organization (HRO) principles. A team from middle management was engaged and provided with appropriate management tools for identifying, prioritizing, assessing, and applying solutions for the safety concern in their operating systems.
    UNASSIGNED: This article documents efforts at the National Institute of Health (NIH) to adapt the principles of HROs to diagnostic laboratories and vaccine production facilities at its campus in Islamabad, Pakistan, and seeks to draw some lessons for how this approach can be usefully replicated in such facilities elsewhere.
    UNASSIGNED: Public health institutes such as NIH deliver vital products and services that are inherently risky to produce, where the consequence of failure can be catastrophic. Adopting the HRO principles is an approach to improving not just safety, but also the overall organizational performance in any setting, including low-resource settings, and can serve as an implementable process for other institutions.
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  • 文章类型: Journal Article
    随着高度传播的Omicron变体(BA4和BA.5)的到来,牙科面临另一个季节性挑战,以保持牙科护理和教育的生物安全性。为了保护病人,学生,教师和医疗保健专业人员,本文介绍了用于日常牙科护理和教育的可持续生物安全环境。牙科临床医生开发的设置,流行病学家,牙科教师由现代技术的组合组成,专注于病毒途径的空气传播部分。在实际临床环境中应用18个月后,已对引入的生物安全性设置进行了临床评估。该协议具有三个基本支柱:(1)UVC空气消毒;(2)具有雾化扩散器的经过认证的杀病毒本质的空气饱和度;(3)补充解决方案,包括远程医疗和3D打印。采用假名在线智能表单作为评价方法。该协议的前提是每个人都是假设的渐近载体。对115例患者反馈的临床评估结果表明,使用该协议未观察到或报告患者之间或医生与护士之间的病毒传播,反之亦然,尽管有9名患者回顾性地承认,门诊就诊可能具有传染性。尽管这些有希望的结果,需要更大的临床样本和对当前突变菌株的说明,才能得出关于当前牙科环境中方案杀病毒效率的可靠结论。
    With the arrival of the highly transmissible Omicron variants (BA.4 and BA.5), dentistry faces another seasonal challenge to preserve the biosafety of dental care and education. With the aim of protecting patients, students, teachers and healthcare professionals, this paper introduces a prospective sustainable biosafety setting for everyday dental care and education. The setting developed by dental clinicians, epidemiologists, and teachers of dentistry consists of a combination of modern technologies focused on the air-borne part of the viral pathway. The introduced biosafety setting has been clinically evaluated after 18 months of application in the real clinical environment. The protocol has three fundamental pillars: (1) UVC air disinfection; (2) air saturation with certified virucidal essences with nebulizing diffusers; (3) complementary solutions including telehealth and 3D printing. A pseudonymous online smart form was used as the evaluation method. The protocol operates on the premise that everybody is a hypothetical asymptomatic carrier. The results of a clinical evaluation of 115 patient feedbacks imply that no virus transmission from patient to patient or from doctor to nurse was observed or reported using this protocol, and vice versa, although nine patients retrospectively admitted that the clinic visit is likely to be infectious. Despite these promising results, a larger clinical sample and exposition to the current mutated strains are needed for reliable conclusions about protocol virucidal efficiency in current dental environments.
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  • 文章类型: Journal Article
    先前已经报道,石墨烯氧化物/铜纳米衍生物(GO/Cu)-并入的壳聚糖/透明质酸支架可能是用于管理感染的伤口愈合的有前途的伤口敷料。本研究的目的是深入探索潜在的抗菌机制和协同成骨活性,以及GO/Cu纳米复合材料的体内抗感染行为,使他们成为建立植入式生物材料修复感染骨缺损的可能候选人。通过对膜完整性的检测,探讨了纳米复合材料的抗菌机理,氧化应激,和代谢酶活性。然后,证实了与骨髓间充质干细胞(rBMSCs)的细胞相容性和成骨潜能,并建立大鼠皮下细菌感染模型,验证纳米复合材料的体内抗感染性能和生物安全性。发现三磷酸腺苷的泄漏,蛋白质,减少细菌细胞中的糖,指示细菌膜的渗透性受损,并促进响应氧化应激的活性氧和无序代谢酶活性的产生是GO/Cu纳米复合材料协同抗菌作用的可能分子机制。此外,在GO/Cu纳米复合材料(质量比=2:1)中发现与rBMSCs具有良好的细胞相容性并促进成骨分化,这也表现出令人满意的体内抗感染性能,减少炎症,和可接受的生物安全性。根据我们的结果,受损的细菌膜,增加ROS产量,关键酶代谢紊乱是GO/Cu纳米复合材料引起的细菌杀伤事件的主要抗菌机制,还显示出增强的成骨活性,体内抗感染能力,和可接受的细胞相容性和生物安全性。因此,GO/Cu(2:1)纳米复合材料是改善当前用于对抗细菌污染的骨缺损的骨替代物的生物学性能的潜在策略。
    It has been previously reported that graphene oxide/copper nanoderivative (GO/Cu)-incorporated chitosan/hyaluronic acid scaffolds might be promising wound dressings for the management of infected wound healing. The aim of the present research is to deeply explore the potential antimicrobial mechanisms and synergistic osteogenic activity, as well as the in vivo anti-infective behavior of GO/Cu nanocomposites, making them possible candidates for establishing implantable biomaterials for the repair of infected bone defects. The antibacterial mechanisms of the nanocomposites were explored through the examination of membrane integrity, oxidative stress, and metabolic enzyme activities. Then, the cytocompatibility with bone mesenchymal stem cells (rBMSCs) and osteogenic potential were confirmed, and a subcutaneous bacterial infection model in rats was also established to verify the in vivo anti-infective property and biosafety of the nanocomposites. It was found that leakage of adenosine triphosphate, proteins, and reducing sugars from the bacterial cells, indicative of damaged permeability of bacterial membranes, and promoted production of reactive oxygen species and disordered metabolic enzyme activities in response to oxidative stress were possible molecular mechanisms responsible for the synergistic antibacterial effects of the GO/Cu nanocomposites. Additionally, good cytocompatibility with rBMSCs and promoted osteogenic differentiation were found in GO/Cu nanocomposites (mass ratio = 2:1), which also demonstrated satisfactory in vivo anti-infective performance, reduced inflammation, and acceptable biosafety. Based on our results, damaged bacterial membranes, increased ROS production, and disorders of crucial enzyme metabolism were the main antibacterial mechanisms involved in the bacterium-killing events caused by the GO/Cu nanocomposites, which also showed enhanced osteogenic activity, in vivo anti-infective capability, and acceptable cytocompatibility and biosafety. Therefore, GO/Cu (2:1) nanocomposites are a potential strategy for improving the biological performance of current bone substitutes used for combating bacterial-contaminated bone defects.
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