In vitro model

体外模型
  • 文章类型: Journal Article
    在过去的几十年里,生物膜研究呈指数级增长,可以说是由于它们在导管和植入物等异物表面上形成时对医院获得性感染的贡献。然而,将在实验室中获得的知识转化到临床的速度很慢,并且/或者研究团队通常不会尝试将定义为“长凳到床边”的话题进行讨论。因此,我们回顾了生物膜文献,以更好地理解这一差距。我们的搜索揭示了在适应模型中使用的表面和介质以模仿临床环境方面的实质性发展。然而,许多体外模型过于简单,通常会忽略宿主微环境的组成和特性,并忽略生物膜-植入物-宿主的相互作用。未能在体内捕获生物膜的生理生长条件导致实验室生长和临床相关生物膜之间的主要差异。特别是在表型方面,毒力,和抗菌素耐药性,它们基本上阻碍了长凳到床边的可翻译性。在这次审查中,我们描述了生物膜-植入物-宿主界面的生物过程的复杂性,讨论更好地模拟临床情景的生物膜模型的开发和表征的先决条件,并提出了如何通过融合组织工程概念和工具在体外对生物膜进行生物工程的跨学科展望。
    Biofilm research has grown exponentially over the last decades, arguably due to their contribution to hospital acquired infections when they form on foreign body surfaces such as catheters and implants. Yet, translation of the knowledge acquired in the laboratory to the clinic has been slow and/or often it is not attempted by research teams to walk the talk of what is defined as \'bench to bedside\'. We therefore reviewed the biofilm literature to better understand this gap. Our search revealed substantial development with respect to adapting surfaces and media used in models to mimic the clinical settings, however many of the in vitro models were too simplistic, often discounting the composition and properties of the host microenvironment and overlooking the biofilm-implant-host interactions. Failure to capture the physiological growth conditions of biofilms in vivo results in major differences between lab-grown- and clinically-relevant biofilms, particularly with respect to phenotypic profiles, virulence, and antimicrobial resistance, and they essentially impede bench-to-bedside translatability. In this review, we describe the complexity of the biological processes at the biofilm-implant-host interfaces, discuss the prerequisite for the development and characterization of biofilm models that better mimic the clinical scenario, and propose an interdisciplinary outlook of how to bioengineer biofilms in vitro by converging tissue engineering concepts and tools.
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  • 文章类型: Journal Article
    背景:支撑元件之间的适当载荷分布对于植入物辅助的可移动局部义齿的长期成功至关重要;但是,关于负载分布的信息很少。
    目的:本研究旨在通过回顾体外模型和有限元分析研究,评估种植体位置对种植体辅助可摘局部义齿中载荷分布的影响。
    方法:在2001年1月至2022年10月之间发表的研究种植体辅助可摘局部义齿的负荷分布的英文研究摘自PubMed,ScienceDirect,和Scopus在线数据库,手动搜索。两名审稿人根据预定的纳入和排除标准选择了文章,然后进行数据提取和分析。
    结果:在评估了264篇文章的标题和摘要后,选择了47项研究;其中两项是手动确定的。筛选文本后,包括12项研究:6项体外模型实验和6项有限元分析研究。所有纳入的研究均使用下颌游离端缺失模型(肯尼迪I级或II级)。种植体位置对基牙载荷分布的影响,植入物,并总结了三种情况:前磨牙种植,第一磨牙,和第二磨牙区。由于义齿的载荷分布和载荷条件的测量方法不同,研究结果不同。
    结论:种植体辅助可摘局部义齿中的种植体位置可影响支撑元件的载荷分布,例如基牙,植入物,和义齿基托下的粘膜。
    Appropriate load distribution among the supporting elements is essential for the long-term success of implant-assisted removable partial dentures; however, there is little information available on load distribution.
    This study aimed to evaluate the effect of implant location on load distribution in implant-assisted removable partial dentures by reviewing in vitro models and finite-element analysis studies.
    English-language studies which examined the load distribution of implant-assisted removable partial dentures and were published between January 2001 and October 2022 were extracted from PubMed, ScienceDirect, and Scopus online databases, and manual searching. Two reviewers selected the articles based on the predetermined inclusion and exclusion criteria, followed by data extraction and analysis.
    Forty-seven studies were selected after evaluating the titles and abstracts of 264 articles; two were identified manually. After screening the text, 12 studies were included: six in vitro model experiments and six finite-element analysis studies. All included studies used a mandibular free-end missing model (Kennedy Class I or II). The influence of implant location on load distribution to the abutment tooth, implant, and mucosa under the denture base was summarized in three cases: implant at the premolar, first molar, and second molar region. Due to differences in the measurement method of load distribution and loading condition to the denture, the results differed among the studies.
    The implant location in implant-assisted removable partial dentures can affect load distribution to the supporting elements, such as the abutment tooth, implant, and mucosa under the denture base.
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  • 文章类型: Review
    供应的可变性,供体的缺乏和体外条件下的细胞不稳定性限制了原代人肝细胞(PHHs)在肝毒性测试中的应用。因此,已经寻找功能性肝细胞的替代来源。许多早期的体外肝毒性研究是使用肝癌衍生的细胞系进行的。这些细胞系已经克服了PHHs在表型稳定性和可用性方面的一些局限性;然而,他们有自己固有的局限性,例如缺乏药物代谢功能,这使得它们不足以用于发生母体药物的毒性代谢物形成的情况。在过去的十年中,我们目睹了研究界对使用源自人类诱导多能干细胞(iPSC)的肝细胞样细胞(HLC)作为体外肝毒性模型的兴趣。HLCs提供功能肝细胞的定义和可再生供应的观点;更重要的是,HLCs保持其原始供体基因型并提供供体多样性,从而为患者特异性毒性测试开辟了新的途径。在这次审查中,我们首先介绍各种体外肝毒性模型,然后重点关注HLC及其在肝毒性研究中的应用,最后对该领域的未来发展提出了一些看法。
    Variability in supply, paucity of donors and cellular instability under in vitro conditions have limited the application of primary human hepatocytes (PHHs) to hepatotoxicity testing. Therefore, alternative sources have been sought for functional liver cells. Many of the earlier in vitro hepatotoxicity studies were carried out using hepatoma-derived cell lines. These cell lines have overcome some of the limitations of PHHs with regard to phenotypic stability and availability; however, they suffer from their own inherent limitations, such as the lack of drug-metabolizing functionality, which renders them inadequate for situations where toxic metabolite formation of the parent drug occurs. In the last decade we have witnessed a burgeoning interest of the research community in using hepatocyte-like cells (HLCs) derived from human induced pluripotent stem cells (iPSCs) as in vitro hepatotoxicity models. HLCs offer the perspective of a defined and renewable supply of functional hepatocytes; more importantly, HLCs maintain their original donor genotype and afford donor diversity, thus opening new avenues to patient-specific toxicity testing. In this review, we first introduce various in vitro hepatotoxicity models, then focus on HLCs and their application in hepatotoxicity studies, and finally offer some perspectives on future developments of the field.
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  • 文章类型: Systematic Review
    自1980年代初以来,许多研究人员为人类胃肠系统的体外模型的开发做出了贡献,用于肠道微生物组生态学的机械询问。使用生物反应器来模拟胃肠系统的所有特征和条件是巨大的挑战。一些条件,如温度和pH值,很容易控制,但模拟的一个更具挑战性的特征是,两者可能在胃肠道的不同区域有所不同。已经开发了用于模拟其他功能的有希望的解决方案,例如透析能力,蠕动运动,和生物膜生长。这一研究领域正在不断发展,需要进一步的努力来推动这些模型更接近体内条件,从而增加了它们对研究肠道微生物对人类健康影响的有用性。因此,了解关键操作参数的影响是完善当前生物反应器和指导开发更复杂模型的基础。在这次审查中,我们在229篇论文中对操作参数进行了系统的搜索,这些论文使用了接种人类粪便的连续生物反应器。尽管各种生物反应器模型的操作参数的报告是可变的,由于缺乏标准化,讨论了具体操作参数对肠道微生物生态学的影响,突出了当前生物反应器系统的优点和局限性。
    Since the early 1980s, multiple researchers have contributed to the development of in vitro models of the human gastrointestinal system for the mechanistic interrogation of the gut microbiome ecology. Using a bioreactor for simulating all the features and conditions of the gastrointestinal system is a massive challenge. Some conditions, such as temperature and pH, are readily controlled, but a more challenging feature to simulate is that both may vary in different regions of the gastrointestinal tract. Promising solutions have been developed for simulating other functionalities, such as dialysis capabilities, peristaltic movements, and biofilm growth. This research field is under constant development, and further efforts are needed to drive these models closer to in vivo conditions, thereby increasing their usefulness for studying the gut microbiome impact on human health. Therefore, understanding the influence of key operational parameters is fundamental for the refinement of the current bioreactors and for guiding the development of more complex models. In this review, we performed a systematic search for operational parameters in 229 papers that used continuous bioreactors seeded with human feces. Despite the reporting of operational parameters for the various bioreactor models being variable, as a result of a lack of standardization, the impact of specific operational parameters on gut microbial ecology is discussed, highlighting the advantages and limitations of the current bioreactor systems.
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  • 文章类型: Journal Article
    膀胱癌(BC)占狗中所有自发发生的癌症的约2%。在大多数情况下,它的特点是破坏性的临床过程,这强调了不断需要开发新的疾病表征和治疗方法。在过去的几年里,细胞工程的进步导致了各种犬BC体外模型的发展,正在成为体内研究的补充。在这篇文章中,我们的目的是回顾现有的犬BC体外模型的可用数据,主要关注他们的特点,在兽医学中的应用,以及优点和缺点。最常用的犬BC体外模型包括生长为粘附单层的永生化细胞系。他们提供无限的研究材料,然而,它们不能忠实地反映体内普遍存在的情况,因为空间细胞相互作用丢失了。实体瘤的三维(3D)特征与致癌作用或药物反应过程有关的重要性已导致开发出第一批可用于体外研究的犬BC3D模型。到目前为止,体外和体内研究获得的结果应一起解释。随着BC癌体外模型的复杂性不断增加,未来可能会减少以动物为基础的研究。
    Bladder cancer (BC) constitutes approximately 2% of all spontaneously occurring cancers in dogs. It is characterized by a devastating clinical course in most cases, which emphasizes a constant need for the development of novel methods of disease characterization and treatment. Over the past years, advances in cell engineering have resulted in the development of various canine in vitro models of BC, emerging as complements for in vivo research. In this article, we aimed to review the available data on existing in vitro models of canine BC, focusing primarily on their characteristics, applications in veterinary medicine, as well as advantages and disadvantages. The most commonly used in vitro models of canine BC comprise immortalized cell lines grown as adherent monolayers. They provide an unlimited supply of research material, however, they do not faithfully reflect the conditions prevailing in vivo, since the spatial cellular interactions are lost. The importance of the three-dimensional (3D) features of solid tumors in relation to carcinogenesis or drug response process has resulted in the development of the first canine 3D models of BC available for in vitro research. So far, results obtained with in vitro and in vivo research should be interpreted together. With the constantly growing complexity of in vitro models of BC cancer, animal-based research might be reduced in the future.
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  • 文章类型: Systematic Review
    UNASSIGNED:确定和分析已发表的体外基准实验,以评估用于治疗近肾腹主动脉瘤(jAAAs)的血管内技术。
    未经批准:Scopus,PubMed,和WebofScience。
    UNASSIGNED:按照PRISMA指南,在2021年3月进行了系统的文献检索。两名研究人员独立进行了标题和摘要筛选,以揭示评估jAAA血管内治疗的所有基准测试。
    未经评估:共纳入19项研究,8评估开窗(FEVAR)和11个平行移植物(PG)。FEVAR研究使用不同的定制测试设备(n=7)或3D打印模型(n=1)来分析移位和迁移阻力,错位后果和因果关系,和桥接支架径向力,耀度,疲劳,和抗断裂性。所有PG研究都使用基于有机硅的模型来分析最佳尺寸过大,密封长度,排水沟行为,可能的减少。FEVAR体外测试中的测试评估基于拔出力分析(N=5),照片评估(n=1),透视(n=1),X射线(n=4),CT分析(n=3),宏观和微观评价(n=4),透水性(n=1),和疲劳模拟器测试(n=1),而它是基于所有PG研究中的CT分析,在一项研究中添加了ECG门。最常测试的设备是Zenit(Cook)(n=7),Endurant(美敦力公司)(n=5),和排除(戈尔)(n=5)作为主要移植物,和优点V12(n=14)作为桥接装置。
    UNASSIGNED:本系统综述对评估jAAA血管内治疗的当前体外方法进行了广泛分析。基本问题已经在FEVAR和PG中进行了测试。对纳入研究的分析允许推荐最佳测试设计。体外测试是进一步阐明难以在体内研究的关注点以最终增强血管内治疗结果的潜在工具。需要未来的体外研究来评估临床实践中所有不明显使用的设备的体外性能。
    UNASSIGNED: To identify and analyze the published in vitro benchtop experiments for the assessment of endovascular techniques used for the treatment of juxtarenal abdominal aortic aneurysms (jAAAs).
    UNASSIGNED: Scopus, PubMed, and Web of Science.
    UNASSIGNED: A systematic literature search was carried out throughout March 2021 following PRISMA guidelines. Two investigators independently performed title and abstract screening to reveal all benchtop testing evaluating the endovascular treatment of jAAA.
    UNASSIGNED: A total of 19 studies were included, 8 evaluating fenestrated (FEVAR) and 11 parallel grafts (PGs). FEVAR studies used different custom testing apparatus (n=7) or 3D-printed models (n=1) to analyze dislodgement and migration resistance, misalignment consequences and causation, and bridging stents\' radial force, flareability, fatigue, and fracture resistance. All PG studies used silicone-based models to analyze optimal oversizing, sealing length, gutter behavior, and possible reduction. Test evaluation in FEVAR in vitro testing was based on pullout force analysis (N=5), photo evaluation (n=1), fluoroscopy (n=1), X-rays (n=4), CT analysis (n=3), macro- and microscopic evaluation (n=4), water permeability (n=1), and fatigue simulator testing (n=1), while it was based on CT analysis in all PG studies adding ECG-gate in one study. The most frequently tested devices were Zenit (Cook) (n=7), Endurant (Medtronic) (n=5), and Excluder (Gore) (n=5) as main grafts, and Advanta V12 (n=14) as the bridging device.
    UNASSIGNED: This systematic review presents a broad analysis of the current in vitro methods evaluating the endovascular treatment of jAAA. Fundamental issues have been benchtop tested in both FEVAR and PGs. The analysis of the included studies allowed to recommend an optimal testing design. In vitro testing is a potential tool to further elucidate points of attention hard to investigate in vivo to finally enhance the endovascular treatment outcomes. Future in vitro studies are needed to evaluate the in vitro performance of all indistinctively used devices in the clinical practice.
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  • 文章类型: Journal Article
    心力衰竭是一个主要的健康风险,由于供体器官的供应有限,越来越需要开发心脏辅助装置(CAD)。模拟循环回路(MCL)是CAD性能评估和优化的重要体外测试平台。MCL是由液压和机械组件构建的集总参数模型,旨在尽可能接近地模拟天然心血管系统(CVS)。进一步的开发合并了MCL和数值循环模型,以提高系统的灵活性和准确性;通常称为混合MCL。直到2020年9月25日,在一项文献研究中总共发现了128个MCL。发现MCL的复杂性多年来不断上升,最近的MCL不仅能够模仿健康和病理状况,但也实施了大脑,肾和冠状动脉循环和自动调节反应。此外,解剖模型的发展使得流动可视化研究成为可能。机械MCL表现出优异的可控性和可重复性,然而,通常CVS过于简化或缺乏自动监管反应。在数值MCL中,与机械试验台相比,CVS用更高阶的集总参数表示,然而,复杂的生理方面往往被简化。在混合MCL中,系统的液压部分实现了复杂的生理方面,而数值模型代表了CVS的一部分,这些部分很难由机械部件本身来表示。这篇综述旨在描述这些进展,三种类型MCL的局限性和未来发展方向。
    Heart failure is a major health risk, and with limited availability of donor organs, there is an increasing need for developing cardiac assist devices (CADs). Mock circulatory loops (MCL) are an important in-vitro test platform for CAD\'s performance assessment and optimisation. The MCL is a lumped parameter model constructed out of hydraulic and mechanical components aiming to simulate the native cardiovascular system (CVS) as closely as possible. Further development merged MCLs and numerical circulatory models to improve flexibility and accuracy of the system; commonly known as hybrid MCLs. A total of 128 MCLs were identified in a literature research until 25 September 2020. It was found that the complexity of the MCLs rose over the years, recent MCLs are not only capable of mimicking the healthy and pathological conditions, but also implemented cerebral, renal and coronary circulations and autoregulatory responses. Moreover, the development of anatomical models made flow visualisation studies possible. Mechanical MCLs showed excellent controllability and repeatability, however, often the CVS was overly simplified or lacked autoregulatory responses. In numerical MCLs the CVS is represented with a higher order of lumped parameters compared to mechanical test rigs, however, complex physiological aspects are often simplified. In hybrid MCLs complex physiological aspects are implemented in the hydraulic part of the system, whilst the numerical model represents parts of the CVS that are too difficult to represent by mechanical components per se. This review aims to describe the advances, limitations and future directions of the three types of MCLs.
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  • 文章类型: Journal Article
    Recent trends in nanoparticles-based oral therapy have led to a proliferation of studies to enhance solubility, permeability and chemical stability of many drugs. One of the significant current discussions is achieving high bioavailability of drugs poorly absorbed with an impairing coincidence of oral degradation. Solid lipid nanoparticles (SLNs), absorbed and trafficked via transcellular and paracellular pathways, are one of the utmost innovative promising nanocarriers to overwhelm drawbacks of the poorly absorbed drugs. The central topic of this review is focusing on providing brief updates on SLNs for improving drug oral absorption with their evolutions in curing numerous ailments. In order to create a new paradigm of therapeutic formulations, we also highlight the transversal mechanisms of SLNs across the gastrointestinal hurdles and a series of novel researches regarding in vitro protocols to uncover the investigations of the transmembrane absorption and transport kinetics of SLNs. The current challenges and future perspectives of SLNs for oral drug delivery are refined and forecasted. Several questions remain unanswered and it is recommended to pay a close attention to the most sophisticated in vivo-like culture practices which open new avenues to thoroughly elucidate how SLNs interact with intestinal mucosa at cellular and molecular levels. Additionally, further studies are needed to concentrate on the factors influencing the absorption efficiency, proportion of SLNs in gastrointestinal tract as well as their correlation with their loaded drug bioavailability.
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