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Modeling metastasis: engineering approaches to study the metastatic cascade 转移模型:转移级联研究的工程方法
Q1 ENGINEERING, BIOMEDICAL Pub Date : 2020-10-21 DOI: 10.1088/2516-1091/abc34f
Hawley C. Pruitt, S. Gerecht
Tumor progression and metastasis requires a complex interplay between tumor cells and their surrounding environment. Conventional 2D and 3D tissue culture models lack the precision and spatiotemporal control required to accurately model the complexity of the tumor microenvironment and metastatic cascade. Advances in biomedical engineering have allowed us to generate precise and versatile model systems to elucidate mechanisms vital to tumor progression and metastasis. The incorporation of novel biomaterials creates a specific mechanical environment that has facilitated controlled studies of cancer cell mechano-transduction. In addition, microfluidic devices have not only allowed for the incorporation of flow and shear forces into vascularized tumor models, but also elucidated vital mechanisms of cancer cell migration that have shifted paradigms about the mode in which cancer cells initiate metastasis. Here, we review the latest developments in biomedical engineering approaches to model the tumor microenvironment and metastatic cascade. We discuss how these approaches have advanced the field of cancer biology and enhanced our understanding of the mechanisms driving metastasis. We initially focus on physical and mechanical aspects of the primary microenvironment that impact tumor cell invasion. We then transition to tumor cell migration using models of tumor extracellular matrix including confined migration. Finally, we review models of intravasation/extravasation and colonization of secondary sites.
肿瘤的进展和转移需要肿瘤细胞和周围环境之间复杂的相互作用。传统的2D和3D组织培养模型缺乏精确模拟肿瘤微环境和转移级联的复杂性所需的精度和时空控制。生物医学工程的进步使我们能够产生精确和通用的模型系统来阐明肿瘤进展和转移的重要机制。新型生物材料的结合创造了一个特定的机械环境,促进了癌细胞机械转导的受控研究。此外,微流体装置不仅允许将流动和剪切力纳入血管化肿瘤模型,而且还阐明了癌细胞迁移的重要机制,改变了关于癌细胞启动转移模式的范式。在这里,我们回顾了生物医学工程方法模拟肿瘤微环境和转移级联的最新进展。我们讨论了这些方法如何推动了癌症生物学领域的发展,并增强了我们对肿瘤转移机制的理解。我们首先关注影响肿瘤细胞侵袭的初级微环境的物理和机械方面。然后我们使用肿瘤细胞外基质模型过渡到肿瘤细胞迁移,包括有限迁移。最后,我们回顾了内渗/外渗和继发部位定植的模型。
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引用次数: 0
Critical review on where CRISPR meets molecular diagnostics 评述CRISPR与分子诊断的交集
Q1 ENGINEERING, BIOMEDICAL Pub Date : 2020-10-08 DOI: 10.1088/2516-1091/abbf5e
A. Lau, C. Ren, Luke P Lee
Simple yet powerful clustered regularly-interspaced short palindromic repeats (CRISPR) technology has led to the advent of numerous developments in life sciences, biotechnology, therapeutics, and molecular diagnostics, enabled by gene editing capability. By exploiting the CRISPR-Cas system’s nucleic acid sequence detection abilities, CRISPR-based molecular diagnostics have been developed. Here, we review the development of rapid, sensitive, and inexpensive CRISPR-based molecular diagnostics. We introduce the transition of CRISPR technology to precision molecular diagnostic devices from tube to device. Next, we discuss the various nucleic acid (NA) detection methods by CRISPR. We address the importance of significant sample preparation steps for a future sample-to-answer solution, which is lacking in current CRISPR-based molecular diagnostic technology. Lastly, we discuss the extension of CRISPR-based molecular diagnostics to various critical applications. We envision CRISPR technology holds great promise for widespread use in precision NA detection applications after particular technical challenges are overcome.
简单而强大的规则间隔短回文重复序列(CRISPR)技术在基因编辑能力的推动下,在生命科学、生物技术、治疗学和分子诊断学领域取得了许多发展。通过利用CRISPR-Cas系统的核酸序列检测能力,开发了基于CRISPR的分子诊断。在这里,我们回顾了快速、灵敏和廉价的基于CRISPR的分子诊断的发展。我们介绍了CRISPR技术向精密分子诊断设备的转变,从试管到设备。接下来,我们将讨论CRISPR检测核酸(NA)的各种方法。我们讨论了重要的样本制备步骤对未来样本应答解决方案的重要性,这是当前基于CRISPR的分子诊断技术所缺乏的。最后,我们讨论了基于CRISPR的分子诊断技术在各种关键应用中的扩展。我们设想,在克服特定的技术挑战后,CRISPR技术有望在精确NA检测应用中广泛应用。
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引用次数: 17
Fundamentals of the gut for capsule engineers 太空舱工程师的肠道基础知识
Q1 ENGINEERING, BIOMEDICAL Pub Date : 2020-09-25 DOI: 10.1088/2516-1091/abab4c
L. Barducci, J. Norton, Sunandita Sarker, Sayeed Mohammed, Ryan Jones, P. Valdastri, B. Terry
The gastrointestinal (GI) tract is a complex environment comprised of the mouth, esophagus, stomach, small and large intestines, rectum and anus, which all cooperate to form the complete working GI system. Access to the GI using endoscopy has been augmented over the past several decades by swallowable diagnostic electromechanical devices, such as pill cameras. Research continues today and into the foreseeable future on new and more capable miniature devices for the purposes of systemic drug delivery, therapy, tissue biopsy, microbiome sampling, and a host of other novel ground-breaking applications. The purpose of this review is to provide engineers in this field a comprehensive reference manual of the GI environment and its complex physical, biological, and chemical characteristics so they can more quickly understand the constraints and challenges associated with developing devices for the GI space. To accomplish this, the work reviews and summarizes a broad spectrum of literature covering the main anatomical and physiological properties of the GI tract that are pertinent to successful development and operation of an electromechanical device. Each organ in the GI is discussed in this context, including the main mechanisms of digestion, chemical and mechanical processes that could impact devices, and GI motor behavior and resultant forces that may be experienced by objects as they move through the environment of the gut.
胃肠道是一个复杂的环境,由口腔、食道、胃、小肠和大肠、直肠和肛门组成,它们共同合作形成完整的胃肠道系统。在过去的几十年里,通过可吞咽的机电诊断设备,如药丸相机,增加了使用内窥镜检查胃肠道的机会。在可预见的未来,研究人员将继续研究新的、功能更强的微型设备,用于全身药物输送、治疗、组织活检、微生物组采样和许多其他新颖的突破性应用。本综述的目的是为该领域的工程师提供GI环境及其复杂的物理、生物和化学特性的综合参考手册,以便他们能够更快地了解与开发GI空间设备相关的限制和挑战。为了实现这一目标,本研究回顾和总结了广泛的文献,这些文献涵盖了胃肠道的主要解剖和生理特性,这些特性与机电设备的成功开发和操作有关。在此背景下讨论了胃肠道中的每个器官,包括消化的主要机制,可能影响设备的化学和机械过程,以及胃肠道运动行为和物体在肠道环境中移动时可能经历的合力。
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引用次数: 19
The magic bullet as cancer therapeutic—has nanotechnology failed to find its mark? 癌症治疗药物纳米技术的灵丹妙药没有找到它的标记?
Q1 ENGINEERING, BIOMEDICAL Pub Date : 2020-09-24 DOI: 10.1088/2516-1091/abb008
G. Xiong, K. Venkatraman, S. Venkatraman
Ever since the term ‘Magic Bullet’ was coined by Nobel laureate Paul Ehrlich to denote selective activity of a therapeutic medicine against a particular target tissue or organism, researchers have been attempting to develop the concept, with the major part of the work directed towards cancer targets. In this review, we define four major technologies that embody the Magic Bullet concept, and discuss the status of the therapeutic in each case. The reasons for relative success and failure of the four technologies are assessed based on the clinical outcomes. There have been failures of ancillary concepts (to enable selectivity) such as the enhanced permeation and retention effect, which will be discussed in context. The outlook is hopeful, with the advent of immunotherapies, that the idealized Magic Bullet will see the light of day in the near future.
自从诺贝尔奖获得者保罗·埃利希创造了“灵丹妙药”一词来表示治疗药物对特定靶组织或生物体的选择性活性以来,研究人员一直在尝试发展这一概念,其主要工作是针对癌症靶点。在这篇综述中,我们定义了体现魔术子弹概念的四种主要技术,并讨论了每种情况下的治疗现状。根据临床结果评估这四种技术相对成功和失败的原因。辅助概念(实现选择性)已经失败,例如增强的渗透和保留效应,这将在上下文中讨论。随着免疫疗法的出现,人们对理想化的灵丹妙药将在不久的将来重见天日充满希望。
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引用次数: 5
Interdisciplinary approaches to advanced cardiovascular tissue engineering: ECM-based biomaterials, 3D bioprinting, and its assessment 先进心血管组织工程的跨学科方法:基于ecm的生物材料,生物3D打印及其评估
Q1 ENGINEERING, BIOMEDICAL Pub Date : 2020-09-24 DOI: 10.1088/2516-1091/abb211
U. Yong, Sooyeon Lee, Seungman Jung, Jinah Jang
As a class of representative intractable diseases, cardiovascular disease (CVD) is the most common cause of global mortality, accounting for approximately 17.9 million deaths each year. At the end of the disease stage, surgery for replacement of cardiovascular (CV) tissue is inevitably required due to the limited regeneration capacity of CV tissue. However, the currently available methods (e.g. autografts, allografts, xenografts, prostheses) have limited therapeutic efficacy because of donor shortage, immunological transplant rejection, anticoagulant therapy, and less durability. To overcome these limitations, CV tissue engineering technology has been extensively explored to develop replaceable tissue and organs for in vivo transplantation. In addition, 3D tissue models are also studied for in vitro mechanistic study and therapeutic screening. To accomplish this, there has been tremendous progress in studying various CV tissue-specific biomaterials and advanced 3D bioprinting techniques to enhance the physiological and anatomical relevance of engineered CV tissues. Moreover, a variety of evaluation methods have been investigated to validate the unique structural properties and electrical activity of the engineered CV tissues towards non- or less-invasive and real-time assessments in 3D volumetric structures. In this review, we systemically present and discuss the advantages and applications of CV tissue-specific biomaterials, 3D bioprinting techniques, and assessment methods that can facilitate real-time monitoring. A thorough understanding of advanced strategies in CV tissue engineering can be utilized to guide work on next-generation therapeutics for CVD.
心血管疾病作为一类具有代表性的顽固性疾病,是全球最常见的死亡原因,每年约有1790万人死亡。在疾病阶段结束时,由于心血管组织的再生能力有限,不可避免地需要进行心血管(CV)组织置换手术。然而,目前可用的方法(如自体移植物、同种异体移植物、异种移植物、假体)由于供体短缺、免疫移植排斥反应、抗凝治疗和耐久性较差,治疗效果有限。为了克服这些限制,CV组织工程技术已被广泛探索,以开发用于体内移植的可替代组织和器官。此外,3D组织模型也被研究用于体外机制研究和治疗筛选。为了实现这一目标,在研究各种CV组织特异性生物材料和先进的3D生物打印技术以增强工程CV组织的生理和解剖相关性方面取得了巨大进展。此外,已经研究了各种评估方法,以验证工程CV组织的独特结构特性和电活性,从而在三维体积结构中进行无创或微创的实时评估。在这篇综述中,我们系统地介绍和讨论了CV组织特异性生物材料、3D生物打印技术以及有助于实时监测的评估方法的优势和应用。对心血管组织工程先进策略的深入了解可用于指导下一代心血管疾病治疗方法的工作。
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引用次数: 8
Optical spectroscopy for in vivo medical diagnosis—a review of the state of the art and future perspectives 光谱学在体内医学诊断中的应用——技术现状和未来展望综述
Q1 ENGINEERING, BIOMEDICAL Pub Date : 2020-08-26 DOI: 10.1088/2516-1091/abaaa3
J. Kim, D. Wales, Guang‐Zhong Yang
When light is incident to a biological tissue surface, combinations of optical processes occur, such as reflection, absorption, elastic and non-elastic scattering, and fluorescence. Analysis of these light interactions with the tissue provides insight into the metabolic and pathological state of the tissue. Furthermore, in vivo diagnosis of diseases using optical spectroscopy enables in situ rapid clinical decisions without invasive biopsies. For in vivo scenarios, incident light can be delivered in a highly localized manner to tissue via optical fibers, which are placed within the working channels of minimally invasive clinical tools, such as endoscopes. There has been extensive development in the accuracy and specificity of these optical spectroscopy techniques since the earliest in vivo examples were published in the academic literature in the early ‘90s, and there are now commercially available systems that have undergone medical and clinical trials. In this review, several types of optical spectroscopy techniques (elastic optical scattering spectroscopy, fluorescence spectroscopy, Raman spectroscopy, and multimodal spectroscopy) for the diagnosis and monitoring of diseases states of tissue in an in vivo setting are introduced and explored. Examples of the latest and most impactful works for each technique are then critically reviewed. Finally, current challenges and unmet clinical needs are discussed, followed by future opportunities, such as point-based spectroscopies for robot-guided surgical interventions.
当光入射到生物组织表面时,发生光学过程的组合,例如反射、吸收、弹性和非弹性散射以及荧光。对这些光与组织的相互作用的分析提供了对组织代谢和病理状态的深入了解。此外,使用光学光谱对疾病进行体内诊断能够在没有侵入性活检的情况下进行原位快速临床决策。对于体内场景,入射光可以通过光纤以高度局部化的方式传递到组织,光纤放置在微创临床工具(如内窥镜)的工作通道内。自从90年代初最早的体内实例发表在学术文献中以来,这些光谱技术的准确性和特异性已经得到了广泛的发展,现在已经有经过医学和临床试验的商用系统。在这篇综述中,介绍和探索了几种类型的光谱技术(弹性光学散射光谱、荧光光谱、拉曼光谱和多峰光谱),用于在体内环境中诊断和监测组织的疾病状态。然后对每种技术的最新和最具影响力的作品的例子进行批判性的回顾。最后,讨论了当前的挑战和未满足的临床需求,以及未来的机会,如机器人引导手术干预的基于点的光谱学。
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引用次数: 31
Challenges of continuum robots in clinical context: a review 连续体机器人在临床环境中的挑战:综述
Q1 ENGINEERING, BIOMEDICAL Pub Date : 2020-08-03 DOI: 10.1088/2516-1091/ab9f41
Tomás da Veiga, J. Chandler, P. Lloyd, G. Pittiglio, N. J. Wilkinson, A. K. Hoshiar, R. Harris, P. Valdastri
With the maturity of surgical robotic systems based on traditional rigid-link principles, the rate of progress slowed as limits of size and controllable degrees of freedom were reached. Continuum robots came with the potential to deliver a step change in the next generation of medical devices, by providing better access, safer interactions and making new procedures possible. Over the last few years, several continuum robotic systems have been launched commercially and have been increasingly adopted in hospitals. Despite the clear progress achieved, continuum robots still suffer from design complexity hindering their dexterity and scalability. Recent advances in actuation methods have looked to address this issue, offering alternatives to commonly employed approaches. Additionally, continuum structures introduce significant complexity in modelling, sensing, control and fabrication; topics which are of particular focus in the robotics community. It is, therefore, the aim of the presented work to highlight the pertinent areas of active research and to discuss the challenges to be addressed before the potential of continuum robots as medical devices may be fully realised.
随着基于传统刚杆原理的手术机器人系统的成熟,随着尺寸和可控自由度的限制,其发展速度减慢。Continuum机器人通过提供更好的访问、更安全的交互和使新程序成为可能,具有在下一代医疗设备中实现跨越式变化的潜力。在过去的几年里,几个连续体机器人系统已经投入商业应用,并越来越多地应用于医院。尽管取得了明显的进展,连续体机器人仍然受到设计复杂性的影响,阻碍了它们的灵活性和可扩展性。最近在驱动方法方面的进展已经解决了这个问题,为常用的方法提供了替代方案。此外,连续体结构在建模、传感、控制和制造方面引入了显著的复杂性;机器人社区特别关注的主题。因此,本文的目的是强调积极研究的相关领域,并讨论在连续体机器人作为医疗设备的潜力得到充分实现之前需要解决的挑战。
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引用次数: 100
Biochemomechanics of the thoracic aorta in health and disease 健康与疾病中胸主动脉的生物化学力学
Q1 ENGINEERING, BIOMEDICAL Pub Date : 2020-07-07 DOI: 10.1088/2516-1091/ab9a29
Selda Sherifova and, G. Holzapfel
Aneurysms and dissections of the thoracic aorta are life threatening events with poorly understood pathophysiologies which may have genetic origins. By starting with an introduction to these pathologies, we focus on the biochemomechanics of the healthy thoracic aorta. Specifically, we describe the microstructure and the mechanics of the aortic tissue since it is known that the microstructure strongly influences the biomechanical behavior. This relationship is then complemented by providing more detailed information on the selected extracellular matrix components (collagen, elastic fibers and proteoglycans) and smooth muscle cells. More specifically, we introduce the roles smooth muscle cells play in the function of the aortic wall: actively (mechanically) with their contractile abilities and passively by regulating the composition of the extracellular matrix they are embedded in, in particular via the transforming growth factor β (TGF-β) pathway. Subsequently, we summarize the microstructural changes in thoracic aortic aneurysms and dissections in connection with selected risk factors and genetic mutations, and couple these changes with the findings on the biomechanical behavior of the pathological tissues. Finally, we provide a summary and concluding remarks.
动脉瘤和胸主动脉夹层是危及生命的事件,其病理生理学知之甚少,可能有遗传起源。通过对这些病理学的介绍,我们将重点关注健康胸主动脉的生物化学机制。具体来说,我们描述了主动脉组织的微观结构和力学,因为众所周知,微观结构对生物力学行为有很大影响。然后通过提供关于所选细胞外基质成分(胶原蛋白、弹性纤维和蛋白聚糖)和平滑肌细胞的更详细信息来补充这种关系。更具体地说,我们介绍了平滑肌细胞在主动脉壁功能中的作用:主动(机械地)发挥其收缩能力,被动地通过调节其嵌入的细胞外基质的组成,特别是通过转化生长因子β(TGF-β)途径。随后,我们总结了胸主动脉瘤和夹层的微观结构变化与选定的危险因素和基因突变有关,并将这些变化与病理组织的生物力学行为相结合。最后,我们提供一个总结和结束语。
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引用次数: 13
Catheter-based optical approaches for cardiovascular medicine: progress, challenges and new directions 基于导管的心血管医学光学方法:进展、挑战和新方向
Q1 ENGINEERING, BIOMEDICAL Pub Date : 2020-06-12 DOI: 10.1088/2516-1091/ab8af8
Chao Huang, Nathan J. Knighton, L. Timmins, F. Sachse
Catheterization of the heart is crucial for many diagnostic and therapeutic procedures in cardiovascular medicine. In this review, we discussed developments of catheter-based optical tools and approaches for cardiovascular medicine. We provided a background in gross and microscopic anatomy of the normal and diseased heart. We overviewed optical properties of cardiac tissues, such as scattering, absorption and fluorescence, and related optical properties to tissues constituents. Furthermore, we introduced optical modalities for tissue characterization, in particular, spectroscopy, confocal, multi-photon and light sheet fluorescence microcopy, and optical coherence tomography. We then surveyed example applications in cardiovascular medicine and contrasted established clinical tools and approaches with catheter-based optical approaches and tools. First, we explored assessment of heart transplant rejection and reviewed alternative catheterized optical approaches. Rejection is commonly assessed using endomyocardial biopsy, i.e. the excision and histological assessment of tissue samples. A further application is atrial fibrosis mapping. Atrial fibrosis is an important predictor for prognosis of atrial fibrillation patients, yet clinical tools for fibrosis mapping in patients are lacking. We surveyed clinical tools for assessing catheter ablation of the heart, which is an indispensable therapy for arrhythmia. Last, we discussed methods and protocols for guiding coronary angioplasty and stent placement. For all applications, we explored the current and potential role of catheterized optical tools. We concluded with a discussion of technical challenges and open questions related to clinical translation of the catheter-based optical approaches. Our review stressed the potential of catheterized optical tools to improve diagnosis and treatment of patients with heart disease.
在心血管医学的许多诊断和治疗程序中,心脏导管是至关重要的。在这篇综述中,我们讨论了心血管医学中基于导管的光学工具和方法的发展。我们提供了正常和患病心脏的大体和微观解剖背景。我们综述了心脏组织的光学性质,如散射、吸收和荧光,以及与组织成分相关的光学性质。此外,我们还介绍了用于组织表征的光学模式,特别是光谱学、共焦、多光子和光片荧光显微镜以及光学相干断层扫描。然后,我们调查了心血管医学中的应用实例,并将已建立的临床工具和方法与基于导管的光学方法和工具进行了对比。首先,我们探讨了心脏移植排斥反应的评估,并回顾了可供选择的导管光学方法。排斥反应通常使用心肌内活检进行评估,即组织样本的切除和组织学评估。进一步的应用是心房纤维化标测。心房纤维化是心房颤动患者预后的重要预测指标,但缺乏对患者进行纤维化标测的临床工具。我们调查了评估心脏导管消融的临床工具,这是心律失常不可或缺的治疗方法。最后,我们讨论了引导冠状动脉血管成形术和支架置入的方法和方案。对于所有应用,我们探索了导管光学工具的当前和潜在作用。最后,我们讨论了与基于导管的光学方法的临床翻译相关的技术挑战和悬而未决的问题。我们的综述强调了导管光学工具在改善心脏病患者诊断和治疗方面的潜力。
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引用次数: 3
Introducing Progress in Biomedical Engineering; Issue 2 Vol 2 生物医学工程进展介绍;第2期第2卷
Q1 ENGINEERING, BIOMEDICAL Pub Date : 2020-05-27 DOI: 10.1088/2516-1091/ab871a
M. Sitti
Progress in Biomedical Engineering is a new interdisciplinary journal publishing high-quality authoritative reviews and opinion pieces in the most significant and exciting areas of biomedical engineering research. Invited content by leading experts on the current state of the science and emerging trends aims to fuel discussion on the future direction of research. In our first and second issues this year, we have four topical review articles. In the first review article related to medical devices, Xia et al present and discuss intravascular sensors to assess unstable plaques and their compositions. Vulnerable atherosclerotic plaques can rapture, which can create acute cardiovascular events and sudden cardiac deaths as a major health issue all around the world. Existing methods such as coronary angiography lacks the capacity to provide detailed information about exact lipid-rich, fibrotic or calcified type of properties of the lesion. Therefore, novel catheter technologies have been proposed for the assessment of atherosclerotic plaques, which integrates intravascular ultrasound with photoacoustic microscopy or optical coherence tomography and utilizes stretchable electrodes for electrochemical impedance spectroscopy. While these technologies are promising for the identification of the complexity and composition of potentially unstable plaques in animal and human trials, real-time detection of such plaques in clinics is still a significant challenge. This article highlights existing and emerging intravascular sensors to assess unstable plaques and their compositions. The authors report the advantages, limitations, future directions, and potential clinical applications of such sensors. the fundamentals and state-of-the-art the future of vascularization of engineered tissues, which is a grand challenge in engineering regenerative A new recent tissue engineering sub-field, called vascular tissue engineering, to a
《生物医学工程进展》是一本新的跨学科期刊,在生物医学工程研究的最重要和最令人兴奋的领域发表高质量的权威评论和观点文章。主要专家邀请的关于科学现状和新兴趋势的内容旨在推动对未来研究方向的讨论。在今年的第一期和第二期中,我们有四篇专题评论文章。在第一篇与医疗器械相关的综述文章中,Xia等人介绍并讨论了血管内传感器来评估不稳定斑块及其成分。脆弱的动脉粥样硬化斑块可能会破裂,这可能会导致急性心血管事件和心脏性猝死,这是世界各地的一个主要健康问题。现有的方法,如冠状动脉造影,缺乏提供关于确切的富含脂质、纤维化或钙化类型的病变特性的详细信息的能力。因此,已经提出了用于评估动脉粥样硬化斑块的新型导管技术,该技术将血管内超声与光声显微镜或光学相干断层扫描相结合,并利用可拉伸电极进行电化学阻抗谱。尽管这些技术有望在动物和人体试验中识别潜在不稳定斑块的复杂性和组成,但在诊所中实时检测此类斑块仍然是一个重大挑战。本文重点介绍了现有和新兴的血管内传感器,用于评估不稳定斑块及其成分。作者报告了这种传感器的优点、局限性、未来方向和潜在的临床应用。工程组织血管化的基本原理和最新技术,这是工程再生中的一个巨大挑战。一个新的组织工程子领域,称为血管组织工程
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引用次数: 0
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Progress in biomedical engineering (Bristol, England)
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