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Digital Manufacturing for Microfluidics. 微流体的数字化制造。
IF 9.7 1区 工程技术 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2019-06-04 DOI: 10.1146/annurev-bioeng-092618-020341
Arman Naderi, Nirveek Bhattacharjee, Albert Folch

The microfluidics field is at a critical crossroads. The vast majority of microfluidic devices are presently manufactured using micromolding processes that work very well for a reduced set of biocompatible materials, but the time, cost, and design constraints of micromolding hinder the commercialization of many devices. As a result, the dissemination of microfluidic technology-and its impact on society-is in jeopardy. Digital manufacturing (DM) refers to a family of computer-centered processes that integrate digital three-dimensional (3D) designs, automated (additive or subtractive) fabrication, and device testing in order to increase fabrication efficiency. Importantly, DM enables the inexpensive realization of 3D designs that are impossible or very difficult to mold. The adoption of DM by microfluidic engineers has been slow, likely due to concerns over the resolution of the printers and the biocompatibility of the resins. In this article, we review and discuss the various printer types, resolution, biocompatibility issues, DM microfluidic designs, and the bright future ahead for this promising, fertile field.

微流控领域正处于一个关键的十字路口。目前,绝大多数微流控装置都是使用微成型工艺制造的,这种工艺对生物相容性材料的减少效果非常好,但是时间、成本和微成型的设计限制阻碍了许多设备的商业化。因此,微流控技术的传播及其对社会的影响处于危险之中。数字制造(DM)是指一系列以计算机为中心的过程,这些过程集成了数字三维(3D)设计、自动化(增材或减材)制造和设备测试,以提高制造效率。重要的是,DM可以实现不可能或非常难以成型的廉价3D设计。微流控工程师对DM的采用进展缓慢,可能是由于对打印机分辨率和树脂生物相容性的担忧。在本文中,我们回顾和讨论了各种打印机类型,分辨率,生物相容性问题,DM微流控设计,以及这一充满希望的肥沃领域的光明前景。
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引用次数: 56
Frontiers of Medical Robotics: From Concept to Systems to Clinical Translation. 医学机器人的前沿:从概念到系统到临床翻译。
IF 9.7 1区 工程技术 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2019-06-04 Epub Date: 2019-03-01 DOI: 10.1146/annurev-bioeng-060418-052502
Jocelyne Troccaz, Giulio Dagnino, Guang-Zhong Yang

Medical robotics is poised to transform all aspects of medicine-from surgical intervention to targeted therapy, rehabilitation, and hospital automation. A key area is the development of robots for minimally invasive interventions. This review provides a detailed analysis of the evolution of interventional robots and discusses how the integration of imaging, sensing, and robotics can influence the patient care pathway toward precision intervention and patient-specific treatment. It outlines how closer coupling of perception, decision, and action can lead to enhanced dexterity, greater precision, and reduced invasiveness. It provides a critical analysis of some of the key interventional robot platforms developed over the years and their relative merit and intrinsic limitations. The review also presents a future outlook for robotic interventions and emerging trends in making them easier to use, lightweight, ergonomic, and intelligent, and thus smarter, safer, and more accessible for clinical use.

医疗机器人将改变医学的各个方面——从手术干预到靶向治疗、康复和医院自动化。一个关键领域是开发用于微创干预的机器人。本文对介入机器人的发展进行了详细的分析,并讨论了成像、传感和机器人技术的集成如何影响患者护理途径,以实现精确干预和患者特异性治疗。它概述了如何将感知、决策和行动更紧密地结合在一起,从而提高灵活性、精确度和减少侵入性。它提供了一些关键的介入机器人平台的关键分析,多年来发展和他们的相对优点和内在的局限性。该综述还介绍了机器人干预的未来前景,以及使其更易于使用、重量轻、符合人体工程学和智能化的新兴趋势,从而更智能、更安全、更易于临床使用。
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引用次数: 81
Challenges and Opportunities in the Design of Liver-on-Chip Microdevices. 肝脏片上微器件设计的挑战与机遇。
IF 9.7 1区 工程技术 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2019-06-04 DOI: 10.1146/annurev-bioeng-060418-052305
Avner Ehrlich, Daniel Duche, Gladys Ouedraogo, Yaakov Nahmias

The liver is the central hub of xenobiotic metabolism and consequently the organ most prone to cosmetic- and drug-induced toxicity. Failure to detect liver toxicity or to assess compound clearance during product development is a major cause of postmarketing product withdrawal, with disastrous clinical and financial consequences. While small animals are still the preferred model in drug development, the recent ban on animal use in the European Union created a pressing need to develop precise and efficient tools to detect human liver toxicity during cosmetic development. This article includes a brief review of liver development, organization, and function and focuses on the state of the art of long-term cell culture, including hepatocyte cell sources, heterotypic cell-cell interactions, oxygen demands, and culture medium formulation. Finally, the article reviews emerging liver-on-chip devices and discusses the advantages and pitfalls of individual designs. The goal of this review is to provide a framework to design liver-on-chip devices and criteria with which to evaluate this emerging technology.

肝脏是外源代谢的中心枢纽,因此是最容易发生美容和药物毒性的器官。在产品开发期间未能检测肝毒性或评估化合物清除是上市后产品撤回的主要原因,具有灾难性的临床和财务后果。虽然小动物仍然是药物开发的首选模型,但最近欧盟禁止动物使用,迫切需要开发精确有效的工具来检测化妆品开发过程中的人体肝脏毒性。本文简要回顾了肝脏的发育、组织和功能,并重点介绍了长期细胞培养的最新进展,包括肝细胞来源、异型细胞-细胞相互作用、氧需求和培养基配方。最后,文章回顾了新兴的肝片器件,并讨论了个别设计的优点和缺陷。本综述的目的是提供一个设计肝脏芯片设备的框架和评估这一新兴技术的标准。
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引用次数: 66
The Meniscus in Normal and Osteoarthritic Tissues: Facing the Structure Property Challenges and Current Treatment Trends. 正常和骨关节炎组织中的半月板:面临结构特性挑战和当前治疗趋势。
IF 9.7 1区 工程技术 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2019-06-04 Epub Date: 2019-04-08 DOI: 10.1146/annurev-bioeng-060418-052547
Caroline A Murphy, Atul K Garg, Joana Silva-Correia, Rui L Reis, Joaquim M Oliveira, Maurice N Collins

The treatment of meniscus injuries has recently been facing a paradigm shift toward the field of tissue engineering, with the aim of regenerating damaged and diseased menisci as opposed to current treatment techniques. This review focuses on the structure and mechanics associated with the meniscus. The meniscus is defined in terms of its biological structure and composition. Biomechanics of the meniscus are discussed in detail, as an understanding of the mechanics is fundamental for the development of new meniscal treatment strategies. Key meniscal characteristics such as biological function, damage (tears), and disease are critically analyzed. The latest technologies behind meniscal repair and regeneration are assessed.

半月板损伤的治疗最近正面临着向组织工程领域的范式转变,其目的是再生受损和患病的半月板,而不是目前的治疗技术。本文综述了与半月板相关的结构和力学。半月板是根据其生物结构和组成来定义的。详细讨论了半月板的生物力学,因为了解力学是发展新的半月板治疗策略的基础。关键的半月板特征,如生物功能,损伤(撕裂),和疾病进行严格的分析。评估了半月板修复和再生背后的最新技术。
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引用次数: 52
Single-Cell Omics Analyses Enabled by Microchip Technologies. 微芯片技术支持单细胞组学分析。
IF 9.7 1区 工程技术 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2019-06-04 Epub Date: 2019-03-18 DOI: 10.1146/annurev-bioeng-060418-052538
Yanxiang Deng, Amanda Finck, Rong Fan

Single-cell omics studies provide unique information regarding cellular heterogeneity at various levels of the molecular biology central dogma. This knowledge facilitates a deeper understanding of how underlying molecular and architectural changes alter cell behavior, development, and disease processes. The emerging microchip-based tools for single-cell omics analysis are enabling the evaluation of cellular omics with high throughput, improved sensitivity, and reduced cost. We review state-of-the-art microchip platforms for profiling genomics, epigenomics, transcriptomics, proteomics, metabolomics, and multi-omics at single-cell resolution. We also discuss the background of and challenges in the analysis of each molecular layer and integration of multiple levels of omics data, as well as how microchip-based methodologies benefit these fields. Additionally, we examine the advantages and limitations of these approaches. Looking forward, we describe additional challenges and future opportunities that will facilitate the improvement and broad adoption of single-cell omics in life science and medicine.

单细胞组学研究在分子生物学中心教条的各个层面上提供了关于细胞异质性的独特信息。这些知识有助于更深入地了解潜在的分子和结构变化如何改变细胞行为、发育和疾病过程。新兴的基于微芯片的单细胞组学分析工具使细胞组学的评估具有高通量,提高灵敏度和降低成本。我们回顾了在单细胞分辨率下分析基因组学、表观基因组学、转录组学、蛋白质组学、代谢组学和多组学的最先进的微芯片平台。我们还讨论了分析每个分子层和整合多个层次组学数据的背景和挑战,以及基于微芯片的方法如何使这些领域受益。此外,我们还研究了这些方法的优点和局限性。展望未来,我们描述了更多的挑战和未来的机遇,这些挑战和机遇将促进单细胞组学在生命科学和医学中的改进和广泛采用。
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引用次数: 42
Biomaterials: Been There, Done That, and Evolving into the Future. 生物材料:去过那里,做过那件事,并进化到未来。
IF 9.7 1区 工程技术 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2019-06-04 DOI: 10.1146/annurev-bioeng-062117-120940
Buddy D Ratner

Biomaterials as we know them today had their origins in the late 1940s with off-the-shelf commercial polymers and metals. The evolution of materials for medical applications from these simple origins has been rapid and impactful. This review relates some of the early history; addresses concerns after two decades of development in the twenty-first century; and discusses how advanced technologies in both materials science and biology will address concerns, advance materials used at the biointerface, and improve outcomes for patients.

我们今天所知道的生物材料起源于20世纪40年代末,当时是现成的商业聚合物和金属。从这些简单的起源开始,医学应用材料的发展迅速而有影响力。本文回顾了一些早期的历史;解决二十一世纪经过二十年发展后的关切;并讨论了材料科学和生物学的先进技术将如何解决问题,在生物界面上使用先进的材料,并改善患者的治疗效果。
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引用次数: 65
Hydrogel-Based Strategies to Advance Therapies for Chronic Skin Wounds. 基于水凝胶的策略推进慢性皮肤伤口的治疗。
IF 9.7 1区 工程技术 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2019-06-04 Epub Date: 2019-03-01 DOI: 10.1146/annurev-bioeng-060418-052422
Lucília P da Silva, Rui L Reis, Vitor M Correlo, Alexandra P Marques

Chronic skin wounds are the leading cause of nontraumatic foot amputations worldwide and present a significant risk of morbidity and mortality due to the lack of efficient therapies. The intrinsic characteristics of hydrogels allow them to benefit cutaneous healing essentially by supporting a moist environment. This property has long been explored in wound management to aid in autolytic debridement. However, chronic wounds require additional therapeutic features that can be provided by a combination of hydrogels with biochemical mediators or cells, promoting faster and better healing. We survey hydrogel-based approaches with potential to improve the healing of chronic wounds by reviewing their effects as observed in preclinical models. Topics covered include strategies to ablate infection and resolve inflammation, the delivery of bioactive agents to accelerate healing, and tissue engineering approaches for skin regeneration. The article concludes by considering the relevance of treating chronic skin wounds using hydrogel-based strategies.

慢性皮肤伤口是世界范围内非创伤性足部截肢的主要原因,由于缺乏有效的治疗方法,它具有显著的发病率和死亡率风险。水凝胶的内在特性使它们有利于皮肤愈合,主要是通过支持潮湿的环境。长期以来,人们一直在伤口管理中探索这一特性,以帮助进行自溶性清创。然而,慢性伤口需要额外的治疗功能,可以通过水凝胶与生化介质或细胞的组合来提供,促进更快更好的愈合。我们调查了基于水凝胶的方法,通过回顾它们在临床前模型中观察到的效果,有可能改善慢性伤口的愈合。主题包括消融感染和消炎的策略,加速愈合的生物活性剂的输送,以及皮肤再生的组织工程方法。文章最后考虑了使用基于水凝胶的策略治疗慢性皮肤伤口的相关性。
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引用次数: 100
Human Positron Emission Tomography Neuroimaging. 人体正电子发射断层扫描神经成像。
IF 9.7 1区 工程技术 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2019-06-04 DOI: 10.1146/annurev-bioeng-062117-121056
Jacob M Hooker, Richard E Carson

Neuroimaging with positron emission tomography (PET) is the most powerful tool for understanding pharmacology, neurochemistry, and pathology in the living human brain. This technology combines high-resolution scanners to measure radioactivity throughout the human body with specific, targeted radioactive molecules, which allow measurements of a myriad of biological processes in vivo. While PET brain imaging has been active for almost 40 years, the pace of development for neuroimaging tools, known as radiotracers, and for quantitative analytical techniques has increased dramatically over the past decade. Accordingly, the fundamental questions that can be addressed with PET have expanded in basic neurobiology, psychiatry, neurology, and related therapeutic development. In this review, we introduce the field of human PET neuroimaging, some of its conceptual underpinnings, and motivating questions. We highlight some of the more recent advances in radiotracer development, quantitative modeling, and applications of PET to the study of the human brain.

神经成像与正电子发射断层扫描(PET)是最强大的工具,了解药理学,神经化学和病理在活人的大脑。这项技术结合了高分辨率扫描仪,通过特定的靶向放射性分子来测量整个人体的放射性,从而可以测量体内无数的生物过程。虽然PET脑成像已经活跃了近40年,但在过去的十年里,神经成像工具(即放射性示踪剂)和定量分析技术的发展速度也在急剧增加。因此,PET可以解决的基本问题已经扩展到基础神经生物学、精神病学、神经病学和相关治疗发展。在这篇综述中,我们介绍了人类PET神经成像领域,它的一些概念基础和激励问题。我们重点介绍了放射性示踪剂开发、定量建模和PET在人脑研究中的应用方面的一些最新进展。
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引用次数: 35
The Driving Force: Nuclear Mechanotransduction in Cellular Function, Fate, and Disease. 驱动力:细胞功能、命运和疾病中的核机制传导。
IF 12.8 1区 工程技术 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2019-06-04 Epub Date: 2019-03-27 DOI: 10.1146/annurev-bioeng-060418-052139
Melanie Maurer, Jan Lammerding

Cellular behavior is continuously affected by microenvironmental forces through the process of mechanotransduction, in which mechanical stimuli are rapidly converted to biochemical responses. Mounting evidence suggests that the nucleus itself is a mechanoresponsive element, reacting to cytoskeletal forces and mediating downstream biochemical responses. The nucleus responds through a host of mechanisms, including partial unfolding, conformational changes, and phosphorylation of nuclear envelope proteins; modulation of nuclear import/export; and altered chromatin organization, resulting in transcriptional changes. It is unclear which of these events present direct mechanotransduction processes and which are downstream of other mechanotransduction pathways. We critically review and discuss the current evidence for nuclear mechanotransduction, particularly in the context of stem cell fate, a largely unexplored topic, and in disease, where an improved understanding of nuclear mechanotransduction is beginning to open new treatment avenues. Finally, we discuss innovative technological developments that will allow outstanding questions in the rapidly growing field of nuclear mechanotransduction to be answered.

细胞行为通过机械传导过程不断受到微环境力的影响,在这一过程中,机械刺激迅速转化为生化反应。越来越多的证据表明,细胞核本身就是一种机械传导元件,它能对细胞骨架力做出反应,并介导下游生化反应。细胞核通过一系列机制做出反应,包括核包膜蛋白的部分解折、构象变化和磷酸化;核输入/输出调节;染色质组织改变,导致转录变化。目前还不清楚这些事件中哪些是直接的机械传导过程,哪些是其他机械传导途径的下游。我们批判性地回顾和讨论了核机械传导的现有证据,特别是在干细胞命运(这是一个基本未探索的课题)和疾病方面,对核机械传导的深入了解正开始开辟新的治疗途径。最后,我们讨论了创新技术的发展,这些发展将使迅速发展的核机械传导领域中悬而未决的问题得到解答。
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引用次数: 0
Skin-Mountable Biosensors and Therapeutics: A Review. 皮肤贴装式生物传感器及其治疗方法综述。
IF 9.7 1区 工程技术 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2019-06-04 Epub Date: 2019-03-18 DOI: 10.1146/annurev-bioeng-060418-052315
Eun Kwang Lee, Min Ku Kim, Chi Hwan Lee

Miniaturization of electronic components and advances in flexible and stretchable materials have stimulated the development of wearable health care systems that can reflect and monitor personal health status by health care professionals. New skin-mountable devices that offer seamless contact onto the human skin, even under large deformations by natural motions of the wearer, provide a route for both high-fidelity monitoring and patient-controlled therapy. This article provides an overview of several important aspects of skin-mountable devices and their applications in many medical settings and clinical practices. We comprehensively describe various transdermal sensors and therapeutic systems that are capable of detecting physical, electrophysiological, and electrochemical responses and/or providing electrical and thermal therapies and drug delivery services, and we discuss the current challenges, opportunities, and future perspectives in the field. Finally, we present ways to protect the embedded electronic components of skin-mountable devices from the environment by use of mechanically soft packaging materials.

电子元件的小型化和柔性和可拉伸材料的进步刺激了可穿戴医疗保健系统的发展,这些系统可以反映和监测医疗保健专业人员的个人健康状况。新的皮肤贴装设备可以无缝接触人体皮肤,即使在佩戴者自然运动造成的大变形下,也可以提供高保真监测和患者控制治疗的途径。本文概述了皮肤贴装装置的几个重要方面及其在许多医疗环境和临床实践中的应用。我们全面描述了各种透皮传感器和治疗系统,它们能够检测物理、电生理和电化学反应,并/或提供电、热疗法和药物递送服务,我们讨论了该领域当前的挑战、机遇和未来的前景。最后,我们提出了通过使用机械软包装材料来保护皮肤贴装设备的嵌入式电子元件免受环境影响的方法。
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引用次数: 39
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Annual Review of Biomedical Engineering
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