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Kidney Disease Modeling with Organoids and Organs-on-Chips. 利用有机体和芯片器官建立肾脏疾病模型
IF 12.8 1区 工程技术 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2024-07-01 Epub Date: 2024-06-20 DOI: 10.1146/annurev-bioeng-072623-044010
Samira Musah, Rohan Bhattacharya, Jonathan Himmelfarb

Kidney disease is a global health crisis affecting more than 850 million people worldwide. In the United States, annual Medicare expenditures for kidney disease and organ failure exceed $81 billion. Efforts to develop targeted therapeutics are limited by a poor understanding of the molecular mechanisms underlying human kidney disease onset and progression. Additionally, 90% of drug candidates fail in human clinical trials, often due to toxicity and efficacy not accurately predicted in animal models. The advent of ex vivo kidney models, such as those engineered from induced pluripotent stem (iPS) cells and organ-on-a-chip (organ-chip) systems, has garnered considerable interest owing to their ability to more accurately model tissue development and patient-specific responses and drug toxicity. This review describes recent advances in developing kidney organoids and organ-chips by harnessing iPS cell biology to model human-specific kidney functions and disease states. We also discuss challenges that must be overcome to realize the potential of organoids and organ-chips as dynamic and functional conduits of the human kidney. Achieving these technological advances could revolutionize personalized medicine applications and therapeutic discovery for kidney disease.

肾病是影响全球 8.5 亿多人的全球性健康危机。在美国,每年用于肾脏疾病和器官衰竭的医疗保险支出超过 810 亿美元。由于对人类肾病发病和进展的分子机制了解甚少,开发靶向治疗药物的努力受到了限制。此外,90% 的候选药物在人体临床试验中失败,其原因往往是动物模型无法准确预测毒性和疗效。体内外肾脏模型的出现,例如由诱导多能干细胞(iPS)和器官芯片(organ-on-a-chip)系统设计的肾脏模型,因其能更准确地模拟组织发育、患者特异性反应和药物毒性而备受关注。本综述介绍了利用 iPS 细胞生物学技术开发肾脏器官组织和器官芯片以模拟人类特异性肾脏功能和疾病状态的最新进展。我们还讨论了要实现器官组织和器官芯片作为人体肾脏动态功能管道的潜力所必须克服的挑战。实现这些技术进步将彻底改变肾脏疾病的个性化医疗应用和治疗发现。生物医学工程年度综述》第 26 卷的最终在线出版日期预计为 2024 年 5 月。修订后的预计日期请参见 http://www.annualreviews.org/page/journal/pubdates。
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引用次数: 0
Recent Developments in Aerosol Pulmonary Drug Delivery: New Technologies, New Cargos, and New Targets. 肺部气溶胶给药的最新发展:新技术、新载体和新目标。
IF 12.8 1区 工程技术 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2024-07-01 Epub Date: 2024-06-20 DOI: 10.1146/annurev-bioeng-110122-010848
Ian R Woodward, Catherine A Fromen

There is nothing like a global pandemic to motivate the need for improved respiratory treatments and mucosal vaccines. Stimulated by the COVID-19 pandemic, pulmonary aerosol drug delivery has seen a flourish of activity, building on the prior decades of innovation in particle engineering, inhaler device technologies, and clinical understanding. As such, the field has expanded into new directions and is working toward the efficient delivery of increasingly complex cargos to address a wider range of respiratory diseases. This review seeks to highlight recent innovations in approaches to personalize inhalation drug delivery, deliver complex cargos, and diversify the targets treated and prevented through pulmonary drug delivery. We aim to inform readers of the emerging efforts within the field and predict where future breakthroughs are expected to impact the treatment of respiratory diseases.

没有什么比全球性大流行更能激发人们对改进呼吸道治疗和粘膜疫苗的需求了。在 COVID-19 大流行的刺激下,肺部气溶胶给药技术在过去几十年的粒子工程、吸入器设备技术和临床认识创新的基础上蓬勃发展。因此,该领域已扩展到新的方向,并致力于高效输送日益复杂的载体,以应对更广泛的呼吸系统疾病。本综述旨在重点介绍在个性化吸入给药、给药复杂载体以及通过肺部给药治疗和预防靶点多样化等方面的最新创新方法。我们旨在向读者介绍该领域新出现的努力,并预测未来的突破有望在哪些方面影响呼吸系统疾病的治疗。生物医学工程年度评论》第 26 卷的最终在线出版日期预计为 2024 年 5 月。修订后的预计日期请参见 http://www.annualreviews.org/page/journal/pubdates。
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引用次数: 0
Electronic Skin: Opportunities and Challenges in Convergence with Machine Learning. 电子皮肤:与机器学习融合的机遇与挑战。
IF 12.8 1区 工程技术 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2024-07-01 DOI: 10.1146/annurev-bioeng-103122-032652
Ja Hoon Koo, Young Joong Lee, Hye Jin Kim, Wojciech Matusik, Dae-Hyeong Kim, Hyoyoung Jeong

Recent advancements in soft electronic skin (e-skin) have led to the development of human-like devices that reproduce the skin's functions and physical attributes. These devices are being explored for applications in robotic prostheses as well as for collecting biopotentials for disease diagnosis and treatment, as exemplified by biomedical e-skins. More recently, machine learning (ML) has been utilized to enhance device control accuracy and data processing efficiency. The convergence of e-skin technologies with ML is promoting their translation into clinical practice, especially in healthcare. This review highlights the latest developments in ML-reinforced e-skin devices for robotic prostheses and biomedical instrumentations. We first describe technological breakthroughs in state-of-the-art e-skin devices, emphasizing technologies that achieve skin-like properties. We then introduce ML methods adopted for control optimization and pattern recognition, followed by practical applications that converge the two technologies. Lastly, we briefly discuss the challenges this interdisciplinary research encounters in its clinical and industrial transition.

软电子皮肤(e-skin)领域的最新进展促使人们开发出能够再现皮肤功能和物理属性的类人设备。人们正在探索将这些设备应用于机器人假肢,以及收集生物电位用于疾病诊断和治疗,生物医学电子皮肤就是一个很好的例子。最近,机器学习(ML)已被用于提高设备控制精度和数据处理效率。电子皮肤技术与 ML 的融合正在促进它们转化为临床实践,特别是在医疗保健领域。本综述重点介绍了用于机器人假肢和生物医学仪器的 ML 强化电子皮肤设备的最新发展。我们首先介绍了最先进的电子皮肤设备的技术突破,强调了实现类皮肤特性的技术。然后,我们介绍了用于控制优化和模式识别的 ML 方法,接着介绍了将这两种技术融合在一起的实际应用。最后,我们简要讨论了这一跨学科研究在临床和工业转型中遇到的挑战。
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引用次数: 0
Fly Me to the Micron: Microtechnologies for Drosophila Research. 让我飞向微米:果蝇研究的微技术》。
IF 12.8 1区 工程技术 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2024-07-01 DOI: 10.1146/annurev-bioeng-050423-054647
Utku M Sonmez, Nolan Frey, Philip R LeDuc, Jonathan S Minden

Multicellular model organisms, such as Drosophila melanogaster (fruit fly), are frequently used in a myriad of biological research studies due to their biological significance and global standardization. However, traditional tools used in these studies generally require manual handling, subjective phenotyping, and bulk treatment of the organisms, resulting in laborious experimental protocols with limited accuracy. Advancements in microtechnology over the course of the last two decades have allowed researchers to develop automated, high-throughput, and multifunctional experimental tools that enable novel experimental paradigms that would not be possible otherwise. We discuss recent advances in microtechnological systems developed for small model organisms using D. melanogaster as an example. We critically analyze the state of the field by comparing the systems produced for different applications. Additionally, we suggest design guidelines, operational tips, and new research directions based on the technical and knowledge gaps in the literature. This review aims to foster interdisciplinary work by helping engineers to familiarize themselves with model organisms while presenting the most recent advances in microengineering strategies to biologists.

多细胞模式生物(如黑腹果蝇)因其生物学意义和全球标准化而经常被用于各种生物学研究。然而,这些研究中使用的传统工具通常需要人工处理、主观表型和对生物体进行大量处理,导致实验方案费力且准确性有限。在过去二十年里,微型技术的进步使研究人员能够开发出自动化、高通量和多功能的实验工具,从而实现了新颖的实验范例,而这在其他情况下是不可能实现的。我们以黑腹蝇蛆为例,讨论了为小型模式生物开发的微型技术系统的最新进展。通过比较为不同应用开发的系统,我们对该领域的现状进行了批判性分析。此外,我们还根据文献中的技术和知识空白,提出了设计指南、操作提示和新的研究方向。本综述旨在帮助工程师熟悉模式生物,同时向生物学家介绍微工程策略的最新进展,从而促进跨学科工作。
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引用次数: 0
3D Traction Force Microscopy in Biological Gels: From Single Cells to Multicellular Spheroids. 生物凝胶中的三维牵引力显微镜:从单细胞到多细胞球。
IF 12.8 1区 工程技术 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2024-07-01 Epub Date: 2024-06-20 DOI: 10.1146/annurev-bioeng-103122-031130
Brian C H Cheung, Rana J Abbed, Mingming Wu, Susan E Leggett

Cell traction force plays a critical role in directing cellular functions, such as proliferation, migration, and differentiation. Current understanding of cell traction force is largely derived from 2D measurements where cells are plated on 2D substrates. However, 2D measurements do not recapitulate a vital aspect of living systems; that is, cells actively remodel their surrounding extracellular matrix (ECM), and the remodeled ECM, in return, can have a profound impact on cell phenotype and traction force generation. This reciprocal adaptivity of living systems is encoded in the material properties of biological gels. In this review, we summarize recent progress in measuring cell traction force for cells embedded within 3D biological gels, with an emphasis on cell-ECM cross talk. We also provide perspectives on tools and techniques that could be adapted to measure cell traction force in complex biochemical and biophysical environments.

细胞牵引力在引导细胞功能(如增殖、迁移和分化)方面起着至关重要的作用。目前对细胞牵引力的了解主要来自二维测量,即把细胞培养在二维基底上。然而,二维测量并不能再现生命系统的一个重要方面,即细胞会主动重塑其周围的细胞外基质(ECM),而重塑后的 ECM 又会对细胞表型和牵引力的产生产生深远的影响。生物系统的这种相互适应性体现在生物凝胶的材料特性中。在这篇综述中,我们总结了最近在测量嵌入三维生物凝胶中的细胞牵引力方面取得的进展,重点是细胞-ECM 交叉对话。我们还对可用于测量复杂生化和生物物理环境中细胞牵引力的工具和技术进行了展望。生物医学工程年度综述》第 26 卷的最终在线出版日期预计为 2024 年 5 月。修订后的预计日期请参见 http://www.annualreviews.org/page/journal/pubdates。
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引用次数: 0
Medical Microrobots 医疗微型机器人
IF 9.7 1区 工程技术 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2024-04-10 DOI: 10.1146/annurev-bioeng-081523-033131
Veronica Iacovacci, Eric Diller, Daniel Ahmed, Arianna Menciassi
Scientists around the world have long aimed to produce miniature robots that can be controlled inside the human body to aid doctors in identifying and treating diseases. Such microrobots hold the potential to access hard-to-reach areas of the body through the natural lumina. Wireless access has the potential to overcome drawbacks of systemic therapy, as well as to enable completely new minimally invasive procedures. The aim of this review is fourfold: first, to provide a collection of valuable anatomical and physiological information on the target working environments together with engineering tools for the design of medical microrobots; second, to provide a comprehensive updated survey of the technological state of the art in relevant classes of medical microrobots; third, to analyze currently available tracking and closed loop control strategies compatible with the in-body environment; and fourth, to explore the challenges still in place, to steer and inspire future research.
长期以来,世界各地的科学家一直致力于制造可在人体内控制的微型机器人,以帮助医生识别和治疗疾病。这种微型机器人有可能通过自然腔道进入人体难以到达的部位。无线接入有可能克服系统疗法的缺点,并实现全新的微创手术。本综述的目的有四个方面:第一,收集有关目标工作环境的宝贵解剖学和生理学信息,以及设计医疗微型机器人的工程工具;第二,全面介绍相关类别医疗微型机器人的最新技术状况;第三,分析目前可用的与体内环境兼容的跟踪和闭环控制策略;第四,探讨仍然存在的挑战,以指导和启发未来的研究。
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引用次数: 0
Patient-Specific, Mechanistic Models of Tumor Growth Incorporating Artificial Intelligence and Big Data 结合人工智能和大数据的肿瘤生长患者特异性机制模型
IF 9.7 1区 工程技术 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2024-04-10 DOI: 10.1146/annurev-bioeng-081623-025834
Guillermo Lorenzo, Syed Rakin Ahmed, David A. Hormuth II, Brenna Vaughn, Jayashree Kalpathy-Cramer, Luis Solorio, Thomas E. Yankeelov, Hector Gomez
Despite the remarkable advances in cancer diagnosis, treatment, and management over the past decade, malignant tumors remain a major public health problem. Further progress in combating cancer may be enabled by personalizing the delivery of therapies according to the predicted response for each individual patient. The design of personalized therapies requires the integration of patient-specific information with an appropriate mathematical model of tumor response. A fundamental barrier to realizing this paradigm is the current lack of a rigorous yet practical mathematical theory of tumor initiation, development, invasion, and response to therapy. We begin this review with an overview of different approaches to modeling tumor growth and treatment, including mechanistic as well as data-driven models based on big data and artificial intelligence. We then present illustrative examples of mathematical models manifesting their utility and discuss the limitations of stand-alone mechanistic and data-driven models. We then discuss the potential of mechanistic models for not only predicting but also optimizing response to therapy on a patient-specific basis. We describe current efforts and future possibilities to integrate mechanistic and data-driven models. We conclude by proposing five fundamental challenges that must be addressed to fully realize personalized care for cancer patients driven by computational models.
尽管过去十年来癌症诊断、治疗和管理取得了长足的进步,但恶性肿瘤仍然是一个重大的公共卫生问题。根据每个患者的预测反应提供个性化疗法,可在抗击癌症方面取得进一步进展。个性化疗法的设计需要将患者的特定信息与适当的肿瘤反应数学模型相结合。实现这一模式的根本障碍是目前缺乏关于肿瘤发生、发展、侵袭和治疗反应的严谨而实用的数学理论。本综述首先概述了肿瘤生长和治疗建模的不同方法,包括机理模型以及基于大数据和人工智能的数据驱动模型。然后,我们将举例说明数学模型的实用性,并讨论独立机理模型和数据驱动模型的局限性。然后,我们讨论了机理模型在预测和优化特定患者治疗反应方面的潜力。我们介绍了整合机理模型和数据驱动模型的当前努力和未来可能性。最后,我们提出了五个必须解决的基本挑战,以充分实现由计算模型驱动的癌症患者个性化治疗。
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引用次数: 0
Integrating Upper-Limb Prostheses with the Human Body: Technology Advances, Readiness, and Roles in Human–Prosthesis Interaction 上肢假肢与人体的结合:技术进步、准备情况以及在人与假肢互动中的作用
IF 9.7 1区 工程技术 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2024-04-10 DOI: 10.1146/annurev-bioeng-110222-095816
He (Helen) Huang, Levi J. Hargrove, Max Ortiz-Catalan, Jonathon W. Sensinger
Significant advances in bionic prosthetics have occurred in the past two decades. The field's rapid expansion has yielded many exciting technologies that can enhance the physical, functional, and cognitive integration of a prosthetic limb with a human. We review advances in the engineering of prosthetic devices and their interfaces with the human nervous system, as well as various surgical techniques for altering human neuromusculoskeletal systems for seamless human–prosthesis integration. We discuss significant advancements in research and clinical translation, focusing on upper limb prosthetics since they heavily rely on user intent for daily operation, although many discussed technologies have been extended to lower limb prostheses as well. In addition, our review emphasizes the roles of advanced prosthetics technologies in complex interactions with humans and the technology readiness levels (TRLs) of individual research advances. Finally, we discuss current gaps and controversies in the field and point out future research directions, guided by TRLs.
过去二十年来,仿生假肢技术取得了长足的进步。该领域的快速发展产生了许多令人兴奋的技术,这些技术可以增强假肢与人体在物理、功能和认知方面的融合。我们回顾了假肢装置工程学及其与人体神经系统接口方面的进展,以及改变人体神经-肌肉-骨骼系统以实现人体-假肢无缝整合的各种外科技术。我们将重点讨论上肢假肢在研究和临床转化方面取得的重大进展,因为上肢假肢的日常操作严重依赖于使用者的意图,尽管所讨论的许多技术也已扩展到下肢假肢。此外,我们的综述还强调了先进假肢技术在与人类复杂互动中的作用,以及各项研究进展的技术就绪水平(TRL)。最后,我们讨论了该领域目前存在的差距和争议,并在 TRLs 的指导下指出了未来的研究方向。
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引用次数: 0
Plasmonic-Driven Regulation of Biomolecular Activity In Situ 等离子体驱动的生物分子活性原位调控
IF 9.7 1区 工程技术 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2024-04-10 DOI: 10.1146/annurev-bioeng-110222-105043
Chen Xie, Tingting Zhang, Zhenpeng Qin
Selective and remote manipulation of activity for biomolecules, including protein, DNA, and lipids, is crucial to elucidate the molecular function and to develop biomedical applications. While advances in tool development, such as optogenetics, have significantly impacted these directions, the requirement for genetic modification significantly limits their therapeutic applications. Plasmonic nanoparticle heating has brought new opportunities to the field, as hot nanoparticles are unique point heat sources at the nanoscale. In this review, we summarize fundamental engineering problems such as plasmonic heating and the resulting biomolecular responses. We highlight the biological responses and applications of manipulating biomolecules and provide perspectives for future directions in the field.
选择性和远程操纵生物大分子(包括蛋白质、DNA 和脂质)的活性对于阐明分子功能和开发生物医学应用至关重要。虽然光遗传学等工具开发的进步对这些方向产生了重大影响,但基因修饰的要求极大地限制了其治疗应用。质子纳米粒子加热为该领域带来了新的机遇,因为热纳米粒子是纳米尺度上独特的点热源。在这篇综述中,我们总结了质子加热等基础工程问题以及由此产生的生物分子反应。我们强调了操纵生物分子的生物反应和应用,并为该领域的未来发展方向提供了展望。
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引用次数: 0
Predictive Models for Health Deterioration: Understanding Disease Pathways for Personalized Medicine. 健康恶化的预测模型:了解个性化医疗的疾病途径。
IF 9.7 1区 工程技术 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2023-06-08 Epub Date: 2023-02-28 DOI: 10.1146/annurev-bioeng-110220-030247
Bjoern M Eskofier, Jochen Klucken

Artificial intelligence (AI) and machine learning (ML) methods are currently widely employed in medicine and healthcare. A PubMed search returns more than 100,000 articles on these topics published between 2018 and 2022 alone. Notwithstanding several recent reviews in various subfields of AI and ML in medicine, we have yet to see a comprehensive review around the methods' use in longitudinal analysis and prediction of an individual patient's health status within a personalized disease pathway. This review seeks to fill that gap. After an overview of the AI and ML methods employed in this field and of specific medical applications of models of this type, the review discusses the strengths and limitations of current studies and looks ahead to future strands of research in this field. We aim to enable interested readers to gain a detailed impression of the research currently available and accordingly plan future work around predictive models for deterioration in health status.

人工智能(AI)和机器学习(ML)方法目前广泛应用于医学和医疗保健领域。PubMed搜索结果显示,仅在2018年至2022年期间,就有超过10万篇关于这些主题的文章发表。尽管最近对医学中人工智能和机器学习的各个子领域进行了一些综述,但我们还没有看到关于这些方法在个性化疾病途径中用于纵向分析和预测个体患者健康状况的全面综述。本文旨在填补这一空白。在概述了该领域使用的人工智能和机器学习方法以及该类型模型的具体医学应用之后,本文讨论了当前研究的优势和局限性,并展望了该领域未来的研究方向。我们的目标是使有兴趣的读者获得目前可用的研究的详细印象,并相应地围绕健康状况恶化的预测模型计划未来的工作。
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引用次数: 0
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Annual Review of Biomedical Engineering
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