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Preclinical Models of Metabolic Dysfunction-Associated Steatotic Liver Disease for Therapeutic Testing. 代谢功能障碍相关脂肪变性肝病治疗试验的临床前模型
IF 9.6 1区 工程技术 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2026-02-05 DOI: 10.1146/annurev-bioeng-081325-053420
Alissa M Cutrone, Heidi Yeh, Korkut Uygun, O Berk Usta

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent hepatic pathology worldwide, with significant potential for progression to cirrhosis and ultimately end-stage liver disease. Accordingly, a wide range of preclinical models have been developed to better understand the disease mechanisms and progression as well as to accelerate drug discovery. These include in vitro, ex vivo, and in vivo models, which offer unique advantages yet differ in terms of disease driver, species used, and biological complexity-ranging from benchtop cellular systems to whole organs and organisms. In this review, we provide a comprehensive overview of the technologies currently used for the study of MASLD, with a focus on how standardization of disease progression across models may aid therapeutic development.

代谢功能障碍相关脂肪变性肝病(MASLD)是世界范围内最常见的肝脏病理,具有发展为肝硬化和最终终末期肝病的巨大潜力。因此,广泛的临床前模型已经被开发出来,以更好地了解疾病的机制和进展,并加速药物的发现。这些模型包括体外、离体和体内模型,它们具有独特的优势,但在疾病驱动因素、使用的物种和生物复杂性方面存在差异——从台式细胞系统到整个器官和生物体。在这篇综述中,我们对目前用于MASLD研究的技术进行了全面的概述,重点是跨模型的疾病进展标准化如何有助于治疗开发。
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引用次数: 0
Type 1 Diabetes and Islet Encapsulation: From Historical Milestones to Cutting-Edge Advances. 1型糖尿病和胰岛封装:从历史里程碑到前沿进展。
IF 9.6 1区 工程技术 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2026-01-29 DOI: 10.1146/annurev-bioeng-110824-024435
Sudip Mukherjee, Snehasish Mandal, José Oberholzer, Omid Veiseh

Type 1 diabetes (T1D) is a chronic condition in which patients suffer from high blood glucose levels due to the body's inability to produce sufficient insulin. Continuous insulin administration and T1D management are difficult, often leading to hypoglycemic events, insulin resistance, and lower quality of life. Major advancements have been made in recent years, including clinical islet transplantation, but their application is limited by rapid immune rejection and islet destruction. Thus, a necessary paradigm shift has been observed in recent times toward biomaterial-based islet transplantation therapy. The use of biomaterial-based encapsulation addresses major limitations, including immune rejection and hypoxia, and provides a proper cell microenvironment offering greater islet viability. Presently, researchers are more focused on developing a clinically translatable therapy for T1D with the existing knowledge of advanced biomaterial technology. In this review article, we provide a historical perspective, highlighting the developments in the field of islet encapsulation and transplantation, and focus on cutting-edge advancements with modern bioengineering from a clinical perspective.

1型糖尿病(T1D)是一种慢性疾病,患者由于身体无法产生足够的胰岛素而患有高血糖水平。持续胰岛素治疗和T1D治疗是困难的,经常导致低血糖事件、胰岛素抵抗和生活质量下降。近年来取得了重大进展,包括临床胰岛移植,但其应用受到快速免疫排斥和胰岛破坏的限制。因此,近年来观察到以生物材料为基础的胰岛移植治疗发生了必要的范式转变。使用基于生物材料的包封解决了主要的局限性,包括免疫排斥和缺氧,并提供了一个适当的细胞微环境,提供了更大的胰岛活力。目前,研究人员更关注的是利用先进的生物材料技术知识,开发临床可翻译的T1D治疗方法。在这篇综述文章中,我们提供了一个历史的角度,重点介绍了胰岛包封和移植领域的发展,并从临床的角度关注现代生物工程的前沿进展。
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引用次数: 0
Radiomics++: Review of Habitat Imaging Analysis for Decoding Tumor Heterogeneity. 放射组学++:生境成像分析解码肿瘤异质性的综述。
IF 9.6 1区 工程技术 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2026-01-27 DOI: 10.1146/annurev-bioeng-031825-040442
Jiaojiao Wu, Yuwei Xia, Xuechun Wang, Feng Shi, Dinggang Shen

Tumors display genomic and phenotypic heterogeneity, which holds prognostic significance and may influence therapy response. Radiographic imaging modalities, such as computed tomography, magnetic resonance imaging, nuclear medicine techniques, and ultrasonography, are routinely used to generate parametric maps to identify, measure, and map tumor heterogeneity from different perspectives encompassing anatomy, physiology, and metabolism. This review underscores the potential of artificial intelligence (AI)-based habitat imaging analysis, referred to as Radiomics++, in decoding intratumor heterogeneity compared to conventional radiomics. We highlight the general workflow, underlying principles, detailed methodology, and clinical applications of habitat imaging analysis to guide researchers. Validation advancements are then reviewed to verify the reliability of generated habitats by correlating radiologic phenotypes with biologic underpinnings. Furthermore, we address key challenges and opportunities in clinical translation, including data heterogeneity, model performance, and interpretability. Finally, integrating AI-defined habitats with multi-omics is anticipated to deepen our understanding of tumor evolution and advance precision medicine.

肿瘤表现出基因组和表型异质性,这具有预后意义并可能影响治疗反应。放射成像方式,如计算机断层扫描、磁共振成像、核医学技术和超声检查,通常用于生成参数图,从解剖学、生理学和代谢的不同角度识别、测量和绘制肿瘤异质性。这篇综述强调了与传统放射组学相比,基于人工智能(AI)的栖息地成像分析(称为Radiomics++)在解码肿瘤内异质性方面的潜力。我们重点介绍了栖息地成像分析的一般工作流程、基本原理、详细方法和临床应用,以指导研究人员。然后回顾验证进展,通过将放射学表型与生物学基础相关联来验证生成栖息地的可靠性。此外,我们还讨论了临床翻译中的关键挑战和机遇,包括数据异质性、模型性能和可解释性。最后,将人工智能定义的栖息地与多组学相结合,有望加深我们对肿瘤进化的理解,推动精准医学的发展。
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引用次数: 0
Multimodal Toxicity of Acrolein and Associated Therapeutic Strategies in Central Nervous System Trauma and Disease. 丙烯醛在中枢神经系统创伤和疾病中的多模态毒性及相关治疗策略。
IF 9.6 1区 工程技术 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2026-01-21 DOI: 10.1146/annurev-bioeng-103023-035352
Nicholas S Race, Koji Uchida, Philip C Burcham, Riyi Shi

Acrolein is a highly reactive α,β-unsaturated aldehyde produced endogenously through lipid peroxidation and enzymatic metabolism and exogenously via environmental exposures. Acrolein covalently adducts to DNA and proteins, leading to oxidative stress, mitochondrial dysfunction, and inflammation, including innate immune response activation via natural antibodies. Acrolein is difficult to measure in biological systems, but acrolein-bound covalent products can be measured reliably. Therapeutically, nucleophilic small molecules that scavenge acrolein such as hydralazine, phenelzine, dimercaprol, carnosine, and N-acetylcysteine (NAC) have shown neuroprotective effects in animal models of multiple sclerosis, Parkinson's disease, spinal cord injury, and traumatic brain injury. These effects include preserved membrane and mitochondrial integrity, reduced inflammation, reduced pain, and improved motor, sensory, and cognitive outcomes. Alternative strategies that enhance clearance or inhibit production of acrolein show promise but face limitations. Acrolein is a key pathophysiological mediator and a viable therapeutic target in central nervous system trauma and neurodegenerative diseases.

丙烯醛是一种高活性的α,β-不饱和醛,内源性通过脂质过氧化和酶代谢产生,外源性通过环境暴露产生。丙烯醛共价加合DNA和蛋白质,导致氧化应激、线粒体功能障碍和炎症,包括通过天然抗体激活先天免疫反应。丙烯醛在生物体系中很难测量,但丙烯醛结合共价产物可以可靠地测量。在治疗方面,清除丙烯醛的亲核小分子,如肼、苯乙嗪、二巯基醇、肌肽和n -乙酰半胱氨酸(NAC),在多发性硬化症、帕金森病、脊髓损伤和创伤性脑损伤的动物模型中显示出神经保护作用。这些影响包括保持膜和线粒体的完整性,减少炎症,减轻疼痛,改善运动,感觉和认知结果。增强清除或抑制丙烯醛生产的替代策略显示出希望,但面临局限性。丙烯醛是中枢神经系统损伤和神经退行性疾病的重要病理生理介质和可行的治疗靶点。
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引用次数: 0
Federated Learning in Healthcare: From Research to Real-World Deployment. 医疗保健中的联邦学习:从研究到实际部署。
IF 9.6 1区 工程技术 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2026-01-21 DOI: 10.1146/annurev-bioeng-080125-041414
Spyridon Bakas, Xiaoxiao Li, Prashant Shah, Holger R Roth

Artificial intelligence (AI), including deep and traditional machine learning, holds great promise for advancing biomedical research and healthcare. However, most AI studies remain academic in nature and rarely transition into clinical practice, largely due to limited access to diverse real-world datasets. Centralized learning, the traditional approach to multi-institutional collaboration, is hindered by privacy, legal, and logistical barriers. Federated learning (FL) offers a decentralized alternative, enabling institutions to collaboratively train models without sharing sensitive patient data. This article reviews key algorithmic, privacy, and practical developments in FL for biomedical engineering, including strategies to handle non-identical data distributions and safeguard privacy through differential privacy, secure aggregation, and confidential computing. We also discuss current limitations and considerations for the need of scalable, interoperable infrastructures. FL represents a paradigm shift toward building generalizable, equitable, and clinically impactful AI models. Realizing this vision requires continued advances, such as FL-as-a-service platforms and regulatory-aligned workflows that support persistent and trustworthy model deployment to truly realize AI's promise in patient care.

人工智能(AI),包括深度和传统的机器学习,在推进生物医学研究和医疗保健方面有着巨大的希望。然而,大多数人工智能研究仍然是学术性的,很少过渡到临床实践,这主要是由于对各种现实世界数据集的访问有限。集中式学习是多机构协作的传统方法,受到隐私、法律和后勤障碍的阻碍。联邦学习(FL)提供了一种分散的替代方案,使机构能够在不共享敏感患者数据的情况下协作训练模型。本文回顾了用于生物医学工程的FL的关键算法、隐私和实际发展,包括处理非相同数据分布和通过差异隐私、安全聚合和机密计算保护隐私的策略。我们还讨论了当前对可伸缩、可互操作的基础设施需求的限制和考虑。FL代表了向建立可推广、公平和临床有效的人工智能模型的范式转变。实现这一愿景需要持续的进步,例如fl即服务平台和与监管相一致的工作流程,这些工作流程支持持续且值得信赖的模型部署,以真正实现人工智能在患者护理中的承诺。
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引用次数: 0
Opportunities and Challenges in Precision Neurotherapeutics. 精准神经治疗的机遇与挑战。
IF 9.6 1区 工程技术 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2026-01-16 DOI: 10.1146/annurev-bioeng-110824-031709
Lilianne R Mujica-Parodi, Dost Öngür, R Mark Richardson

Precision neurotherapeutics represents a transformative paradigm shift from standardized "one-size-fits-all" treatments of neurological, neurodegenerative, and/or psychiatric disorders toward individualized interventions that leverage patient-specific biological, behavioral, and physiological characteristics. Traditional neurotherapeutic approaches achieve modest response rates of 30-60% for first-line treatments, necessitating personalized strategies that account for individual differences in genetics, brain structure and function, and treatment response profiles. This review examines advances across three core domains: pharmaceutical approaches utilizing fragment-based drug discovery, pharmacokinetic modeling, and quantitative systems pharmacology; neuromodulation technologies evolving from open-loop to adaptive closed-loop systems with real-time biomarker feedback; and biomarker development spanning neuroimaging, pharmacogenomics, and digital health applications. Critical challenges include developing robust methodological frameworks for single-subject parameter estimation, addressing signal-to-noise ratio limitations in neuroimaging, and navigating complex regulatory landscapes. The convergence of artificial intelligence, computational modeling, and US Food and Drug Administration policy shifts toward in silico approaches creates unprecedented opportunities for mechanistically informed biomarkers that can guide truly personalized mental health care.

精确神经治疗代表了一种革命性的范式转变,从标准化的“一刀切”的神经、神经退行性疾病和/或精神疾病治疗,转向利用患者特定的生物、行为和生理特征的个性化干预。传统的神经治疗方法在一线治疗中达到30-60%的适度反应率,需要个性化的策略,考虑到遗传、大脑结构和功能以及治疗反应概况的个体差异。本文综述了三个核心领域的进展:利用基于片段的药物发现、药代动力学建模和定量系统药理学的药物方法;生物标志物实时反馈的神经调节技术从开环向自适应闭环进化生物标志物开发跨越神经成像、药物基因组学和数字健康应用。关键的挑战包括为单受试者参数估计开发强大的方法框架,解决神经成像中的信噪比限制,以及导航复杂的监管景观。人工智能、计算建模和美国食品和药物管理局(fda)政策转向计算机方法的融合,为机械信息生物标志物创造了前所未有的机会,这些生物标志物可以指导真正个性化的精神卫生保健。
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引用次数: 0
Silicon Photonic Biosensors in Clinical Diagnostics: Emerging Opportunities and Challenges. 硅光子生物传感器在临床诊断:新兴的机遇和挑战。
IF 9.6 1区 工程技术 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2026-01-13 DOI: 10.1146/annurev-bioeng-103023-030143
Patricia Ramirez-Priego, Andrés Alonso-Fernández, Maria Soler, Laura M Lechuga

As health care systems worldwide seek to decentralize diagnostics and expand precision medicine, silicon photonic biosensors have become a compelling solution. Their development over the past decade, especially in the last 5 years, marks a significant convergence of photonics, nanotechnology, and biomedical engineering that aims to reshape the diagnostic landscape. This review presents a comprehensive analysis of advances in silicon photonic biosensors, focusing on key configurations including microring resonators, photonic crystals, interferometers, and other emerging transduction mechanisms. We discuss the integration of advanced surface functionalization strategies for efficient and robust bioreceptor immobilization, which is critical for reliable biomedical applications. We emphasize the translation of these devices into clinical settings, primarily in infectious diseases and cancer diagnostics. Finally, we address current limitations, such as fabrication complexity, microfluidic integration, and data interpretation, and outline future directions to enhance scalability and clinical adoption in personalized medicine and decentralized health care.

随着全球医疗保健系统寻求分散诊断和扩展精确医疗,硅光子生物传感器已成为一种引人注目的解决方案。它们在过去十年,特别是过去五年的发展,标志着光子学、纳米技术和生物医学工程的重大融合,旨在重塑诊断领域。本文综述了硅光子生物传感器的进展,重点介绍了微环谐振器、光子晶体、干涉仪和其他新兴的转导机制等关键配置。我们讨论了先进的表面功能化策略的整合,以实现高效和稳健的生物受体固定化,这对于可靠的生物医学应用至关重要。我们强调这些设备的翻译到临床设置,主要是在传染病和癌症诊断。最后,我们解决了当前的局限性,如制造复杂性,微流控集成和数据解释,并概述了未来的方向,以提高个性化医疗和分散医疗的可扩展性和临床采用。
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引用次数: 0
A Holistic and Dynamic Network-Level View of the Autonomic Nervous System. 自主神经系统的整体和动态网络水平观点。
IF 9.6 1区 工程技术 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2025-12-19 DOI: 10.1146/annurev-bioeng-103023-065411
Sandya Subramanian, Zhe Sage Chen, Riccardo Barbieri, Sriram Gadepalli

The autonomic nervous system (ANS) plays a vital role in health care for both acute care and chronic diseases. The traditional view of the ANS is to divide it into individual organ systems and study the separate components with a reductionist approach, which has been proven insufficient. Here, we argue that a holistic network-level view of the ANS is critical for generating new insights and deepening our understanding of its complex and dynamic functions. In this review, we treat the ANS as such a coordinated and dynamic network. We advocate for studying its interactions with major organ systems and the central nervous system using continuous and longitudinal monitoring in ambulatory and at-home settings rather than clinic-based snapshots. We first briefly review ANS physiology, then outline our network perspective, and finally highlight cutting-edge research directions and emerging engineering innovations in ANS monitoring, modeling, and modulation that benefit from this network-level view.

自主神经系统(ANS)在急性和慢性疾病的医疗保健中起着至关重要的作用。ANS的传统观点是将其划分为单个的器官系统,并以还原论的方法研究其单独的组成部分,这已被证明是不够的。在这里,我们认为,对ANS的整体网络级视图对于产生新的见解和加深我们对其复杂和动态功能的理解至关重要。在这篇综述中,我们将ANS视为这样一个协调和动态的网络。我们提倡研究其与主要器官系统和中枢神经系统的相互作用,在门诊和家庭环境中使用连续和纵向监测,而不是基于临床的快照。我们首先简要回顾了ANS生理学,然后概述了我们的网络视角,最后重点介绍了得益于这种网络层面观点的ANS监测、建模和调制的前沿研究方向和新兴工程创新。
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引用次数: 0
Supracortical Microstimulation: Advances in Microelectrode Design and In Vivo Validation. 超实用微刺激:微电极设计和体内验证的进展。
IF 9.6 1区 工程技术 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2025-05-01 Epub Date: 2025-02-06 DOI: 10.1146/annurev-bioeng-103023-072855
Cecilia Schmitz, J Evan Smith, Iakov Rachinskiy, Bijan Pesaran, Flavia Vitale, Marc Sommer, Jonathan Viventi

Electrical stimulation of the brain is being developed as a treatment for an increasing number of neurological disorders. Technologies for delivering electrical stimulation are advancing rapidly and vary in specificity, coverage, and invasiveness. Supracortical microstimulation (SCMS), characterized by microelectrode contacts placed on the epidural or subdural cortical surface, achieves a balance between the advantages and limitations of other electrical stimulation technologies by delivering spatially precise activation without disrupting the integrity of the cortex. However, in vivo experiments involving SCMS have not been comprehensively summarized. Here, we review the field of SCMS, focusing on recent advances, to guide the development of clinically translatable supracortical microelectrodes. We also highlight the gaps in our understanding of the biophysical effects of this technology. Future work investigating the unique electrochemical properties of supracortical microelectrodes and validating SCMS in nonhuman primate preclinical studies can enable rapid clinical translation of innovative treatments for humans with neurological disorders.

脑电刺激作为一种治疗越来越多的神经系统疾病的方法正在得到发展。提供电刺激的技术正在迅速发展,在特异性、覆盖范围和侵入性方面各不相同。实践上微刺激(SCMS)的特点是在硬膜外或硬膜下皮层表面放置微电极接触,通过提供空间精确的激活而不破坏皮层的完整性,在其他电刺激技术的优点和局限性之间取得了平衡。然而,涉及SCMS的体内实验尚未得到全面总结。在这里,我们回顾了SCMS领域的最新进展,以指导临床可翻译的实践性上微电极的发展。我们还强调了我们对这项技术的生物物理效应的理解上的差距。未来研究超皮层微电极独特的电化学特性,并在非人类灵长类动物临床前研究中验证SCMS,可以使神经系统疾病患者的创新治疗方法快速临床转化。
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引用次数: 0
Human Organoids as an Emerging Tool for Genome Screenings. 人类类器官作为基因组筛选的新兴工具。
IF 9.6 1区 工程技术 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2025-05-01 DOI: 10.1146/annurev-bioeng-103023-122327
Francesco Andreatta, Delilah Hendriks, Benedetta Artegiani

Over the last decade, a plethora of organoid models have been generated to recapitulate aspects of human development, disease, tissue homeostasis, and repair. Organoids representing multiple tissues have emerged and are typically categorized based on their origin. Tissue-derived organoids are established directly from tissue-resident stem/progenitor cells of either adult or fetal origin. Starting from pluripotent stem cells (PSCs), PSC-derived organoids instead recapitulate the developmental trajectory of a given organ. Gene editing technologies, particularly the CRISPR-Cas toolbox, have greatly facilitated gene manipulation experiments with considerable ease and scalability, revolutionizing organoid-based human biology research. Here, we review the recent adaptation of CRISPR-based screenings in organoids. We examine the strategies adopted to perform CRISPR screenings in organoids, discuss different screening scopes and readouts, and highlight organoid-specific challenges. We then discuss individual organoid-based genome screening studies that have uncovered novel genes involved in a variety of biological processes. We close by providing an outlook on how widespread adaptation of CRISPR screenings across the organoid field may be achieved, to ultimately leverage our understanding of human biology.

在过去的十年中,已经产生了大量的类器官模型来概括人类发育,疾病,组织稳态和修复的各个方面。代表多种组织的类器官已经出现,通常根据它们的来源进行分类。组织来源的类器官是直接从成人或胎儿来源的组织驻留干细胞/祖细胞中建立的。从多能干细胞(PSCs)开始,PSCs衍生的类器官再现了给定器官的发育轨迹。基因编辑技术,特别是CRISPR-Cas工具箱,极大地促进了基因操作实验的相当容易和可扩展性,彻底改变了基于类器官的人类生物学研究。在这里,我们回顾了最近在类器官中基于crispr筛选的适应性。我们研究了在类器官中进行CRISPR筛选所采用的策略,讨论了不同的筛选范围和读数,并强调了类器官特异性挑战。然后,我们讨论了基于个体类器官的基因组筛选研究,这些研究发现了参与各种生物过程的新基因。最后,我们展望了CRISPR筛选在类器官领域的广泛适应性,最终利用我们对人类生物学的理解。
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引用次数: 0
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Annual Review of Biomedical Engineering
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