Ameya P. Chaudhari, Omar M. Budayr, Emily E. Bonacquisti, Caden C. Kussatz, Mark S. Bannon, Karissa J. Law, Yusha Liu, Matthew L. Bolton, Patrick M. Glassman, Leaf Huang, Juliane Nguyen
{"title":"The status of extracellular vesicles as drug carriers and therapeutics","authors":"Ameya P. Chaudhari, Omar M. Budayr, Emily E. Bonacquisti, Caden C. Kussatz, Mark S. Bannon, Karissa J. Law, Yusha Liu, Matthew L. Bolton, Patrick M. Glassman, Leaf Huang, Juliane Nguyen","doi":"10.1038/s44222-026-00405-x","DOIUrl":"10.1038/s44222-026-00405-x","url":null,"abstract":"Owing to their natural origin and biocompatibility, extracellular vesicles (EVs) are being recognized as next-generation vehicles for targeted drug delivery. Despite their potential as therapeutic carriers, EVs suffer from heterogeneity, low yields, limited cargo loading efficiency and rapid clearance by the mononuclear phagocyte system. Since the first EV-based clinical trial in 2005, more than 100 clinical trials have investigated the use of EVs as therapeutics and drug carriers. Despite this, no EV-based therapies have received regulatory approval to date. This gap between preclinical research activity and clinical translation underscores persistent scientific challenges and regulatory hurdles that continue to impede the advancement of EV-based therapeutics. In this Review, we examine the research articles published in the field between 2012 and 2024 (38,177 articles), highlighting key developments, persistent challenges and evolving assumptions. We review the current EV landscape and clinical trials, focusing on their organotropism and use as carriers for therapeutics. We compare their advantages and limitations in relation to other nanoparticles, such as lipid nanoparticles and liposomes, and examine how labelling strategies and cell sources influence EV biodistribution. Finally, we outline translational considerations for EV-based therapeutics and propose additional reporting standards, complementing the MISEV 2023 guidelines. Extracellular vesicles (EVs) are emerging as biocompatible carriers for targeted drug delivery, yet challenges in yield, cargo loading and biodistribution persist. In this Review, key trends from over a decade of research are analysed, comparing EVs with lipid-based systems and outlining strategies for improving therapeutic translation and reporting standards.","PeriodicalId":74248,"journal":{"name":"Nature reviews bioengineering","volume":"4 4","pages":"301-318"},"PeriodicalIF":37.6,"publicationDate":"2026-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147686408","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Placental organoids for drug and biomarker discovery","authors":"Claire Richards, Fatemeh Heidari, Lana McClements","doi":"10.1038/s44222-026-00409-7","DOIUrl":"10.1038/s44222-026-00409-7","url":null,"abstract":"Placental organoids offer powerful tools to advance diagnostics and therapies for pregnancy complications including preeclampsia and fetal growth restriction. However, most current models rely on animal-derived materials and heterogenous cell sources. Developing human-based physiologically relevant organoid models is essential to understand disease phenotypes and improve clinical care for high-risk pregnancies.","PeriodicalId":74248,"journal":{"name":"Nature reviews bioengineering","volume":"4 4","pages":"288-290"},"PeriodicalIF":37.6,"publicationDate":"2026-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147686404","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Artificial kinaesthesia in autonomous robotic surgery","authors":"Tangyou Liu \u0000 (, ), Sishen Yuan \u0000 (, ), Hongliang Ren \u0000 (, )","doi":"10.1038/s44222-026-00403-z","DOIUrl":"10.1038/s44222-026-00403-z","url":null,"abstract":"Surgeons depend on a finely tuned multisensory system, in which vision and kinaesthesia work in synergy to manipulate tissue with precision. Translating this to robotic systems requires a hierarchical framework of artificial kinaesthesia, progressing from physical sensing to algorithmic understanding, and finally, to synergistic control.","PeriodicalId":74248,"journal":{"name":"Nature reviews bioengineering","volume":"4 3","pages":"210-211"},"PeriodicalIF":37.6,"publicationDate":"2026-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147570390","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ester Sapir Baruch, Eric Silberman, Assaf Shapira, Tal Dvir
{"title":"Reassessing the scope and definition of 4D tissue bioprinting","authors":"Ester Sapir Baruch, Eric Silberman, Assaf Shapira, Tal Dvir","doi":"10.1038/s44222-026-00402-0","DOIUrl":"10.1038/s44222-026-00402-0","url":null,"abstract":"Four-dimensional bioprinting of tissues goes beyond cellular constructs that evolve or mature over time. It should incorporate time as an active design parameter, enabling programmed and predictable transformations. This requires implementing shape-morphing behaviour, either within materials or cell–matrix composites, to control the construct’s transition in form or size.","PeriodicalId":74248,"journal":{"name":"Nature reviews bioengineering","volume":"4 3","pages":"206-207"},"PeriodicalIF":37.6,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147570401","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Building mechanochemistry into soft biomaterials","authors":"Kristopher A. Kilian","doi":"10.1038/s44222-026-00406-w","DOIUrl":"10.1038/s44222-026-00406-w","url":null,"abstract":"When soft tissue is mechanically deformed, new material properties and functionalities can emerge. Through rational design of dynamic covalent chemistry and network architecture, new force-catalysed activities in hydrogels can be achieved, forming the basis of a ‘mechanochemical toolbox’ to expand the functionality of soft synthetic biomaterials.","PeriodicalId":74248,"journal":{"name":"Nature reviews bioengineering","volume":"4 3","pages":"208-209"},"PeriodicalIF":37.6,"publicationDate":"2026-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147570396","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Translating a bioinspired polymer into a modular surgical platform","authors":"Jeffrey Michael Karp","doi":"10.1038/s44222-026-00408-8","DOIUrl":"10.1038/s44222-026-00408-8","url":null,"abstract":"A bioresorbable, light-activated polymer, integrated with a 3D-printed chamber, enables atraumatic and sutureless peripheral nerve repair. Translating this material platform from concept to clinical reality required iterative design, scalable manufacturing, multidisciplinary collaboration and long-term vision for a versatile surgical technology.","PeriodicalId":74248,"journal":{"name":"Nature reviews bioengineering","volume":"4 4","pages":"296-297"},"PeriodicalIF":37.6,"publicationDate":"2026-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147686405","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"AI challenges science to reinvent itself","authors":"","doi":"10.1038/s44222-025-00398-z","DOIUrl":"10.1038/s44222-025-00398-z","url":null,"abstract":"As artificial intelligence enters the scientific arena, it not only compels us to rethink the scientific method but also opens the door to reimagine long-standing practices.","PeriodicalId":74248,"journal":{"name":"Nature reviews bioengineering","volume":"4 1","pages":"1-1"},"PeriodicalIF":37.6,"publicationDate":"2026-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s44222-025-00398-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145970245","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Balancing data collection and privacy protection in precision health","authors":"Seung-min Park, Hun Chung","doi":"10.1038/s44222-026-00404-y","DOIUrl":"10.1038/s44222-026-00404-y","url":null,"abstract":"Precision health is based on multimodal, personal data from individuals. However, regulatory frameworks typically require collecting only what is strictly necessary, a standard that is difficult to define in biomedicine. Here we explore how data minimization can be embedded into precision health, turning privacy from a limitation into a guiding design principle for data collection, storage and governance.","PeriodicalId":74248,"journal":{"name":"Nature reviews bioengineering","volume":"4 3","pages":"212-213"},"PeriodicalIF":37.6,"publicationDate":"2026-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147570397","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Organoid analytical toolkits","authors":"Yoonhee Jin, Seongjun Park, Seung-Woo Cho","doi":"10.1038/s44222-025-00384-5","DOIUrl":"10.1038/s44222-025-00384-5","url":null,"abstract":"3D cell culture systems such as organoids reflect the complexity of native organs more closely than traditional 2D culture systems. However, efforts to translate organoid research into clinical and industrial applications demand the development of compatible analytical platforms to accurately characterize their multifaceted physiological traits. This Review explores three vital aspects of physiological characterization — electrophysiological, biophysical and optical properties — including the role of omics and computational technologies in understanding organoid function and behaviour. Organoids offer physiologically relevant 3D models, yet translating them into clinical and industrial use requires robust analytical platforms. In this Review, key strategies for characterizing electrophysiological, biophysical and optical properties are discussed, alongside the integration of omics and computational technologies to decode organoid function and behaviour.","PeriodicalId":74248,"journal":{"name":"Nature reviews bioengineering","volume":"4 4","pages":"336-352"},"PeriodicalIF":37.6,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147686409","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zeyang Liu, Guorui Chen, Min-Seung Jo, Viola Vogel, Jun Chen, John A. Rogers, Song Li
{"title":"Mechanomedicine","authors":"Zeyang Liu, Guorui Chen, Min-Seung Jo, Viola Vogel, Jun Chen, John A. Rogers, Song Li","doi":"10.1038/s44222-025-00391-6","DOIUrl":"10.1038/s44222-025-00391-6","url":null,"abstract":"Mechanical forces act throughout the body across multiple scales, from organs and tissues to cells and molecules, playing a vital role in maintaining tissue integrity, regulating cellular functions and supporting physiological performance. Importantly, alterations in mechanical forces and properties can be hallmarks of tissue injury and disease, and can thus serve as valuable biomarkers for disease monitoring and diagnostics and can be harnessed to modulate biological processes for therapeutic benefit. This concept, termed mechanomedicine, offers an important strategy in disease diagnosis and therapy. In this Review, we first introduce biomechanics and mechanobiology as the underlying principles of mechanomedicine and outline the properties and measurements of key mechanical signatures in health and disease. We then explore the application of mechanomedicine across scales, from organ-level and tissue-level diagnostics to cellular and molecular mechanotherapeutics, including strategies for tissue regeneration and rehabilitation. Finally, we highlight challenges and opportunities in the clinical translation of mechanomedicine approaches, in particular with regards to the innovation of materials and devices, the manufacturing of cells and organoids, the definition and standardization of mechanical biomarkers, and the integration of artificial intelligence. Mechanical forces are crucial regulators of biological functions in health and disease, offering measurable biomarkers and therapeutic targets. This Review introduces the principles of mechanomedicine and highlights its translational potential across scales, from tissue diagnostics to molecular mechanotherapeutics.","PeriodicalId":74248,"journal":{"name":"Nature reviews bioengineering","volume":"4 3","pages":"216-235"},"PeriodicalIF":37.6,"publicationDate":"2026-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147570402","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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