Matthias R. Kollert, Martin Krämer, Nicholas M. Brisson, Victoria Schemenz, Serafeim Tsitsilonis, Taimoor H. Qazi, Peter Fratzl, Viola Vogel, Jürgen R. Reichenbach, Georg N. Duda
{"title":"Water and ions binding to extracellular matrix drives stress relaxation, aiding MRI detection of swelling-associated pathology","authors":"Matthias R. Kollert, Martin Krämer, Nicholas M. Brisson, Victoria Schemenz, Serafeim Tsitsilonis, Taimoor H. Qazi, Peter Fratzl, Viola Vogel, Jürgen R. Reichenbach, Georg N. Duda","doi":"10.1038/s41551-025-01369-w","DOIUrl":"https://doi.org/10.1038/s41551-025-01369-w","url":null,"abstract":"<p>Swelling-associated changes in extracellular matrix (ECM) occur in many pathological conditions involving inflammation or oedema. Here we show that alterations in the proportion of loosely bound water in ECM correlate with changes in ECM elasticity and stress relaxation, owing to the strength of water binding to ECM being primarily governed by osmolality and the electrostatic properties of proteoglycans. By using mechanical testing and small-angle X-ray scattering, as well as magnetic resonance imaging (MRI) to detect changes in loosely bound water, we observed that enhanced water binding manifests as greater resistance to compression (mechanical or osmotic), resulting from increased electrostatic repulsion between negatively charged proteoglycans rather than axial contraction in collagen fibrils. This indicates that electrostatic contributions of proteoglycans regulate elasticity and stress relaxation independently of hydration. Our ex vivo experiments in osmotically modulated tendon elucidate physical causes of MRI signal alterations, in agreement with pilot in vivo MRI of inflammatory Achilles tendinopathy. We suggest that the strength of water binding to ECM regulates cellular niches and can be exploited to enhance MRI-informed diagnostics of swelling-associated tissue pathology.</p>","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"108 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143831751","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"An implantable hydrogel-based phononic crystal for continuous and wireless monitoring of internal tissue strains","authors":"Ye Tian, Yueying Yang, Hanchuan Tang, Jiaxin Wang, Na Li, Yifan Cheng, Tianyu Kang, Jiarui Tang, Mengyuan Zhou, Wei Chen, Yan Yu, Xinqi Liu, Xurui Liu, Liqun Xu, Zhouping Yin, Jianfeng Zang","doi":"10.1038/s41551-025-01374-z","DOIUrl":"https://doi.org/10.1038/s41551-025-01374-z","url":null,"abstract":"<p>Conventional implantable electronic sensors for continuous monitoring of internal tissue strains are yet to match the biomechanics of tissues while maintaining biodegradability, biocompatibility and wireless monitoring capability. Here we present a two-dimensional phononic crystal composed of periodic air columns in soft hydrogel, which was named ultrasonic metagel, and we demonstrate its use as implantable sensor for continuous and wireless monitoring of internal tissue strains. The metagel’s deformation shifts its ultrasonic bandgap, which can be wirelessly detected by an external ultrasonic probe. We demonstrate ex vivo the ability of the metagel sensor for monitoring tissue strains on porcine tendon, wounded tissue and heart. In live pigs, we further demonstrate the ability of the metagel to monitor tendon stretching, respiration and heartbeat, working stably during 30 days of implantation, and we loaded the metagel with growth factors to achieve different healing rates in subcutaneous wounds. The metagel results almost completely degraded 12 weeks after implantation. Our finding highlights the clinical potential of the ultrasonic sensor for tendon rehabilitation monitoring and drug delivery efficacy evaluation.</p>","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"6 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143827144","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xi Tian, Michael E. Werner, Kyle C. Roche, Ariel D. Hanson, Henry P. Foote, Stephanie K. Yu, Samuel B. Warner, Jonathan A. Copp, Haydee Lara, Eliane L. Wauthier, Joseph M. Caster, Laura E. Herring, Longzhen Zhang, Joel E. Tepper, David S. Hsu, Tian Zhang, Lola M. Reid, Andrew Z. Wang
{"title":"Author Correction: Organ-specific metastases obtained by culturing colorectal cancer cells on tissue-specific decellularized scaffolds","authors":"Xi Tian, Michael E. Werner, Kyle C. Roche, Ariel D. Hanson, Henry P. Foote, Stephanie K. Yu, Samuel B. Warner, Jonathan A. Copp, Haydee Lara, Eliane L. Wauthier, Joseph M. Caster, Laura E. Herring, Longzhen Zhang, Joel E. Tepper, David S. Hsu, Tian Zhang, Lola M. Reid, Andrew Z. Wang","doi":"10.1038/s41551-025-01383-y","DOIUrl":"https://doi.org/10.1038/s41551-025-01383-y","url":null,"abstract":"<p>Correction to: <i>Nature Biomedical Engineering</i> https://doi.org/10.1038/s41551-018-0231-0, published online 23 April 2018.</p>","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"245 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143806110","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Site-directed antibody conjugation via ubiquitination","authors":"","doi":"10.1038/s41551-025-01368-x","DOIUrl":"https://doi.org/10.1038/s41551-025-01368-x","url":null,"abstract":"The method uses ubiquitin biochemistry in vitro to achieve rapid and site-specific protein conjugation to generate homogeneous multimeric antibody conjugates. It addresses limitations of traditional conjugation methods, and it may aid the development of antibody therapies and vaccines.","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"35 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143805683","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"In vivo generation of tolerogenic APCs using PDL1 mRNA-loaded nanoparticles","authors":"","doi":"10.1038/s41551-025-01384-x","DOIUrl":"https://doi.org/10.1038/s41551-025-01384-x","url":null,"abstract":"We have developed a versatile method for generating tolerogenic antigen-presenting cells in vivo by delivering mRNA encoding PDL1 via lipid nanoparticles. These tolerogenic antigen-presenting cells selectively target and suppress activated T cells while sparing naive T cells, preventing autoimmune disease progression in mouse models.","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"10 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143806009","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Angela F. el Hebieshy, Zacharias Wijfjes, Camille M. Le Gall, Jim Middelburg, Kim E. de Roode, Felix L. Fennemann, Marjolein Sluijter, Thorbald van Hall, Douwe J. Dijkstra, Leendert A. Trouw, Floris J. van Dalen, Andrea Rodgers Furones, Johan M. S. van der Schoot, Ian Derksen, Hans de Haard, Bas van der Woning, Cami M. P. Talavera Ormeño, Bjorn R. van Doodewaerd, Carl G. Figdor, Gerbrand J. van der Heden van Noort, Paul W. H. I. Parren, Sandra Heskamp, Huib Ovaa, Martijn Verdoes, Ferenc A. Scheeren
{"title":"Site-directed multivalent conjugation of antibodies to ubiquitinated payloads","authors":"Angela F. el Hebieshy, Zacharias Wijfjes, Camille M. Le Gall, Jim Middelburg, Kim E. de Roode, Felix L. Fennemann, Marjolein Sluijter, Thorbald van Hall, Douwe J. Dijkstra, Leendert A. Trouw, Floris J. van Dalen, Andrea Rodgers Furones, Johan M. S. van der Schoot, Ian Derksen, Hans de Haard, Bas van der Woning, Cami M. P. Talavera Ormeño, Bjorn R. van Doodewaerd, Carl G. Figdor, Gerbrand J. van der Heden van Noort, Paul W. H. I. Parren, Sandra Heskamp, Huib Ovaa, Martijn Verdoes, Ferenc A. Scheeren","doi":"10.1038/s41551-024-01342-z","DOIUrl":"https://doi.org/10.1038/s41551-024-01342-z","url":null,"abstract":"<p>Antibody conjugates are the foundation of a wide range of diagnostic and therapeutic applications. Although many antibody-conjugation techniques are robust and efficient, obtaining homogeneous multimeric conjugation products remains challenging. Here we report a modular and versatile technique for the site-directed multivalent conjugation of antibodies via the small-protein ubiquitin. Specifically, multiple ubiquitin fusions with antibodies, antibody fragments, nanobodies, peptides or small molecules such as fluorescent dyes can be conjugated to antibodies and nanobodies within 30 min. The technique, which we named ‘ubi-tagging’, allowed us to efficiently generate a bispecific T-cell engager as well as nanobodies conjugated to dendritic-cell-targeted antigens that led to potent T-cell responses. Using both recombinant ubi-tagged proteins and synthetic ubiquitin derivatives allows for the iterative, site-directed and multivalent conjugation of antibodies and nanobodies to a plethora of molecular moieties.</p>","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"1 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143805684","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bin Sheng, Pearse A. Keane, Yih-Chung Tham, Tien Yin Wong
{"title":"Synthetic data boosts medical foundation models","authors":"Bin Sheng, Pearse A. Keane, Yih-Chung Tham, Tien Yin Wong","doi":"10.1038/s41551-025-01375-y","DOIUrl":"https://doi.org/10.1038/s41551-025-01375-y","url":null,"abstract":"Using synthetic data generated via conditioning with disease labels can enhance the pretraining efficiency and generalization of medical foundation models, as shown for the detection of eye diseases via fundus photographs.","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"27 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143798352","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Coordinated AI agents for advancing healthcare","authors":"Michael Moritz, Eric Topol, Pranav Rajpurkar","doi":"10.1038/s41551-025-01363-2","DOIUrl":"https://doi.org/10.1038/s41551-025-01363-2","url":null,"abstract":"Decentralized yet coordinated networks of specialized artificial intelligence agents, multi-agent systems for healthcare (MASH), that excel in performing tasks in an assistive or autonomous manner within specific clinical and operational domains are likely to become the next paradigm in medical artificial intelligence.","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"22 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143744702","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yang Liu, Qian Liu, Baowen Zhang, Shanshan Chen, Yanqiong Shen, Zhibin Li, Jiachen Zhang, Yi Yang, Min Li, Yucai Wang
{"title":"Generation of tolerogenic antigen-presenting cells in vivo via the delivery of mRNA encoding PDL1 within lipid nanoparticles","authors":"Yang Liu, Qian Liu, Baowen Zhang, Shanshan Chen, Yanqiong Shen, Zhibin Li, Jiachen Zhang, Yi Yang, Min Li, Yucai Wang","doi":"10.1038/s41551-025-01373-0","DOIUrl":"https://doi.org/10.1038/s41551-025-01373-0","url":null,"abstract":"<p>Tolerogenic antigen-presenting cells (APCs) are promising as therapeutics for suppressing T cell activation in autoimmune diseases. However, the isolation and ex vivo manipulation of autologous APCs is costly, and the process is customized for each patient. Here we show that tolerogenic APCs can be generated in vivo by delivering, via lipid nanoparticles, messenger RNA coding for the inhibitory protein programmed death ligand 1. We optimized a lipid-nanoparticle formulation to minimize its immunogenicity by reducing the molar ratio of nitrogen atoms on the ionizable lipid and the phosphate groups on the encapsulated mRNA. In mouse models of rheumatoid arthritis and ulcerative colitis, subcutaneous delivery of nanoparticles encapsulating mRNA encoding programmed death ligand 1 reduced the fraction of activated T cells, promoted the induction of regulatory T cells and effectively prevented disease progression. The method may allow for the engineering of APCs that target specific autoantigens or that integrate additional inhibitory molecules.</p>","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"95 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143723123","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}