Pub Date : 2025-11-17DOI: 10.1038/s41551-025-01572-9
A key aspect of biomedical advancement is improving over the state of the art. We provide guidance on our expectations for benchmarking at Nature Biomedical Engineering and encourage authors to think ahead about including crucial comparative experiments.
{"title":"Benchmarking matters","authors":"","doi":"10.1038/s41551-025-01572-9","DOIUrl":"10.1038/s41551-025-01572-9","url":null,"abstract":"A key aspect of biomedical advancement is improving over the state of the art. We provide guidance on our expectations for benchmarking at Nature Biomedical Engineering and encourage authors to think ahead about including crucial comparative experiments.","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"9 11","pages":"1789-1790"},"PeriodicalIF":26.8,"publicationDate":"2025-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41551-025-01572-9.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145533774","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-14DOI: 10.1038/s41551-025-01520-7
Jack Chen, Patricia Jastrzebska-Perfect, Peter Chai, Mehmet Girayhan Say, Jiaobing Tu, Wei Gao, Florencia Halperin, Joshua Korzenik, Hen-Wei Huang, Dina Katabi, Giovanni Traverso
While treatment remains essential, disease prevention often proves more effective in improving outcomes, enhancing well-being and reducing healthcare costs. Despite this understanding, preventative medical practices are still underutilized. Continuous monitoring technologies can help to address this gap by enabling early symptom detection, tracking disease recurrence and assessing treatment responses, yet few of the technologies have been integrated into clinical practice. In this Review, we discuss notable advances in continuous monitoring and the barriers to their translation. We focus on technologies that enable either continuous measurement for at least one week or periodic measurements for at least one month, including remotely interfacing technologies, wearables and other directly interfacing systems, and internally interfacing implanted devices. Continuous monitoring improves disease-risk assessment, tracks disease progression and enhances overall health management. However, broader and more reliable datasets from diverse clinical trials, alongside supportive policies and financial incentives, will be essential to overcoming translational barriers and to integrating these technologies into healthcare. This Review discusses how continuous monitoring technologies can enable early symptom detection, disease recurrence tracking and treatment response assessment, and how these technologies are being integrated into clinical practice.
{"title":"Barriers to translating continuous monitoring technologies for preventative medicine","authors":"Jack Chen, Patricia Jastrzebska-Perfect, Peter Chai, Mehmet Girayhan Say, Jiaobing Tu, Wei Gao, Florencia Halperin, Joshua Korzenik, Hen-Wei Huang, Dina Katabi, Giovanni Traverso","doi":"10.1038/s41551-025-01520-7","DOIUrl":"10.1038/s41551-025-01520-7","url":null,"abstract":"While treatment remains essential, disease prevention often proves more effective in improving outcomes, enhancing well-being and reducing healthcare costs. Despite this understanding, preventative medical practices are still underutilized. Continuous monitoring technologies can help to address this gap by enabling early symptom detection, tracking disease recurrence and assessing treatment responses, yet few of the technologies have been integrated into clinical practice. In this Review, we discuss notable advances in continuous monitoring and the barriers to their translation. We focus on technologies that enable either continuous measurement for at least one week or periodic measurements for at least one month, including remotely interfacing technologies, wearables and other directly interfacing systems, and internally interfacing implanted devices. Continuous monitoring improves disease-risk assessment, tracks disease progression and enhances overall health management. However, broader and more reliable datasets from diverse clinical trials, alongside supportive policies and financial incentives, will be essential to overcoming translational barriers and to integrating these technologies into healthcare. This Review discusses how continuous monitoring technologies can enable early symptom detection, disease recurrence tracking and treatment response assessment, and how these technologies are being integrated into clinical practice.","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"9 11","pages":"1797-1815"},"PeriodicalIF":26.8,"publicationDate":"2025-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145508898","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}
Pub Date : 2025-11-03DOI: 10.1038/s41551-025-01543-0
Rohan Bhattacharya,Tarsha Ward,Titilola D Kalejaiye,Alekshyander Mishra,Sophia M Leeman,Hamidreza Arzaghi,Jonathan G Seidman,Christine E Seidman,Samira Musah
Clinical observations of patients with congenital heart disease carrying SMAD2 genetic variants revealed correlations with multi-organ impairments at the developmental and functional levels. Many patients with congenital heart disease present with glomerulosclerosis, periglomerular fibrosis and albuminuria. It remains largely unknown whether SMAD2 variants associated with congenital heart disease can directly alter kidney cell fate, tissue patterning and organ-level function. Here we investigate the role of pathogenic SMAD2 variants in podocytogenesis, nephrogenic cell lineage specification and glomerular filtration barrier function using a combination of CRISPR-based disease modelling, stem cell and microfluidic organ-on-a-chip technologies. We show that the abrogation of SMAD2 results in altered patterning of the mesoderm and intermediate mesoderm cell lineages, which give rise to nearly all kidney cell types. Following further differentiation of intermediate mesoderm cells, the mutant podocytes failed to develop arborizations and interdigitations. A reconstituted glomerulus-on-a-chip system showed substantial albumin leakage, as observed in glomerulopathies. This study implicates chronic heart disease-associated SMAD2 mutations in kidney tissue malformation that might inform targeted regenerative therapies.
{"title":"Engineered human induced pluripotent stem cell models reveal altered podocytogenesis in congenital heart disease-associated SMAD2 mutations.","authors":"Rohan Bhattacharya,Tarsha Ward,Titilola D Kalejaiye,Alekshyander Mishra,Sophia M Leeman,Hamidreza Arzaghi,Jonathan G Seidman,Christine E Seidman,Samira Musah","doi":"10.1038/s41551-025-01543-0","DOIUrl":"https://doi.org/10.1038/s41551-025-01543-0","url":null,"abstract":"Clinical observations of patients with congenital heart disease carrying SMAD2 genetic variants revealed correlations with multi-organ impairments at the developmental and functional levels. Many patients with congenital heart disease present with glomerulosclerosis, periglomerular fibrosis and albuminuria. It remains largely unknown whether SMAD2 variants associated with congenital heart disease can directly alter kidney cell fate, tissue patterning and organ-level function. Here we investigate the role of pathogenic SMAD2 variants in podocytogenesis, nephrogenic cell lineage specification and glomerular filtration barrier function using a combination of CRISPR-based disease modelling, stem cell and microfluidic organ-on-a-chip technologies. We show that the abrogation of SMAD2 results in altered patterning of the mesoderm and intermediate mesoderm cell lineages, which give rise to nearly all kidney cell types. Following further differentiation of intermediate mesoderm cells, the mutant podocytes failed to develop arborizations and interdigitations. A reconstituted glomerulus-on-a-chip system showed substantial albumin leakage, as observed in glomerulopathies. This study implicates chronic heart disease-associated SMAD2 mutations in kidney tissue malformation that might inform targeted regenerative therapies.","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"4 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2025-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145433771","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}
Pub Date : 2025-11-03DOI: 10.1038/s41551-025-01559-6
{"title":"A modified nanoparticle-mRNA complex for improved gene editing in the heart.","authors":"","doi":"10.1038/s41551-025-01559-6","DOIUrl":"https://doi.org/10.1038/s41551-025-01559-6","url":null,"abstract":"","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"35 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2025-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145433772","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}
Pub Date : 2025-11-03DOI: 10.1038/s41551-025-01523-4
Gabriel Neiman,Mauro W Costa,Hesong Han,Sheng Zhao,Tammy K Ng,Brian Siemons,Tomohiro Nishino,Yu Huang,Shyam Lal,Kenneth Wu,Luke M Judge,Bruce R Conklin,Deepak Srivastava,Niren Murthy,Kevin E Healy
Gene transfection via lipid nanoparticle (LNP)-mRNA complexes have tremendous potential for treating cardiac diseases. However, the transfection efficiency is poor and there is a lack of in vitro screening systems that predict transfection efficacy. Here we demonstrate a method for identifying LNP-mRNA complexes that diffuse efficiently within 3D cardiac micromuscles and transfect cardiomyocytes with high efficiency, using a phenotypic cardiac microphysiological system (MPS) constructed from a human induced pluripotent stem cell cardiomyocytes Cre-reporter line. LNP formulations containing an acid-degradable PEG-lipid had enhanced diffusion and gene editing efficiency in the cardiac MPS. The in vivo delivery of LNP-mRNA complexes, including luciferase and CRE mRNA, into Ai6 mice confirmed the cardiac MPS screening outcomes. Acid-degradable PEG-LNPs achieved notably superior transfection in the heart with reduced off-target liver uptake compared with standard LNP formulations. The cardiac MPS showed strong LNP transfection in vitro and pinpointed a promising formulation for in vivo mRNA delivery to the heart.
{"title":"A microphysiological system for screening lipid nanoparticle-mRNA complexes predicts in vivo heart transfection efficacy.","authors":"Gabriel Neiman,Mauro W Costa,Hesong Han,Sheng Zhao,Tammy K Ng,Brian Siemons,Tomohiro Nishino,Yu Huang,Shyam Lal,Kenneth Wu,Luke M Judge,Bruce R Conklin,Deepak Srivastava,Niren Murthy,Kevin E Healy","doi":"10.1038/s41551-025-01523-4","DOIUrl":"https://doi.org/10.1038/s41551-025-01523-4","url":null,"abstract":"Gene transfection via lipid nanoparticle (LNP)-mRNA complexes have tremendous potential for treating cardiac diseases. However, the transfection efficiency is poor and there is a lack of in vitro screening systems that predict transfection efficacy. Here we demonstrate a method for identifying LNP-mRNA complexes that diffuse efficiently within 3D cardiac micromuscles and transfect cardiomyocytes with high efficiency, using a phenotypic cardiac microphysiological system (MPS) constructed from a human induced pluripotent stem cell cardiomyocytes Cre-reporter line. LNP formulations containing an acid-degradable PEG-lipid had enhanced diffusion and gene editing efficiency in the cardiac MPS. The in vivo delivery of LNP-mRNA complexes, including luciferase and CRE mRNA, into Ai6 mice confirmed the cardiac MPS screening outcomes. Acid-degradable PEG-LNPs achieved notably superior transfection in the heart with reduced off-target liver uptake compared with standard LNP formulations. The cardiac MPS showed strong LNP transfection in vitro and pinpointed a promising formulation for in vivo mRNA delivery to the heart.","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"130 4 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2025-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145433773","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}
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