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}
Tissue engineering-based vascular reconstruction represents a promising therapeutic strategy for ischaemic stroke. However, in the confined stroke cavity, conventional implants are unable to simultaneously provide swelling-resistant support and growth-permissive internal space, which are crucial for effective revascularization. To address this limitation, we develop a bioinspired, non-expansive biodegradable matrix (NEBM) through covalent-non-covalent assembly of commercially available, clinical-grade natural polymers. We show that NEBM recapitulates key features of brain extracellular matrix-including porous microstructure and tissue-matched stiffness-to deliver structural stability. Moreover, its progressively degradable structure establishes a dynamic remodelling niche that directs cellular behaviour towards promoting angiogenesis. Compared with commercial Matrigel-based matrix, NEBM fosters blood vessel organoid development with higher vascular density, larger vessel diameters and more distinct arterial features. In both subcutaneous and stroke transplantation models, we find that NEBM facilitates the integration of blood vessel organoids with the host vasculature. Strikingly, this revascularization in stroke cavity stimulates neurogenesis, contributing to significant functional recovery. As such, our study provides valuable guidance to design clinically translatable matrices for organ repair and regeneration in confined environments.
{"title":"Nonexpansive biodegradable matrix promotes blood vessel organoid development for neurovascular repair and functional recovery in ischaemic stroke.","authors":"Dongling Xiao,Yue Sun,Guanyuan Yang,Weixi Yan,Meilin Jiang,Zhongliang Qin,Zijun Wang,Yawei Gu,Jingting Zhou,Ju Tan,Gang Li,Yinghao Li,Chuhong Zhu","doi":"10.1038/s41551-025-01550-1","DOIUrl":"https://doi.org/10.1038/s41551-025-01550-1","url":null,"abstract":"Tissue engineering-based vascular reconstruction represents a promising therapeutic strategy for ischaemic stroke. However, in the confined stroke cavity, conventional implants are unable to simultaneously provide swelling-resistant support and growth-permissive internal space, which are crucial for effective revascularization. To address this limitation, we develop a bioinspired, non-expansive biodegradable matrix (NEBM) through covalent-non-covalent assembly of commercially available, clinical-grade natural polymers. We show that NEBM recapitulates key features of brain extracellular matrix-including porous microstructure and tissue-matched stiffness-to deliver structural stability. Moreover, its progressively degradable structure establishes a dynamic remodelling niche that directs cellular behaviour towards promoting angiogenesis. Compared with commercial Matrigel-based matrix, NEBM fosters blood vessel organoid development with higher vascular density, larger vessel diameters and more distinct arterial features. In both subcutaneous and stroke transplantation models, we find that NEBM facilitates the integration of blood vessel organoids with the host vasculature. Strikingly, this revascularization in stroke cavity stimulates neurogenesis, contributing to significant functional recovery. As such, our study provides valuable guidance to design clinically translatable matrices for organ repair and regeneration in confined environments.","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"27 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2025-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145433775","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 : 2025-10-31DOI: 10.1038/s41551-025-01534-1
Junjie Li,Kazuko Toh,Panyue Wen,Xueying Liu,Anjaneyulu Dirisala,Haochen Guo,Joachim F R Van Guyse,Saed Abbasi,Yasutaka Anraku,Yuki Mochida,Hiroaki Kinoh,Horacio Cabral,Masaru Tanaka,Kazunori Kataoka
The high interfacial energy of nanomaterials limits their certain biomedical applications that require stealthiness to minimize non-specific interaction with biological components. While steric repulsion-based entropic stabilization-such as PEGylation-has long been the dominant strategy for designing stealth nanomaterials, its inherent softness and susceptibility to dynamic deformation and external forces often result in only moderate stealth performance. Here we report a distinct approach to achieving stealthiness by harnessing an ion-pair network, rather than maximizing steric repulsion. Using model polyion complex nanoparticles composed of equimolar charge ratios of polycations and polyanions, we demonstrate that increasing crosslinks between the constituent polyions beyond a critical threshold effectively reduces protein adsorption and macrophage uptake, enabling prolonged circulation with a half-life exceeding 100 hours. Building on this, we develop an asparaginase-loaded vesicular nanoreactor enveloped by a semi-permeable ion-pair network sheath for asparagine starvation therapy. The extended circulation of these nanoreactors enables sustained depletion of asparagine, leading to improved therapeutic outcomes for metastatic breast and pancreatic cancers. Our findings open an avenue for improving the pharmacokinetics of nanomaterials for therapeutic delivery through delicately engineering stable intermolecular structures with holistic cooperativity.
{"title":"Steric stabilization-independent stealth cloak enables nanoreactors-mediated starvation therapy against refractory cancer.","authors":"Junjie Li,Kazuko Toh,Panyue Wen,Xueying Liu,Anjaneyulu Dirisala,Haochen Guo,Joachim F R Van Guyse,Saed Abbasi,Yasutaka Anraku,Yuki Mochida,Hiroaki Kinoh,Horacio Cabral,Masaru Tanaka,Kazunori Kataoka","doi":"10.1038/s41551-025-01534-1","DOIUrl":"https://doi.org/10.1038/s41551-025-01534-1","url":null,"abstract":"The high interfacial energy of nanomaterials limits their certain biomedical applications that require stealthiness to minimize non-specific interaction with biological components. While steric repulsion-based entropic stabilization-such as PEGylation-has long been the dominant strategy for designing stealth nanomaterials, its inherent softness and susceptibility to dynamic deformation and external forces often result in only moderate stealth performance. Here we report a distinct approach to achieving stealthiness by harnessing an ion-pair network, rather than maximizing steric repulsion. Using model polyion complex nanoparticles composed of equimolar charge ratios of polycations and polyanions, we demonstrate that increasing crosslinks between the constituent polyions beyond a critical threshold effectively reduces protein adsorption and macrophage uptake, enabling prolonged circulation with a half-life exceeding 100 hours. Building on this, we develop an asparaginase-loaded vesicular nanoreactor enveloped by a semi-permeable ion-pair network sheath for asparagine starvation therapy. The extended circulation of these nanoreactors enables sustained depletion of asparagine, leading to improved therapeutic outcomes for metastatic breast and pancreatic cancers. Our findings open an avenue for improving the pharmacokinetics of nanomaterials for therapeutic delivery through delicately engineering stable intermolecular structures with holistic cooperativity.","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"46 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2025-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145411638","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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