{"title":"Antimicrobial peptides boosted by ultrasound","authors":"Soraia Fernandes, Francesca Cavalieri","doi":"10.1038/s41551-025-01388-7","DOIUrl":"https://doi.org/10.1038/s41551-025-01388-7","url":null,"abstract":"Piezoelectric antimicrobial peptides are engineered to generate reactive oxygen species under ultrasound stimulation for treating spinal infections in goats.","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"10 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143898130","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}
Wei Jiang, Zixuan Guo, Qin Wang, Ziqi Chen, Wang Dong, Qirui Liang, Yinghong Hao, Huimin Pan, Cici Zeng, Hang Liu, Yucai Wang
{"title":"Enhanced nanoparticle delivery across vascular basement membranes of tumours using nitric oxide","authors":"Wei Jiang, Zixuan Guo, Qin Wang, Ziqi Chen, Wang Dong, Qirui Liang, Yinghong Hao, Huimin Pan, Cici Zeng, Hang Liu, Yucai Wang","doi":"10.1038/s41551-025-01385-w","DOIUrl":"https://doi.org/10.1038/s41551-025-01385-w","url":null,"abstract":"<p>The delivery of nanoparticles (NPs) into solid tumours is challenged by the tumour vascular basement membrane (BM), a critical barrier beneath the endothelium with robust mechanical properties resistant to conventional treatments. Here we propose an approach that uses nitric oxide (NO) to induce the opening of endothelial junctions, creating gaps between endothelial cells and enabling the navigation of NPs through these gaps. Subsequently, NO orchestrates a transient degradation of the BM encasing NP pools in a precise, localized action, allowing the enhanced passage of NPs into the tumour interstitial space through explosive eruptions. We have engineered a NO nanogenerator tailored for near-infrared laser-triggered on-demand NO release at tumour sites. Through breaching the BM barrier, this system results in an increase of clinical nanomedicines within the tumour, boosting the tumour suppression efficacy in both mouse and rabbit models. This approach delicately manages BM degradation, avoiding excessive degradation that might facilitate cancer metastasis. Our NO nanogenerator serves as a precise spatial catalytic degradation strategy for breaching the tumour vascular BM barrier, holding promise for NP delivery into non-tumour diseases.</p>","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"22 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143898133","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}
Xiaoguang Zhang, Xiaobo Feng, Liang Ma, Jie Lei, Gaocai Li, Weifeng Zhang, Huaizhen Liang, Bide Tong, Di Wu, Cao Yang, Lei Tan
{"title":"A sonosensitive diphenylalanine-based broad-spectrum antimicrobial peptide","authors":"Xiaoguang Zhang, Xiaobo Feng, Liang Ma, Jie Lei, Gaocai Li, Weifeng Zhang, Huaizhen Liang, Bide Tong, Di Wu, Cao Yang, Lei Tan","doi":"10.1038/s41551-025-01377-w","DOIUrl":"https://doi.org/10.1038/s41551-025-01377-w","url":null,"abstract":"<p>The antimicrobial effect of antimicrobial peptides is typically slow; they can be rapidly biodegraded and often have non-selective toxicity and elaborate sequences. Here we report a short peptide that is activated by ultrasound, that shows high broad-spectrum antibacterial efficiency (>99%) against clinically isolated methicillin-resistant bacteria (specifically, <i>Staphylococcus aureus</i>, <i>Escherichia coli</i>, <i>Staphylococcus epidermidis</i>, <i>Enterobacter cancerogenus</i> and <i>Pseudomonas aeruginosa</i>) with 15 min of ultrasound irradiation, and that has negligible toxicity and low self-antibacterial activity. We selected the peptide, FFRKSKEK (a segment from the human host-defence LL-37 peptide), from a library of peptides with piezoelectric diphenylalanine (FF) sequences, low toxicity, hydrophobicity and net positive charge. We show via all-atom molecular dynamics simulations that ultrasound amplifies the membrane-penetrating ability of peptides with FF sequences and that its piezoelectric polarization generates reactive-oxygen species and disturbs bacterial electron-transport chains. In a goat model of hard-to-treat intervertebral infection, the sonosensitive peptide led to better outcomes than vancomycin. Antimicrobial peptides activated by ultrasound may offer a clinically relevant strategy for combating antibiotic-resistant infections.</p>","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"44 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143898137","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}
Ben Wang, Jie Shen, Chenyang Huang, Zhicheng Ye, Jiajun He, Xinyu Wu, Zhiguang Guo, Li Zhang, Tiantian Xu
{"title":"Magnetically driven biohybrid blood hydrogel fibres for personalized intracranial tumour therapy under fluoroscopic tracking","authors":"Ben Wang, Jie Shen, Chenyang Huang, Zhicheng Ye, Jiajun He, Xinyu Wu, Zhiguang Guo, Li Zhang, Tiantian Xu","doi":"10.1038/s41551-025-01382-z","DOIUrl":"https://doi.org/10.1038/s41551-025-01382-z","url":null,"abstract":"<p>Small materials with pliability and untethered mobility are particularly suitable for minimally invasive medical interventions inside the body. However, the capabilities and applicability of such soft ‘robots’ are restricted by foreign-body responses to them and by the need to get them cleared from the body after the intervention. Here we report the development of biodegradable magnetized biohybrid blood hydrogel fibres that evade immune recognition, and their applicability for targeted intracranial tumour therapy with real-time tracking through X-ray fluoroscopy. The gel fibres can be made of the patient’s own blood mixed with a small amount of magnetic particles and can be produced in about 15 min. We show that the locomotion of intracranially injected gel fibres through cerebrospinal fluid can be remotely controlled under a magnetic field and fluoroscopically tracked, and that a drug encapsulated in the gels can be released on demand under magnetic control, as we show for the delivery of doxorubicin to intracranial tumours in the minipigs. Biodegradable soft actuatable materials that avoid foreign-body responses may aid the development of personalized targeted interventions.</p>","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"73 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143893289","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":"A live bacteria enzyme assay for identification of human disease mutations and drug screening","authors":"Donghui Choe, Bernhard O. Palsson","doi":"10.1038/s41551-025-01391-y","DOIUrl":"https://doi.org/10.1038/s41551-025-01391-y","url":null,"abstract":"<p>Advances in high-throughput sequencing have enabled the identification of genetic variations associated with human disease. However, deciphering the functional significance of these variations remains challenging. Here we propose an alternative approach that uses humanized <i>Escherichia coli</i> to study human genetic enzymopathies and to screen candidate drug effects on metabolic targets. By replacing selected <i>E. coli</i> metabolic enzymes with their human orthologues and their sequence variants, we demonstrate that the growth rate of <i>E. coli</i> reflects the in vivo activity of heterologously expressed human enzymes. This approach accurately reflected enzyme activities of known sequence variants, enabling rapid screening of causal sequence variations associated with human diseases. This approach bridges the gap between in vitro assays and cell-based assays. Our findings suggest that the proposed approach using a humanized <i>E. coli</i> strain holds promise for drug discovery, offering a high-throughput and cost-effective platform for identifying new compounds targeting human enzymes. Continued research and innovation in this field have the potential to impact the development and practice of precision medicine.</p>","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"35 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143889905","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}
Yoojin Kim, Yeongju Yeo, Minju Kim, Yong-Wook Son, Joowon Kim, Koung Li Kim, Seohee Kim, Seokmin Oh, Yunha Kim, Hyowoo Lee, Hyun-Woo Park, Dongsoo Lee, Sung Jin Lee, Changmin Kang, Hongyoung Choi, Chan Soon Park, Seung-Pyo Lee, Wonhee Suh, Jae-Hyung Jang
{"title":"A highly mobile adeno-associated virus targeting vascular smooth muscle cells for the treatment of pulmonary arterial hypertension","authors":"Yoojin Kim, Yeongju Yeo, Minju Kim, Yong-Wook Son, Joowon Kim, Koung Li Kim, Seohee Kim, Seokmin Oh, Yunha Kim, Hyowoo Lee, Hyun-Woo Park, Dongsoo Lee, Sung Jin Lee, Changmin Kang, Hongyoung Choi, Chan Soon Park, Seung-Pyo Lee, Wonhee Suh, Jae-Hyung Jang","doi":"10.1038/s41551-025-01379-8","DOIUrl":"https://doi.org/10.1038/s41551-025-01379-8","url":null,"abstract":"<p>In pulmonary arterial hypertension (PAH), a phenotypic switch in pulmonary arterial smooth muscle cells (PASMCs) that is primarily caused by aberrant gene regulatory networks can lead to dysregulated vascular remodelling, heart failure or death. No curative therapies for PAH are currently available, presumably because of a lack of viral vectors specifically targeting PASMCs. Here we show that a highly mobile and PASMC-tropic adeno-associated virus variant developed via directed evolution overcomes physical barriers that inhibit its transfer from bronchial airways to vascular layers, ultimately boosting therapeutic efficacy in murine models of PAH. Intratracheal administration of the adeno-associated virus variant carrying a transgene for fibroblast growth factor 12—a key factor regulating the PASMC phenotype—suppressed pulmonary vascular remodelling, prevented the development of PAH in mice and reversed established PAH in rats. The variant’s mobility and enhanced tropism for PASMCs may enable curative treatments for PAH.</p>","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"18 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143884825","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}
Alix Trouillet, Emilie Revol, Florent-Valéry Coen, Florian Fallegger, Aurélie Chanthany, Maude Delacombaz, Laurine Kolly, Ivan Furfaro, Florian Lanz, Vivek Kanumuri, Victor Adenis, Alejandro Garcia-Chavez, M. Christian Brown, Lukas Anschuetz, Jocelyne Bloch, Daniel J. Lee, Stéphanie P. Lacour
{"title":"High-resolution prosthetic hearing with a soft auditory brainstem implant in macaques","authors":"Alix Trouillet, Emilie Revol, Florent-Valéry Coen, Florian Fallegger, Aurélie Chanthany, Maude Delacombaz, Laurine Kolly, Ivan Furfaro, Florian Lanz, Vivek Kanumuri, Victor Adenis, Alejandro Garcia-Chavez, M. Christian Brown, Lukas Anschuetz, Jocelyne Bloch, Daniel J. Lee, Stéphanie P. Lacour","doi":"10.1038/s41551-025-01378-9","DOIUrl":"https://doi.org/10.1038/s41551-025-01378-9","url":null,"abstract":"<p>Individuals with compromised cochlear nerves are ineligible for cochlear implants and instead rely on auditory brainstem implants (ABIs). Most users of ABIs experience sound awareness, which aids in lip reading, yet not speech intelligibility. Here we engineered a dual-site (brainstem and cortex) implantable system, scaled to macaque anatomy, for the analysis of auditory perception evoked by electrical stimulation of the cochlear nucleus. A soft multichannel ABI, fabricated using thin-film processing, provided high-resolution auditory percepts, with spatially distinct stimulation sites eliciting cortical responses akin to frequency-specific tuning. Behavioural responses collected over several months were sufficiently precise to distinguish stimulations from adjacent channels. Soft multichannel ABIs may aid the rehabilitation of individuals with profound hearing loss who are ineligible for cochlear implants.</p>","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"17 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143846443","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}
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}
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