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Nature Biomedical Engineering

Mark Juhas, Nadia Abutaleb, Jason T Wang, Jean Ye, Zohaib Shaikh, Chaichontat Sriworarat, Ying Qian, Nenad Bursac
Adult skeletal muscle has a robust capacity for self-repair, owing to synergies between muscle satellite cells and the immune system. In vitro models of muscle self-repair would facilitate the basic understanding of muscle regeneration and the screening of therapies for muscle disease. Here, we show that the incorporation of macrophages into muscle tissues engineered from adult-rat myogenic cells enables near-complete structural and functional repair after cardiotoxic injury in vitro. First, we show that-in contrast with injured neonatal-derived engineered muscle-adult-derived engineered muscle fails to properly self-repair after injury, even when treated with pro-regenerative cytokines...
December 2018: Nature Biomedical Engineering
Dawei Jiang, Zhilei Ge, Hyung-Jun Im, Christopher G England, Dalong Ni, Junjun Hou, Luhao Zhang, Christopher J Kutyreff, Yongjun Yan, Yan Liu, Steve Y Cho, Jonathan W Engle, Jiye Shi, Peng Huang, Chunhai Fan, Hao Yan, Weibo Cai
Patients with acute kidney injury (AKI) frequently require kidney transplantation and supportive therapies, such as rehydration and dialysis. Here, we show that radiolabelled DNA origami nanostructures (DONs) with rectangular, triangular and tubular shapes accumulate preferentially in the kidneys of healthy mice and mice with rhabdomyolysis-induced AKI, and that rectangular DONs have renal-protective properties, with efficacy similar to the antioxidant N -acetylcysteine-a clinically used drug that ameliorates contrast-induced AKI and protects kidney function from nephrotoxic agents...
November 2018: Nature biomedical engineering
Hyungsoon Im, Divya Pathania, Philip J McFarland, Aliyah R Sohani, Ismail Degani, Matthew Allen, Benjamin Coble, Aoife Kilcoyne, Seonki Hong, Lucas Rohrer, Jeremy S Abramson, Scott Dryden-Peterson, Lioubov Fexon, Mikhail Pivovarov, Bruce Chabner, Hakho Lee, Cesar M Castro, Ralph Weissleder
The identification of patients with aggressive cancer who require immediate therapy is a health challenge in low-income and middle-income countries. Limited pathology resources, high healthcare costs and large-case loads call for the development of advanced standalone diagnostics. Here, we report and validate an automated, low-cost point-of-care device for the molecular diagnosis of aggressive lymphomas. The device uses contrast-enhanced microholography and a deep-learning algorithm to directly analyse percutaneously obtained fine-needle aspirates...
September 2018: Nature Biomedical Engineering
Ophir Vermesh, Amin Aalipour, T Jessie Ge, Yamil Saenz, Yue Guo, Israt S Alam, Seung-Min Park, Charlie N Adelson, Yoshiaki Mitsutake, Jose Vilches-Moure, Elias Godoy, Michael H Bachmann, Chin Chun Ooi, Jennifer K Lyons, Kerstin Mueller, Hamed Arami, Alfredo Green, Edward I Solomon, Shan X Wang, Sanjiv S Gambhir
The detection and analysis of rare blood biomarkers is necessary for early diagnosis of cancer and to facilitate the development of tailored therapies. However, current methods for the isolation of circulating tumour cells (CTCs) or nucleic acids present in a standard clinical sample of only 5-10 ml of blood provide inadequate yields for early cancer detection and comprehensive molecular profiling. Here, we report the development of a flexible magnetic wire that can retrieve rare biomarkers from the subject's blood in vivo at a much higher yield...
September 2018: Nature Biomedical Engineering
Halil Tekin, Sean Simmons, Beryl Cummings, Linyi Gao, Xian Adiconis, Cynthia C Hession, Ayan Ghoshal, Danielle Dionne, Sourav R Choudhury, Volkan Yesilyurt, Neville E Sanjana, Xi Shi, Congyi Lu, Matthias Heidenreich, Jen Q Pan, Joshua Z Levin, Feng Zhang
Understanding neurological diseases requires tractable genetic systems. Engineered 3D neural tissues are an attractive choice, but how the cellular transcriptomic profiles in these tissues are affected by the encapsulating materials and are related to the human-brain transcriptome is not well understood. Here, we report the characterization of the effects of culturing conditions on the transcriptomic profiles of induced neuronal cells, as well as a method for the rapid generation of 3D co-cultures of neuronal and astrocytic cells from the same pool of human embryonic stem cells...
July 2018: Nature Biomedical Engineering
T L Edwards, K Xue, H C M Meenink, M J Beelen, G J L Naus, M P Simunovic, M Latasiewicz, A D Farmery, M D de Smet, R E MacLaren
Microsurgery of the retina would be dramatically improved by instruments that offer supra-human precision. Here, we report the results of a first-in-human study of remotely controlled robot-assisted retinal surgery performed through a telemanipulation device. Specifically, 12 patients requiring dissection of the epiretinal or inner limiting membrane over the macula were randomly assigned to either undergo robot-assisted-surgery or manual surgery, under general anaesthesia. We evaluated surgical success, duration of surgery and amount of retinal microtrauma as a proxy for safety...
June 18, 2018: Nature Biomedical Engineering
Eduardo Marbán
The development of cells for regenerative therapy has encountered many pitfalls on its path to clinical translation. In cardiology, clinical studies of heart-targeted cell therapies began two decades ago, yet progress towards reaching an approved product has been slow. In this Perspective, I provide an overview of recent cardiac cell therapies, with a focus on the hurdles limiting the translation of cell products from research laboratories to clinical practice. By focusing on heart failure as a target indication, I argue that strategies for overcoming limitations in clinical translation require an increasing emphasis on mechanism-supported efficacy, rather than on phenomenological observations...
June 2018: Nature Biomedical Engineering
Holly M Poling, David Wu, Nicole Brown, Michael Baker, Taylor A Hausfeld, Nhan Huynh, Samuel Chaffron, James C Y Dunn, Simon P Hogan, James M Wells, Michael A Helmrath, Maxime M Mahe
The natural ability of stem cells to self-organize into functional tissue has been harnessed for the production of functional human intestinal organoids. Although dynamic mechanical forces play a central role in intestinal development and morphogenesis, conventional methods for the generation of intestinal organoids have relied solely on biological factors. Here, we show that the incorporation of uniaxial strain, by using compressed nitinol springs, in human intestinal organoids transplanted into the mesentery of mice induces growth and maturation of the organoids...
June 2018: Nature Biomedical Engineering
Mansi Saxena, Sreekumar Balan, Vladimir Roudko, Nina Bhardwaj
No abstract text is available yet for this article.
June 2018: Nature Biomedical Engineering
Bohao Liu, Benjamin W Lee, Koki Nakanishi, Aranzazu Villasante, Rebecca Williamson, Jordan Metz, Jinho Kim, Mariko Kanai, Lynn Bi, Kristy Brown, Gilbert Di Paolo, Shunichi Homma, Peter A Sims, Veli K Topkara, Gordana Vunjak-Novakovic
The ability of extracellular vesicles (EVs) to regulate a broad range of cellular processes has recently been exploited for the treatment of diseases. For example, EVs secreted by stem cells injected into infarcted hearts can induce recovery through the delivery of stem-cell-specific miRNAs. However, the retention of the EVs and the therapeutic effects are short-lived. Here, we show that an engineered hydrogel patch capable of slowly releasing EVs secreted from cardiomyocytes derived from induced pluripotent stem (iPS) cells reduced arrhythmic burden, promoted ejection-fraction recovery, decreased cardiomyocyte apoptosis 24 hours after infarction, and reduced infarct size and cell hypertrophy 4 weeks post-infarction when implanted onto infarcted rat hearts...
May 2018: Nature Biomedical Engineering
Felix Ellett, Julianne Jorgensen, Anika L Marand, Yuk M Liu, Myriam M Martinez, Vicki Sein, Kathryn L Butler, Jarone Lee, Daniel Irimia
Current methods for the diagnosis of sepsis have insufficient precision, causing regular misdiagnoses. Microbiological tests can help diagnose sepsis but are usually too slow to have an impact on timely clinical-decision making. Neutrophils have high sensitivity to infections, yet measurements of neutrophil surface markers, genomic changes, and phenotype alterations have had only a marginal effect on sepsis diagnosis. Here, we report a microfluidic assay that measures the spontaneous motility of neutrophils in the context of plasma, in one droplet of blood...
April 2018: Nature Biomedical Engineering
Anthony G Christodoulou, Jaime L Shaw, Christopher Nguyen, Qi Yang, Yibin Xie, Nan Wang, Debiao Li
Quantitative cardiovascular magnetic resonance (CMR) imaging can be used to characterize fibrosis, oedema, ischaemia, inflammation and other disease conditions. However, the need to reduce artefacts arising from body motion through a combination of electrocardiography (ECG) control, respiration control, and contrast-weighting selection makes CMR exams lengthy. Here, we show that physiological motions and other dynamic processes can be conceptualized as multiple time dimensions that can be resolved via low-rank tensor imaging, allowing for motion-resolved quantitative imaging with up to four time dimensions...
April 2018: Nature Biomedical Engineering
Sai Ma, Mario de la Fuente Revenga, Zhixiong Sun, Chen Sun, Travis W Murphy, Hehuang Xie, Javier González-Maeso, Chang Lu
Methylomic analyses typically require substantial amounts of DNA, thus hindering studies involving scarce samples. Here, we show that microfluidic diffusion-based reduced representative bisulfite sequencing (MID-RRBS) permits high-quality methylomic profiling with nanogram-to-single-cell quantities of starting DNA. We used the microfluidic device, which allows for efficient bisulfite conversion with high DNA recovery, to analyse genome-wide DNA methylation in cell nuclei isolated from mouse brains and sorted into NeuN+ (primarily neuronal) and NeuN- (primarily glial) fractions, and to establish cell-type-specific methylomes...
March 2018: Nature Biomedical Engineering
Sazid Hussain, Jinmyoung Joo, Jinyoung Kang, Byungji Kim, Gary B Braun, Zhi-Gang She, Dokyoung Kim, Aman P Mann, Tarmo Mölder, Tambet Teesalu, Santina Carnazza, Salvatore Guglielmino, Michael J Sailor, Erkki Ruoslahti
Bacterial resistance to antibiotics has made it necessary to resort to antibiotics that have considerable toxicities. Here, we show that the cyclic 9-amino acid peptide CARGGLKSC (CARG), identified via phage display on Staphylococcus aureus ( S. aureus ) bacteria and through in vivo screening in mice with S. aureus -induced lung infections, increases the antibacterial activity of CARG-conjugated vancomycin-loaded nanoparticles in S. aureus -infected tissues and reduces the needed overall systemic dose, minimizing side effects...
February 2018: Nature Biomedical Engineering
Andrew S Lee, Mohammed Inayathullah, Maarten A Lijkwan, Xin Zhao, Wenchao Sun, Sujin Park, Wan Xing Hong, Mansi B Parekh, Andrey V Malkovskiy, Edward Lau, Xulei Qin, Venkata Raveendra Pothineni, Verónica Sanchez-Freire, Wendy Y Zhang, Nigel G Kooreman, Antje D Ebert, Charles K F Chan, Patricia K Nguyen, Jayakumar Rajadas, Joseph C Wu
Stem-cell-based therapies hold considerable promise for regenerative medicine. However, acute donor-cell death within several weeks after cell delivery remains a critical hurdle for clinical translation. Co-transplantation of stem cells with pro-survival factors can improve cell engraftment, but this strategy has been hampered by the typically short half-lives of the factors and by the use of Matrigel and other scaffolds that are not chemically defined. Here, we report a collagen-dendrimer biomaterial crosslinked with pro-survival peptide analogues that adheres to the extracellular matrix and slowly releases the peptides, significantly prolonging stem cell survival in mouse models of ischaemic injury...
February 2018: Nature Biomedical Engineering
Yongzhi Qiu, Byungwook Ahn, Yumiko Sakurai, Caroline Hansen, Reginald Tran, Patrice N Mimche, Robert Mannino, Jordan C Ciciliano, Tracey J Lamb, Clinton H Joiner, Solomon F Ofori-Acquah, Wilbur A Lam
Alterations in the mechanical properties of erythrocytes occurring in inflammatory and hematologic disorders such as sickle cell disease (SCD) and malaria often lead to increased endothelial permeability, haemolysis, and microvascular obstruction. However, the associations among these pathological phenomena remain unknown. Here, we report a perfusable, endothelialized microvasculature-on-a-chip featuring an interpenetrating-polymer-network hydrogel that recapitulates the stiffness of blood-vessel intima, basement membrane self-deposition and self-healing endothelial barrier function for longer than 1 month...
2018: Nature Biomedical Engineering
Ophir Vermesh, Amin Aalipour, T Jessie Ge, Yamil Saenz, Yue Guo, Israt S Alam, Seung-Min Park, Charlie N Adelson, Yoshiaki Mitsutake, Jose Vilches-Moure, Elias Godoy, Michael Bachmann, Chin Chun Ooi, Jennifer K Lyons, Kerstin Mueller, Hamed Arami, Alfredo Green, Edward I Solomon, Shan X Wang, Sanjiv S Gambhir
The detection and analysis of rare blood biomarkers is necessary for early cancer diagnosis and to facilitate the development of tailored therapies. However, current methods for the isolation of circulating tumor cells (CTCs) or nucleic acids present in a standard clinical sample of only 5-10 mL of blood provide inadequate yields for early cancer detection and comprehensive molecular profiling. We have developed a flexible magnetic wire that can retrieve rare biomarkers from the subject's blood in vivo at a much higher yield...
2018: Nature Biomedical Engineering
Christopher B Rodell, Sean P Arlauckas, Michael F Cuccarese, Christopher S Garris, Ran Li, Maaz S Ahmed, Rainer H Kohler, Mikael J Pittet, Ralph Weissleder
Tumour-associated macrophages (TAMs) are abundant in many cancers, and often display an immune-suppressive M2-like phenotype that fosters tumour growth and promotes resistance to therapy. Yet macrophages are highly plastic and can also acquire an anti-tumourigenic M1-like phenotype. Here, we show that R848, an agonist of the toll-like receptors (TLRs) TLR7 and TLR8 identified in a morphometric-based screen, is a potent driver of the M1 phenotype in vitro and that R848-loaded β-cyclodextrin nanoparticles (CDNPs) lead to efficient drug delivery to TAMs in vivo...
2018: Nature Biomedical Engineering
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
Metastatic disease remains the primary cause of mortality in cancer patients. Yet the number of available in vitro models to study metastasis is limited by challenges in the recapitulation of the metastatic microenvironment in vitro , and by difficulties in maintaining colonized-tissue specificity in the expansion and maintenance of metastatic cells. Here, we show that decellularized scaffolds that retain tissue-specific extracellular-matrix (ECM) components and bound signaling molecules enable, when seeded with colorectal cancer (CRC) cells, the spontaneous formation of three-dimensional cell colonies that histologically, molecularly and phenotypically resemble in vivo metastases...
2018: Nature biomedical engineering
Wanyi Tai, Junwei Li, Eva Corey, Xiaohu Gao
Hurdles in cell-specific delivery of small interfering RNA (siRNA) in vivo hinder the clinical translation of RNA interference (RNAi). A fundamental problem concerns conflicting requirements for the design of the delivery vehicles: cationic materials facilitate cargo condensation and endosomolysis, yet hinder in vivo targeting and colloidal stability. Here, we describe a self-assembled, compact (~30 nm) and biocompatible ribonucleoprotein-octamer nanoparticle that achieves endosomal destabilization and targeted delivery...
2018: Nature Biomedical Engineering
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