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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
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
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
Jennifer Listgarten, Michael Weinstein, Benjamin P Kleinstiver, Alexander A Sousa, J Keith Joung, Jake Crawford, Kevin Gao, Luong Hoang, Melih Elibol, John G Doench, Nicolo Fusi
The CRISPR-Cas9 system provides unprecedented genome editing capabilities. However, off-target effects lead to sub-optimal usage and additionally are a bottleneck in the development of therapeutic uses. Herein, we introduce the first machine learning-based approach to off-target prediction, yielding a state-of-the-art model for CRISPR-Cas9 that outperforms all other guide design services. Our approach, Elevation, consists of two interdependent machine learning models-one for scoring individual guide-target pairs, and another which aggregates these guide-target scores into a single, overall summary guide score...
January 2018: Nature Biomedical Engineering
Junnan Tang, Teng Su, Ke Huang, Phuong-Uyen Dinh, Zegen Wang, Adam Vandergriff, Michael T Hensley, Jhon Cores, Tyler Allen, Taosheng Li, Erin Sproul, Emily Mihalko, Leonard J Lobo, Laura Ruterbories, Alex Lynch, Ashley Brown, Thomas G Caranasos, Deliang Shen, George A Stouffer, Zhen Gu, Jinying Zhang, Ke Cheng
Stem cell transplantation, as used clinically, suffers from low retention and engraftment of the transplanted cells. Inspired by the ability of platelets to recruit stem cells to sites of injury on blood vessels, we hypothesized that platelets might enhance the vascular delivery of cardiac stem cells (CSCs) to sites of myocardial infarction injury. Here, we show that CSCs with platelet nanovesicles fused onto their surface membranes express platelet surface markers that are associated with platelet adhesion to injury sites...
2018: Nature Biomedical Engineering
Zachary Glass, Yamin Li, Qiaobing Xu
The DNA mutation that causes Duchenne muscular dystrophy in mice can be corrected, with minimal off-target effects, by gold nanoparticles carrying the CRISPR components.
November 2017: Nature Biomedical Engineering
Lauren M Baugh, Zhiyi Liu, Kyle P Quinn, Sam Osseiran, Conor L Evans, Gordon S Huggins, Philip W Hinds, Lauren D Black, Irene Georgakoudi
Calcifications occur during the development of healthy bone, and at the onset of calcific aortic-valve disease (CAVD) and many other pathologies. Although the mechanisms regulating early calcium deposition are not fully understood, they may provide targets for new treatments and for early interventions. Here, we show that two-photon excited fluorescence (TPEF) can provide quantitative and sensitive readouts of calcific nodule formation, in particular in the context of CAVD. Specifically, by means of the decomposition of TPEF spectral images from excised human CAVD valves and from rat bone prior to and following demineralization, as well as from calcific nodules formed within engineered gels, we identified an endogenous fluorophore that correlates with the level of mineralization in the samples...
November 2017: Nature biomedical engineering
Luay M Almassalha, Greta M Bauer, Wenli Wu, Lusik Cherkezyan, Di Zhang, Alexis Kendra, Scott Gladstein, John E Chandler, David VanDerway, Brandon-Luke L Seagle, Andrey Ugolkov, Daniel D Billadeau, Thomas V O'Halloran, Andrew P Mazar, Hemant K Roy, Igal Szleifer, Shohreh Shahabi, Vadim Backman
Many human diseases result from the dysregulation of the complex interactions between tens to thousands of genes. However, approaches for the transcriptional modulation of many genes simultaneously in a predictive manner are lacking. Here, through the combination of simulations, systems modelling and in vitro experiments, we provide a physical regulatory framework based on chromatin packing-density heterogeneity for modulating the genomic information space. Because transcriptional interactions are essentially chemical reactions, they depend largely on the local physical nanoenvironment...
November 2017: Nature Biomedical Engineering
Adam K Glaser, Nicholas P Reder, Ye Chen, Erin F McCarty, Chengbo Yin, Linpeng Wei, Yu Wang, Lawrence D True, Jonathan T C Liu
For the 1.7 million patients per year in the U.S. who receive a new cancer diagnosis, treatment decisions are largely made after a histopathology exam. Unfortunately, the gold standard of slide-based microscopic pathology suffers from high inter-observer variability and limited prognostic value due to sampling limitations and the inability to visualize tissue structures and molecular targets in their native 3D context. Here, we show that an open-top light-sheet microscope optimized for non-destructive slide-free pathology of clinical specimens enables the rapid imaging of intact tissues at high resolution over large 2D and 3D fields of view, with the same level of detail as traditional pathology...
July 2017: Nature Biomedical Engineering
Bin Li, Weiyu Zhao, Xiao Luo, Xinfu Zhang, Chenglong Li, Chunxi Zeng, Yizhou Dong
Cpf1, a type-V CRISPR-Cas effector endonuclease, exhibits gene-editing activity in human cells through a single RNA-guided approach. Here, we report the design and assessment of an array of 42 types of engineered Acidaminococcus sp. Cpf1 (AsCpf1) CRISPR RNAs (crRNAs) and 5 types of AsCpf1 mRNAs, and show that the top-performing modified crRNA (cr3'5F, containing five 2'-fluoro ribose at the 3' termini) and AsCpf1 mRNA (full ψ-modification) improved gene-cutting efficiency by, respectively, 127% and 177%, with respect to unmodified crRNA and plasmid-encoding AsCpf1...
May 2017: Nature biomedical engineering
Qian Wang, Dinggang Shen
Deep learning implemented in a collaborative cloud-based platform empowers ophthalmologists in the diagnosis of congenital cataracts.
February 2017: Nature Biomedical Engineering
Eric N Feins, Yuhan Lee, Eoin D O'Cearbhaill, Nikolay V Vasilyev, Shogo Shimada, Ingeborg Friehs, Douglas Perrin, Peter E Hammer, Haruo Yamauchi, Gerald Marx, Andrew Gosline, Veaceslav Arabagi, Jeffrey M Karp, Pedro J Del Nido
Medical implants of fixed size cannot accommodate normal tissue growth in children, and often require eventual replacement or in some cases removal, leading to repeated interventions, increased complication rates and worse outcomes. Implants that can correct anatomic deformities and accommodate tissue growth remain an unmet need. Here, we report the design and use of a growth-accommodating device for paediatric applications that consists of a biodegradable core and a tubular braided sleeve, with inversely related sleeve length and diameter...
2017: Nature Biomedical Engineering
Kunwoo Lee, Michael Conboy, Hyo Min Park, Fuguo Jiang, Hyun Jin Kim, Mark A Dewitt, Vanessa A Mackley, Kevin Chang, Anirudh Rao, Colin Skinner, Tamanna Shobha, Melod Mehdipour, Hui Liu, Wen-Chin Huang, Freeman Lan, Nicolas L Bray, Song Li, Jacob E Corn, Kazunori Kataoka, Jennifer A Doudna, Irina Conboy, Niren Murthy
CRISPR/Cas9-based therapeutics, especially those that can correct gene mutations via homology directed repair (HDR), have the potential to revolutionize the treatment of genetic diseases. However, HDR-based therapeutics are challenging to develop because they require simultaneous in vivo delivery of Cas9 protein, guide RNA and donor DNA. Here, we demonstrate that a delivery vehicle composed of gold nanoparticles conjugated to DNA and complexed with cationic endosomal disruptive polymers can deliver Cas9 ribonucleoprotein and donor DNA into a wide variety of cell types, and efficiently correct the DNA mutation that causes Duchenne muscular dystrophy in mice via local injection, with minimal off-target DNA damage...
2017: Nature Biomedical Engineering
Lucia R Wu, Sherry X Chen, Yalei Wu, Abhijit A Patel, David Yu Zhang
Rare DNA-sequence variants hold important clinical and biological information, but existing detection techniques are expensive, complex, allele-specific, or don't allow for significant multiplexing. Here, we report a temperature-robust polymerase-chain-reaction method, which we term blocker displacement amplification (BDA), that selectively amplifies all sequence variants, including single-nucleotide variants (SNVs), within a roughly 20-nucleotide window by 1,000-fold over wild-type sequences. This allows for easy detection and quantitation of hundreds of potential variants originally at ≤0...
2017: Nature Biomedical Engineering
Harini Kantamneni, Margot Zevon, Michael J Donzanti, Xinyu Zhao, Yang Sheng, Shravani R Barkund, Lucas H McCabe, Whitney Banach-Petrosky, Laura M Higgins, Shridar Ganesan, Richard E Riman, Charles M Roth, Mei-Chee Tan, Mark C Pierce, Vidya Ganapathy, Prabhas V Moghe
The identification and molecular profiling of early metastases remains a major challenge in cancer diagnostics and therapy. Most in vivo imaging methods fail to detect small cancerous lesions, a problem that is compounded by the distinct physical and biological barriers associated with different metastatic niches. Here, we show that intravenously injected rare-earth-doped albumin-encapsulated nanoparticles emitting short-wave infrared light (SWIR) can detect targeted metastatic lesions in vivo, allowing for the longitudinal tracking of multi-organ metastases...
2017: Nature Biomedical Engineering
T Mirabella, J W MacArthur, D Cheng, C K Ozaki, Y J Woo, M Yang, C S Chen
Arterial bypass grafts remain the gold standard for the treatment of end-stage ischaemic disease. Yet patients unable to tolerate the cardiovascular stress of arterial surgery or those with unreconstructable disease would benefit from grafts that are able to induce therapeutic angiogenesis. Here, we introduce an approach whereby implantation of 3D-printed grafts containing endothelial-cell-lined lumens induces spontaneous, geometrically guided generation of collateral circulation in ischaemic settings. In rodent models of hind-limb ischaemia and myocardial infarction, we demonstrate that the vascular patches rescue perfusion of distal tissues, preventing capillary loss, muscle atrophy and loss of function...
2017: Nature Biomedical Engineering
Guanshu Liu, Sangeeta Ray Banerjee, Xing Yang, Nirbhay Yadav, Ala Lisok, Anna Jablonska, Jiadi Xu, Yuguo Li, Martin G Pomper, Peter van Zijl
Safe imaging agents able to render the expression and distribution of cancer receptors, enzymes or other biomarkers would facilitate clinical screening of the disease. Here, we show that diamagnetic dextran particles coordinated to a urea-based targeting ligand for prostate-specific membrane antigen (PSMA) enable targeted magnetic resonance imaging (MRI) of the PSMA receptor. In a xenograft model of prostate cancer, micromolar concentrations of the dextran -ligand probe provided sufficient signal to specifically detect PSMA-expressing tumours via chemical exchange saturation transfer MRI...
2017: Nature Biomedical Engineering
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