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Nature Biomedical Engineering

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https://www.readbyqxmd.com/read/29721363/prolonged-survival-of-transplanted-stem-cells-after-ischaemic-injury-via-the-slow-release-of-pro-survival-peptides-from-a-collagen-matrix
#1
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
https://www.readbyqxmd.com/read/29456878/non-destructive-two-photon-excited-fluorescence-imaging-identifies-early-nodules-in-calcific-aortic-valve-disease
#2
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
https://www.readbyqxmd.com/read/29450107/macrogenomic-engineering-via-modulation-of-the-scaling-of-chromatin-packing-density
#3
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
https://www.readbyqxmd.com/read/29750130/light-sheet-microscopy-for-slide-free-non-destructive-pathology-of-large-clinical-specimens
#4
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
https://www.readbyqxmd.com/read/28840077/engineering-crispr-cpf1-crrnas-and-mrnas-to-maximize-genome-editing-efficiency
#5
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
https://www.readbyqxmd.com/read/29531851/surveillance-nanotechnology-for-multi-organ-cancer-metastases
#6
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
https://www.readbyqxmd.com/read/29515935/3d-printed-vascular-networks-direct-therapeutic-angiogenesis-in-ischaemia
#7
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
https://www.readbyqxmd.com/read/29456877/a-dextran-based-probe-for-the-targeted-magnetic-resonance-imaging-of-tumours-expressing-prostate-specific-membrane-antigen
#8
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
https://www.readbyqxmd.com/read/29354322/local-and-sustained-mirna-delivery-from-an-injectable-hydrogel-promotes-cardiomyocyte-proliferation-and-functional-regeneration-after-ischemic-injury
#9
Leo L Wang, Ying Liu, Jennifer J Chung, Tao Wang, Ann C Gaffey, Minmin Lu, Christina A Cavanaugh, Su Zhou, Rahul Kanade, Pavan Atluri, Edward E Morrisey, Jason A Burdick
MicroRNA-based therapies that target cardiomyocyte proliferation have great potential for the treatment of myocardial infarction (MI). In previous work, we showed that the miR-302/367 cluster regulates cardiomyocyte proliferation in the prenatal and postnatal heart. Here, we describe the development and application of an injectable hyaluronic acid (HA) hydrogel for the local and sustained delivery of miR-302 mimics to the heart. We show that the miR-302 mimics released in vitro promoted cardiomyocyte proliferation over one week, and that a single injection of the hydrogel in the mouse heart led to local and sustained cardiomyocyte proliferation for two weeks...
2017: Nature Biomedical Engineering
https://www.readbyqxmd.com/read/29354321/a-fully-functional-drug-eluting-joint-implant
#10
V J Suhardi, D A Bichara, Sjj Kwok, A A Freiberg, H Rubash, H Malchau, S H Yun, O K Muratoglu, E Oral
Despite advances in orthopedic materials, the development of drug-eluting bone and joint implants that can sustain the delivery of the drug and maintain the necessary mechanical strength in order to withstand loading has remained elusive. Here, we demonstrate that modifying the eccentricity of drug clusters and the percolation threshold in ultrahigh molecular weight polyethylene (UHMWPE) results in maximized drug elution and in the retention of mechanical strength. The optimized UHMWPE eluted antibiotic at a higher concentration for longer than the clinical gold standard antibiotic-eluting bone cement while retaining the mechanical and wear properties of clinically used UHMWPE joint prostheses...
2017: Nature Biomedical Engineering
https://www.readbyqxmd.com/read/29354320/simply-derived-epicardial-cells
#11
David T Paik, Joseph C Wu
A chemically defined protocol requiring no animal-derived components allows for the easier derivation and enduring expansion of epicardial cells from human pluripotent stem cells.
2017: Nature Biomedical Engineering
https://www.readbyqxmd.com/read/29333331/single-impulse-panoramic-photoacoustic-computed-tomography-of-small-animal-whole-body-dynamics-at-high-spatiotemporal-resolution
#12
Lei Li, Liren Zhu, Cheng Ma, Li Lin, Junjie Yao, Lidai Wang, Konstantin Maslov, Ruiying Zhang, Wanyi Chen, Junhui Shi, Lihong V Wang
Imaging of small animals has played an indispensable role in preclinical research by providing high dimensional physiological, pathological, and phenotypic insights with clinical relevance. Yet pure optical imaging suffers from either shallow penetration (up to ~1-2 mm) or a poor depth-to-resolution ratio (~1/3), and non-optical techniques for whole-body imaging of small animals lack either spatiotemporal resolution or functional contrast. Here, we demonstrate that standalone single-impulse photoacoustic computed tomography (SIP-PACT) mitigates these limitations by combining high spatiotemporal resolution (125-µm in-plane resolution, 50 µs / frame data acquisition and 50-Hz frame rate), deep penetration (48-mm cross-sectional width in vivo ), anatomical, dynamical and functional contrasts, and full-view fidelity...
2017: Nature Biomedical Engineering
https://www.readbyqxmd.com/read/29226018/conformal-phased-surfaces-for-wireless-powering-of-bioelectronic-microdevices
#13
Devansh R Agrawal, Yuji Tanabe, Desen Weng, Andrew Ma, Stephanie Hsu, Song-Yan Liao, Zhe Zhen, Zi-Yi Zhu, Chuanbowen Sun, Zhenya Dong, Fengyuan Yang, Hung Fat Tse, Ada S Y Poon, John S Ho
Wireless powering could enable the long-term operation of advanced bioelectronic devices within the human body. Although both enhanced powering depth and device miniaturization can be achieved by shaping the field pattern within the body, existing electromagnetic structures do not provide the spatial phase control required to synthesize such patterns. Here, we describe the design and operation of conformal electromagnetic structures, termed phased surfaces, that interface with non-planar body surfaces and optimally modulate the phase response to enhance the performance of wireless powering...
2017: Nature Biomedical Engineering
https://www.readbyqxmd.com/read/29204310/laser-emission-imaging-of-nuclear-biomarkers-for-high-contrast-cancer-screening-and-immunodiagnosis
#14
Yu-Cheng Chen, Xiaotian Tan, Qihan Sun, Qiushu Chen, Wenjie Wang, Xudong Fan
Detection of nuclear biomarkers such as nucleic acids and nuclear proteins is critical for early-stage cancer diagnosis and prognosis. Conventional methods relying on morphological assessment of cell nuclei in histopathology slides may be subjective, whereas colorimetric immunohistochemical and fluorescence-based imaging are limited by strong light absorption, broad-emission bands and low contrast. Here, we describe the development and use of a scanning laser-emission-based microscope that maps lasing emissions from nuclear biomarkers in human tissues...
2017: Nature Biomedical Engineering
https://www.readbyqxmd.com/read/29152410/ultrasound-triggered-local-anaesthesia
#15
Alina Y Rwei, Juan L Paris, Bruce Wang, Weiping Wang, Christopher D Axon, María Vallet-Regí, Robert Langer, Daniel S Kohane
On-demand relief of local pain would allow patients to control the timing, intensity and duration of nerve block in a safe and non-invasive manner. Ultrasound would be a suitable trigger for such a system, as it is in common clinical use and can penetrate deeply into the body. Here, we demonstrate that ultrasound-triggered delivery of an anaesthetic from liposomes allows the timing, intensity and duration of nerve block to be controlled by ultrasound parameters. On insonation, the encapsulated sonosensitizer protoporphyrin IX produces reactive oxygen species that react with the liposomal membrane, leading to the release of the potent local anaesthetic tetrodotoxin...
2017: Nature Biomedical Engineering
https://www.readbyqxmd.com/read/29152409/long-adapter-single-strand-oligonucleotide-probes-for-the-massively-multiplexed-cloning-of-kilobase-genome-regions
#16
Lorenzo Tosi, Viswanadham Sridhara, Yunlong Yang, Dongli Guan, Polina Shpilker, Nicola Segata, H Benjamin Larman, Biju Parekkadan
As the catalogue of sequenced genomes and metagenomes continues to grow, massively parallel approaches for the comprehensive and functional analysis of gene products and regulatory elements are becoming increasingly valuable. Current strategies to synthesize or clone complex libraries of DNA sequences are limited by the length of the DNA targets, throughput and cost. Here, we show that long-adapter single-strand oligonucleotide (LASSO) probes can capture and clone thousands of kilobase DNA fragments in a single reaction...
2017: Nature Biomedical Engineering
https://www.readbyqxmd.com/read/29119058/next-generation-in-vivo-optical-imaging-with-short-wave-infrared-quantum-dots
#17
Oliver T Bruns, Thomas S Bischof, Daniel K Harris, Daniel Franke, Yanxiang Shi, Lars Riedemann, Alexander Bartelt, Frank B Jaworski, Jessica A Carr, Christopher J Rowlands, Mark W B Wilson, Ou Chen, He Wei, Gyu Weon Hwang, Daniel M Montana, Igor Coropceanu, Odin B Achorn, Jonas Kloepper, Joerg Heeren, Peter T C So, Dai Fukumura, Klavs F Jensen, Rakesh K Jain, Moungi G Bawendi
For in vivo imaging, the short-wavelength infrared region (SWIR; 1000-2000 nm) provides several advantages over the visible and near-infrared regions: general lack of autofluorescence, low light absorption by blood and tissue, and reduced scattering. However, the lack of versatile and functional SWIR emitters has prevented the general adoption of SWIR imaging by the biomedical research community. Here, we introduce a class of high-quality SWIR-emissive indium-arsenide-based quantum dots (QDs) that are readily modifiable for various functional imaging applications, and that exhibit narrow and size-tunable emission and a dramatically higher emission quantum yield than previously described SWIR probes...
2017: Nature Biomedical Engineering
https://www.readbyqxmd.com/read/29104816/versatile-synthetic-alternatives-to-matrigel-for-vascular-toxicity-screening-and-stem-cell-expansion
#18
Eric H Nguyen, William T Daly, Ngoc Nhi T Le, Mitra Farnoodian, David G Belair, Michael P Schwartz, Connie S Lebakken, Gene E Ananiev, Mohammad Ali Saghiri, Thomas B Knudsen, Nader Sheibani, William L Murphy
The physiological relevance of Matrigel as a cell-culture substrate and in angiogenesis assays is often called into question. Here, we describe an array-based method for the identification of synthetic hydrogels that promote the formation of robust in vitro vascular networks for the detection of putative vascular disruptors, and that support human embryonic stem cell expansion and pluripotency. We identified hydrogel substrates that promoted endothelial-network formation by primary human umbilical vein endothelial cells and by endothelial cells derived from human induced pluripotent stem cells, and used the hydrogels with endothelial networks to identify angiogenesis inhibitors...
2017: Nature Biomedical Engineering
https://www.readbyqxmd.com/read/29082104/dramatic-enhancement-of-the-detection-limits-of-bioassays-via-ultrafast-deposition-of-polydopamine
#19
Junwei Li, Madison A Baird, Michael A Davis, Wanyi Tai, Larry S Zweifel, Kristina M Adams Waldorf, Michael Gale, Lakshmi Rajagopal, Robert H Pierce, Xiaohu Gao
The ability to detect biomarkers with ultrahigh sensitivity radically transformed biology and disease diagnosis. However, owing to incompatibilities with infrastructure in current biological and medical laboratories, recent innovations in analytical technology have not received broad adoption. Here, we report a simple, universal 'add-on' technology (dubbed EASE) that can be directly plugged into the routine practices of current research and clinical laboratories and that converts the ordinary sensitivities of common bioassays to extraordinary ones...
2017: Nature Biomedical Engineering
https://www.readbyqxmd.com/read/29062587/one-week-glucose-control-via-zero-order-release-kinetics-from-an-injectable-depot-of-glucagon-like-peptide-1-fused-to-a-thermosensitive-biopolymer
#20
Kelli M Luginbuhl, Jeffrey L Schaal, Bret Umstead, Eric M Mastria, Xinghai Li, Samagya Banskota, Susan Arnold, Mark Feinglos, David D'Alessio, Ashutosh Chilkoti
Stimulation of the glucagon-like peptide-1 (GLP1) receptor is a useful treatment strategy for type 2 diabetes because of pleiotropic effects, including the regulation of islet hormones and the induction of satiety. However, the native ligand for the GLP1 receptor has a short half-live owing to enzymatic inactivation and rapid clearance. Here, we show that a subcutaneous depot formed after a single injection of GLP1 recombinantly fused to a thermosensitive elastin-like polypeptide results in zero-order release kinetics and circulation times of up to 10 days in mice and 17 days in monkeys...
2017: Nature Biomedical Engineering
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