scholarly journals Miniature in vivo MEMS-based line-scanned dual-axis confocal microscope for point-of-care pathology

2016 ◽  
Vol 7 (2) ◽  
pp. 251 ◽  
Author(s):  
C. Yin ◽  
A.K. Glaser ◽  
S. Y. Leigh ◽  
Y. Chen ◽  
L. Wei ◽  
...  
2005 ◽  
Vol 43 (05) ◽  
Author(s):  
M Goetz ◽  
MF Neurath ◽  
P Delaney ◽  
S Gregor ◽  
D Strand ◽  
...  
Keyword(s):  

2021 ◽  
Vol 9 (5) ◽  
pp. e001925
Author(s):  
Shujuan Zhou ◽  
Fanyan Meng ◽  
Shiyao Du ◽  
Hanqing Qian ◽  
Naiqing Ding ◽  
...  

BackgroundPoor infiltration and limited activation of transferred T cells are fundamental factors impeding the development of adoptive cell immunotherapy in solid tumors. A tumor-penetrating peptide iRGD has been widely used to deliver drugs deep into tumor tissues. CD3-targeting bispecific antibodies represent a promising immunotherapy which recruits and activates T cells.MethodsT-cell penetration was demonstrated in tumor spheroids using confocal microscope, and in xenografted tumors by histology and in vivo real-time fluorescence imaging. Activation and cytotoxicity of T cells were assessed by flow cytometry and confocal microscope. Bioluminescence imaging was used to evaluate in vivo antitumor effects, and transmission electron microscopy was used for mechanistic studies.ResultsWe generated a novel bifunctional agent iRGD-anti-CD3 which could immobilize iRGD on the surface of T cells through CD3 engaging. We found that iRGD-anti-CD3 modification not only facilitated T-cell infiltration in 3D tumor spheroids and xenografted tumor nodules but also induced T-cell activation and cytotoxicity against target cancer cells. T cells modified with iRGD-anti-CD3 significantly inhibited tumor growth and prolonged survival in several xenograft mouse models, which was further enhanced by the combination of programmed cell death protein 1 (PD-1) blockade. Mechanistic studies revealed that iRGD-anti-CD3 initiated a transport pathway called vesiculovacuolar organelles in the endothelial cytoplasm to promote T-cell extravasation.ConclusionAltogether, we show that iRGD-anti-CD3 modification is an innovative and bifunctional strategy to overcome major bottlenecks in adoptive cell therapy. Moreover, we demonstrate that combination with PD-1 blockade can further improve antitumor efficacy of iRGD-anti-CD3-modified T cells.


2017 ◽  
Vol 22 (5) ◽  
pp. 056008 ◽  
Author(s):  
Cory Olsovsky ◽  
Taylor Hinsdale ◽  
Rodrigo Cuenca ◽  
Yi-Shing Lisa Cheng ◽  
John M. Wright ◽  
...  

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Weixian Xi ◽  
Vishal Hegde ◽  
Stephen D. Zoller ◽  
Howard Y. Park ◽  
Christopher M. Hart ◽  
...  

AbstractImplant related infections are the most common cause of joint arthroplasty failure, requiring revision surgeries and a new implant, resulting in a cost of $8.6 billion annually. To address this problem, we created a class of coating technology that is applied in the operating room, in a procedure that takes less than 10 min, and can incorporate any desired antibiotic. Our coating technology uses an in situ coupling reaction of branched poly(ethylene glycol) and poly(allyl mercaptan) (PEG-PAM) polymers to generate an amphiphilic polymeric coating. We show in vivo efficacy in preventing implant infection in both post-arthroplasty infection and post-spinal surgery infection mouse models. Our technology displays efficacy with or without systemic antibiotics, the standard of care. Our coating technology is applied in a clinically relevant time frame, does not require modification of implant manufacturing process, and does not change the implant shelf life.


Author(s):  
Pramila Thapa ◽  
Hansha Pandey ◽  
Veena Singh ◽  
Shilpa Tayal ◽  
Anurag Shrivastava ◽  
...  

2020 ◽  
Vol 6 (33) ◽  
pp. eabb5093 ◽  
Author(s):  
Fiona E. Freeman ◽  
Pierluca Pitacco ◽  
Lieke H. A. van Dommelen ◽  
Jessica Nulty ◽  
David C. Browe ◽  
...  

Therapeutic growth factor delivery typically requires supraphysiological dosages, which can cause undesirable off-target effects. The aim of this study was to 3D bioprint implants containing spatiotemporally defined patterns of growth factors optimized for coupled angiogenesis and osteogenesis. Using nanoparticle functionalized bioinks, it was possible to print implants with distinct growth factor patterns and release profiles spanning from days to weeks. The extent of angiogenesis in vivo depended on the spatial presentation of vascular endothelial growth factor (VEGF). Higher levels of vessel invasion were observed in implants containing a spatial gradient of VEGF compared to those homogenously loaded with the same total amount of protein. Printed implants containing a gradient of VEGF, coupled with spatially defined BMP-2 localization and release kinetics, accelerated large bone defect healing with little heterotopic bone formation. This demonstrates the potential of growth factor printing, a putative point of care therapy, for tightly controlled tissue regeneration.


mBio ◽  
2014 ◽  
Vol 5 (2) ◽  
Author(s):  
Mamoudou Maiga ◽  
Seong Won Choi ◽  
Viorel Atudorei ◽  
Mariama C. Maiga ◽  
Zachary D. Sharp ◽  
...  

ABSTRACTOne of the major hurdles in treating tuberculosis (TB) is the time-consuming and difficult methodology for diagnosis. Stable-isotope breath tests hold great potential for rapidly diagnosing an infectious disease, monitoring therapy, and determining a bacterial phenotype in a rapid, point-of-care manner that does not require invasive sampling. Here we describe the preclinical development of a potentially highly selective TB diagnostic breath test based upon the organism’s CO dehydrogenase activity. After development of the testin vitro, we were able to use the breath test to discriminate between infected and control rabbits, demonstrating that a diagnosis can potentially be made and also that a complex bacterial phenotype can be noninvasively and rapidly studied in the host.IMPORTANCETuberculosis (TB) remains a major infectious cause of disease and death worldwide, and effective diagnosis and then treatment are the tools with which we fight TB. The more quickly and more specific the diagnosis can be made, the better, and this is also true of diagnosis being as close to the patient (point of care) as possible. Here we report our preclinical development of breath tests based upon specific mycobacterial metabolism that could, with development, allow rapid point-of-care diagnosis through measuring the mycobacterial conversion of labeled CO to labeled CO2.


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