12 results on '"Collin Edington"'
Search Results
2. Quantitative Label-Free Imaging of 3D Vascular Networks Self-Assembled in Synthetic Hydrogels
- Author
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Elizabeth E. Torr, William L. Murphy, Daniel A. Gil, Melissa C. Skala, Linda G. Griffith, Peyton Uhl, Gaurav Kaushik, William T. Daly, James A. Thomson, Collin Edington, Cheryl M. Soref, Gianluca Fontana, Michael P. Schwartz, Elizabeth S. Berge, Jessica Antosiewicz-Bourget, and Massachusetts Institute of Technology. Department of Biological Engineering
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Biomedical Engineering ,Cell Culture Techniques ,Pharmaceutical Science ,Neovascularization, Physiologic ,Image processing ,02 engineering and technology ,010402 general chemistry ,01 natural sciences ,Article ,Self assembled ,Polyethylene Glycols ,Biomaterials ,Bioreactors ,Imaging, Three-Dimensional ,Bioreactor ,Humans ,Label free ,Recirculating flow ,Microscopy, Confocal ,Chemistry ,Endothelial Cells ,Hydrogels ,021001 nanoscience & nanotechnology ,NAD ,0104 chemical sciences ,Platelet Endothelial Cell Adhesion Molecule-1 ,Autofluorescence ,Multiphoton fluorescence microscope ,Microscopy, Fluorescence, Multiphoton ,Self-healing hydrogels ,Blood Vessels ,0210 nano-technology ,Pericytes ,NADP ,Biomedical engineering - Abstract
Vascularization is an important strategy to overcome diffusion limits and enable the formation of complex, physiologically relevant engineered tissues and organoids. Self-assembly is a technique to generate in vitro vascular networks, but engineering the necessary network morphology and function remains challenging. Here, autofluorescence multiphoton microscopy (aMPM), a label-free imaging technique, is used to quantitatively evaluate in vitro vascular network morphology. Vascular networks are generated using human embryonic stem cell–derived endothelial cells and primary human pericytes encapsulated in synthetic poly(ethylene glycol)-based hydrogels. Two custom-built bioreactors are used to generate distinct fluid flow patterns during vascular network formation: recirculating flow or continuous flow. aMPM is used to image these 3D vascular networks without the need for fixation, labels, or dyes. Image processing and analysis algorithms are developed to extract quantitative morphological parameters from these label-free images. It is observed with aMPM that both bioreactors promote formation of vascular networks with lower network anisotropy compared to static conditions, and the continuous flow bioreactor induces more branch points compared to static conditions. Importantly, these results agree with trends observed with immunocytochemistry. These studies demonstrate that aMPM allows label-free monitoring of vascular network morphology to streamline optimization of growth conditions and provide quality control of engineered tissues., National Institutes of Health (U.S.) (Grant R01 HL093282-01A1), National Institutes of Health (U.S.) (Grant 1U H2TR000506-01), National Institutes of Health (U.S.) (Grant 3UH2TR000506-02S1), National Institutes of Health (U.S.) (Grant 4U H3TR000506-03), National Institutes of Health (U.S.) (Grant R01CA205101), National Institutes of Health (U.S.) (Grant R01CA185747), National Institutes of Health (U.S.) (Grant R01CA211082), National Institutes of Health (U.S.) (Grant R01CA226526), National Science Foundation (U.S.) (Grant (CBET-1642287), Entertainment Industry Foundation. Stand Up to Cancer Colorectal Cancer Dream Team (Grant SU2C-AACR-IG-08-16), Stand Up To Cancer (Grant SU2C-AACR-IG-08-16)
- Published
- 2018
3. Autofluorescence multiphoton microscopy for quality control of human vascular tissue constructs (Conference Presentation)
- Author
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William T. Daly, Michael P. Schwartz, Daniel A. Gil, Elizabeth S. Berge, Jessica Antosiewicz-Bourget, Collin Edington, Melissa C. Skala, Cheryl M. Soref, Gianluca Fontana, Gaurav Kaushik, Peyton Uhl, Elizabeth E. Torr, William L. Murphy, James A. Thomson, and Linda G. Griffith
- Subjects
Autofluorescence ,Tissue engineering ,Tight junction ,Chemistry ,Self-healing hydrogels ,Immunohistochemistry ,Stem cell ,Vascular tissue ,Immunostaining ,Biomedical engineering - Abstract
Engineered tissues offer great promise as engrafted therapies and in vitro models, but these tissues require a vascular network to retain viability at large scales. Significant efforts are focused on optimizing these in vitro vascular constructs, yet current evaluation methods require fixation and immunostaining. These destructive evaluation methods alter vascular network morphology, and cannot non-invasively monitor vascular assembly over time. Here, we demonstrate that autofluorescence multiphoton microscopy (MPM) can quantitatively assess the morphology of living 3D vascular networks without fixation, labels, or dyes. Autofluorescence MPM was used to non-invasively monitor the effect of culture conditions on 3D vascular network formation. Human embryonic stem (ES) cell-derived endothelial cells and primary human pericytes cultured in polyethylene glycol (PEG) hydrogels self-assembled into 3D vascular networks. Autofluorescence MPM of the metabolic co-enzyme NAD(P)H (excitation/emission wavelengths of 750 nm/400-460 nm) was used to quantify morphological parameters at day 6 of culture. Specifically, vessel diameter, vascular density, branch point density, and integration of endothelial cells into the network were quantified. Dynamic culture conditions (flow at 1μL/sec) led to vascular networks with higher mean vessel diameter compared to static culture (p
- Published
- 2018
4. Integrated gut/liver microphysiological systems elucidates inflammatory inter-tissue crosstalk
- Author
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Wen L.K. Chen, Collin Edington, Emily Suter, Jiajie Yu, Jeremy J. Velazquez, Jason G. Velazquez, Michael Shockley, Emma M. Large, Raman Venkataramanan, David J. Hughes, Cynthia L. Stokes, David L. Trumper, Rebecca L. Carrier, Murat Cirit, Linda G. Griffith, Douglas A. Lauffenburger, Institute for Medical Engineering and Science, Harvard University--MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology. Department of Biological Engineering, Massachusetts Institute of Technology. Department of Biology, Massachusetts Institute of Technology. Department of Chemical Engineering, Massachusetts Institute of Technology. Department of Materials Science and Engineering, Massachusetts Institute of Technology. Department of Mechanical Engineering, Chen, Wen Li, Edington, Collin D, Suter, Emily C, Yu, Jiajie, Velazquez, Jeremy J., Velazquez, Jason G, Shockley, Michael J, Trumper, David L, Carrier, Rebecca, Cirit, Murat, Griffith, Linda G, and Lauffenburger, Douglas A
- Subjects
0301 basic medicine ,Cell signaling ,Chemokine ,Colon ,Kupffer Cells ,medicine.medical_treatment ,Bioengineering ,Inflammation ,Cell Communication ,Biology ,Applied Microbiology and Biotechnology ,Article ,Systems Biotechnology ,sepsis ,03 medical and health sciences ,gut‐liver interaction ,Downregulation and upregulation ,Lab-On-A-Chip Devices ,medicine ,Humans ,Immunologic Factors ,organ‐on‐a‐chip ,microphysiological system ,Cells, Cultured ,Immunoassay ,Miniaturization ,CXCR3 ligands ,FGF19 ,Articles ,Equipment Design ,Coculture Techniques ,Cell biology ,Equipment Failure Analysis ,Systems Integration ,Crosstalk (biology) ,030104 developmental biology ,Cytokine ,Liver ,Immunology ,Hepatocytes ,biology.protein ,Cytokines ,CXCL9 ,Caco-2 Cells ,medicine.symptom ,Biotechnology - Abstract
A capability for analyzing complex cellular communication among tissues is important in drug discovery and development, and in vitro technologies for doing so are required for human applications. A prominent instance is communication between the gut and the liver, whereby perturbations of one tissue can influence behavior of the other. Here, we present a study on human gut-liver tissue interactions under normal and inflammatory contexts, via an integrative multi-organ platform comprising human liver (hepatocytes and Kupffer cells), and intestinal (enterocytes, goblet cells, and dendritic cells) models. Our results demonstrated long-term (>2 weeks) maintenance of intestinal (e.g., barrier integrity) and hepatic (e.g., albumin) functions in baseline interaction. Gene expression data comparing liver in interaction with gut, versus isolation, revealed modulation of bile acid metabolism. Intestinal FGF19 secretion and associated inhibition of hepatic CYP7A1 expression provided evidence of physiologically relevant gut-liver crosstalk. Moreover, significant non-linear modulation of cytokine responses was observed under inflammatory gut-liver interaction; for example, production of CXCR3 ligands (CXCL9,10,11) was synergistically enhanced. RNA-seq analysis revealed significant upregulation of IFNα/β/γ signaling during inflammatory gut-liver crosstalk, with these pathways implicated in the synergistic CXCR3 chemokine production. Exacerbated inflammatory response in gut-liver interaction also negatively affected tissue-specific functions (e.g., liver metabolism). These findings illustrate how an integrated multi-tissue platform can generate insights useful for understanding complex pathophysiological processes such as inflammatory organ crosstalk., National Institutes of Health (U.S.) (grant UH3TR00069), United States. Defense Advanced Research Projects Agency (grant Microphysiological Systems Program (W911NF-12-2-00))
- Published
- 2017
5. Integrated Gut and Liver Microphysiological Systems for Quantitative In Vitro Pharmacokinetic Studies
- Author
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Linda G. Griffith, Nikolaos Tsamandouras, Cynthia L. Stokes, Wen Li Kelly Chen, Murat Cirit, Collin Edington, Massachusetts Institute of Technology. Department of Biological Engineering, Tsamandouras, Nikolaos, Chen, Wen Li, Edington, Collin D, Griffith, Linda G, and Cirit, Murat
- Subjects
0301 basic medicine ,Diclofenac ,Hydrocortisone ,Pharmacology toxicology ,Pharmaceutical Science ,02 engineering and technology ,Computational biology ,Biology ,Pharmacology ,In Vitro Techniques ,Article ,03 medical and health sciences ,Pharmacokinetics ,medicine ,Humans ,Intestinal Mucosa ,Intestinal permeability ,Robustness (evolution) ,021001 nanoscience & nanotechnology ,medicine.disease ,In vitro ,030104 developmental biology ,Drug development ,Liver ,0210 nano-technology ,Drug metabolism ,Oral retinoid - Abstract
Investigation of the pharmacokinetics (PK) of a compound is of significant importance during the early stages of drug development, and therefore several in vitro systems are routinely employed for this purpose. However, the need for more physiologically realistic in vitro models has recently fueled the emerging field of tissue-engineered 3D cultures, also referred to as organs-on-chips, or microphysiological systems (MPSs). We have developed a novel fluidic platform that interconnects multiple MPSs, allowing PK studies in multi-organ in vitro systems along with the collection of high-content quantitative data. This platform was employed here to integrate a gut and a liver MPS together in continuous communication, and investigate simultaneously different PK processes taking place after oral drug administration in humans (e.g., intestinal permeability, hepatic metabolism). Measurement of tissue-specific phenotypic metrics indicated that gut and liver MPSs can be fluidically coupled with circulating common medium without compromising their functionality. The PK of diclofenac and hydrocortisone was investigated under different experimental perturbations, and results illustrate the robustness of this integrated system for quantitative PK studies. Mechanistic model-based analysis of the obtained data allowed the derivation of the intrinsic parameters (e.g., permeability, metabolic clearance) associated with the PK processes taking place in each MPS. Although these processes were not substantially affected by the gut-liver interaction, our results indicate that inter-MPS communication can have a modulating effect (hepatic metabolism upregulation). We envision that our integrative approach, which combines multi-cellular tissue models, multi-MPS platforms, and quantitative mechanistic modeling, will have broad applicability in pre-clinical drug development., United States. Defense Advanced Research Projects Agency (Grant W911NF-12-2-0039), National Institutes of Health (U.S.) (Grant 4-UH3-TR000496-03)
- Published
- 2017
6. Integration of systems biology with organs-on-chips to humanize therapeutic development
- Author
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Murat Cirit, Linda G. Griffith, Alan Wells, Amanda M. Clark, David L. Trumper, Wen Li Kelly Chen, and Collin Edington
- Subjects
0301 basic medicine ,Tissue engineered ,Computer science ,Scale (chemistry) ,Systems biology ,Nanotechnology ,Data science ,Living systems ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Human disease ,Drug development ,030220 oncology & carcinogenesis ,Tissue Chip ,Organ system - Abstract
“Mice are not little people” – a refrain becoming louder as the gaps between animal models and human disease become more apparent. At the same time, three emerging approaches are headed toward integration: powerful systems biology analysis of cell-cell and intracellular signaling networks in patient-derived samples; 3D tissue engineered models of human organ systems, often made from stem cells; and micro-fluidic and meso-fluidic devices that enable living systems to be sustained, perturbed and analyzed for weeks in culture. Integration of these rapidly moving fields has the potential to revolutionize development of therapeutics for complex, chronic diseases, including those that have weak genetic bases and substantial contributions from gene-environment interactions. Technical challenges in modeling complex diseases with “organs on chips” approaches include the need for relatively large tissue masses and organ-organ cross talk to capture systemic effects, such that current microfluidic formats often fail to capture the required scale and complexity for interconnected systems. These constraints drive development of new strategies for designing in vitro models, including perfusing organ models, as well as “mesofluidic” pumping and circulation in platforms connecting several organ systems, to achieve the appropriate physiological relevance.
- Published
- 2017
7. Vascular Networks: Quantitative Label-Free Imaging of 3D Vascular Networks Self-Assembled in Synthetic Hydrogels (Adv. Healthcare Mater. 2/2019)
- Author
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William T. Daly, James A. Thomson, Gaurav Kaushik, Jessica Antosiewicz-Bourget, Linda G. Griffith, Melissa C. Skala, Elizabeth S. Berge, Peyton Uhl, Daniel A. Gil, Elizabeth E. Torr, William L. Murphy, Michael P. Schwartz, Cheryl M. Soref, Collin Edington, and Gianluca Fontana
- Subjects
Biomaterials ,Autofluorescence ,Poly ethylene glycol ,Multiphoton fluorescence microscope ,Materials science ,Self-healing hydrogels ,Biomedical Engineering ,Pharmaceutical Science ,Nanotechnology ,Self-assembly ,Self assembled ,Label free - Published
- 2019
8. Tailoring the Trajectory of Cell Rolling with Cytotactic Surfaces
- Author
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Zvi Liron, Carsen Kline, Sungeun Eom, Anna C. Balazs, Richard R. Koepsel, Collin Edington, Takeo Kanade, German V. Kolmakov, Hironobu Murata, Alan J. Russell, Daniel McKeel, and Jill D. Andersen
- Subjects
Medical diagnostic ,Materials science ,Microfluidics ,HL-60 Cells ,Nanotechnology ,Cell Separation ,Cell Movement ,Cell Adhesion ,Electrochemistry ,Cell separation ,Humans ,General Materials Science ,Sulfhydryl Compounds ,Spectroscopy ,Staining and Labeling ,Cell adhesion molecule ,Fatty Acids ,Sorting ,Surfaces and Interfaces ,Adhesion ,Flow Cytometry ,Condensed Matter Physics ,Carbodiimides ,P-Selectin ,Cell Tracking ,Trajectory ,Glass ,Gold ,Dimethylamines ,Chemical labeling - Abstract
Cell separation technology is a key tool for biological studies and medical diagnostics that relies primarily on chemical labeling to identify particular phenotypes. An emergent method of sorting cells based on differential rolling on chemically patterned substrates holds potential benefits over existing technologies, but the underlying mechanisms being exploited are not well characterized. In order to better understand cell rolling on complex surfaces, a microfluidic device with chemically patterned stripes of the cell adhesion molecule P-selectin was designed. The behavior of HL-60 cells rolling under flow was analyzed using a high-resolution visual tracking system. This behavior was then correlated to a number of established predictive models. The combination of computational modeling and widely available fabrication techniques described herein represents a crucial step toward the successful development of continuous, label-free methods of cell separation based on rolling adhesion.
- Published
- 2011
9. Engineering of cell membranes with a bisphosphonate-containing polymer using ATRP synthesis for bone targeting
- Author
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Collin Edington, Moncy V. Jose, Richard R. Koepsel, Jill D. Andersen, Sholpan Askarova, Hironobu Murata, Sonia D'Souza, Alan J. Russell, William P. Clafshenkel, and Yuliya Yantsen
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Materials science ,Polymers ,Surface Properties ,Biophysics ,Succinimides ,Bioengineering ,HL-60 Cells ,Bone and Bones ,Polymerization ,Biomaterials ,Rats, Sprague-Dawley ,Polymer chemistry ,Side chain ,Animals ,Humans ,Cell Proliferation ,chemistry.chemical_classification ,Diphosphonates ,Tissue Engineering ,Atom-transfer radical-polymerization ,Mesenchymal stem cell ,Cell Membrane ,Cell Differentiation ,Mesenchymal Stem Cells ,Adhesion ,Polymer ,Hydrogen-Ion Concentration ,Rats ,Membrane ,chemistry ,Mechanics of Materials ,Cell culture ,Covalent bond ,Ceramics and Composites - Abstract
The field of polymer-based membrane engineering has expanded since we first demonstrated the reaction of N-hydroxysuccinimide ester-terminated polymers with cells and tissues almost two decades ago. One remaining obstacle, especially for conjugation of polymers to cells, has been that exquisite control over polymer structure and functionality has not been used to influence the behavior of cells. Herein, we describe a multifunctional atom transfer radical polymerization initiator and its use to synthesize water-soluble polymers that are modified with bisphosphonate side chains and then covalently bound to the surface of live cells. The polymers contained between 1.7 and 3.1 bisphosphonates per chain and were shown to bind to hydroxyapatite crystals with kinetics similar to free bisphosphonate binding. We engineered the membranes of both HL-60 cells and mesenchymal stem cells in order to impart polymer-guided bone adhesion properties on the cells. Covalent coupling of the polymer to the non-adherent HL-60 cell line or mesenchymal stem cells was non-toxic by proliferation assays and enhanced the binding of these cells to bone.
- Published
- 2014
10. Electrochemical impedance spectroscopy to assess vascular oxidative stress
- Author
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Mark L. Barr, Rongsong Li, Eun Sok Kim, Collin Edington, Lisong Ai, Hongyu Yu, Tzung K. Hsiai, and Fei Yu
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Aortic arch ,Biomedical Engineering ,Analytical chemistry ,medicine.disease_cause ,Article ,Lesion ,medicine.artery ,medicine ,Animals ,Humans ,Computer Simulation ,Aorta ,Reproducibility ,Chemistry ,Models, Cardiovascular ,Atherosclerosis ,Dielectric spectroscopy ,Microelectrode ,Oxidative Stress ,Dielectric Spectroscopy ,Electrode ,Rabbits ,medicine.symptom ,Oxidative stress ,Biomedical engineering - Abstract
Vascular inflammatory responses are intimately linked with oxidative stress, favoring the development of pre-atherosclerotic lesions. We proposed that oxidized low density lipoprotein (oxLDL) and foam cell infiltrates in the subendothelial layer engendered distinct electrochemical properties that could be measured in terms of the electrochemical impedance spectroscopy (EIS). Concentric bipolar microelectrodes were applied to interrogate EIS of aortas isolated from fat-fed New Zealand White (NZW) rabbits and explants of human aortas. Frequency-dependent EIS measurements were assessed between 10 kHz and 100 kHz, and were significantly elevated in the pre-atherosclerotic lesions in which oxLDL and macrophage infiltrates were prevalent (At 100 kHz: aortic arch lesion = 26.7 ± 2.7 kΩ vs. control = 15.8 ± 2.4 kΩ; at 10 kHz: lesions = 49.2 ± 7.3 kΩ vs. control = 27.6 ± 2.7 kΩ, n = 10, p
- Published
- 2010
11. Detection of vascular oxidative stress in atherosclerotic lesions by electrochemical impedance spectroscopy
- Author
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Collin Edington, Lisong Ai, Eun Sok Kim, Fei Yu, and Tzung K. Hsiai
- Subjects
Chemistry ,Genetics ,medicine ,Biophysics ,medicine.disease_cause ,Molecular Biology ,Biochemistry ,Oxidative stress ,Biotechnology ,Dielectric spectroscopy - Published
- 2010
12. Tailoring the Trajectory of Cell Rolling with Cytotactic Surfaces.
- Author
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Collin Edington, Hironobu Murata, Richard Koepsel, Jill Andersen, Sungeun Eom, Takeo Kanade, Anna C. Balazs, German Kolmakov, Carsen Kline, Daniel McKeel, Zvi Liron, and Alan J. Russell
- Subjects
- *
CELL membranes , *SEPARATION (Technology) , *PHENOTYPES , *MICROFLUIDIC devices , *PREDICTION models , *CYTOMETRY ,CHEMICAL labeling - Abstract
Cell separation technology is a key tool for biological studies and medical diagnostics that relies primarily on chemical labeling to identify particular phenotypes. An emergent method of sorting cells based on differential rolling on chemically patterned substrates holds potential benefits over existing technologies, but the underlying mechanisms being exploited are not well characterized. In order to better understand cell rolling on complex surfaces, a microfluidic device with chemically patterned stripes of the cell adhesion molecule P-selectin was designed. The behavior of HL-60 cells rolling under flow was analyzed using a high-resolution visual tracking system. This behavior was then correlated to a number of established predictive models. The combination of computational modeling and widely available fabrication techniques described herein represents a crucial step toward the successful development of continuous, label-free methods of cell separation based on rolling adhesion. [ABSTRACT FROM AUTHOR]
- Published
- 2011
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