A New Approach for On-Demand Generation of Various Oxygen Tensions for In Vitro Hypoxia Models
The development of in vitro disease models closely mimicking the functions of human disease has captured increasing attention in recent years. Oxygen tensions and gradients play essential roles in modulating biological systems in both physiologic and pathologic events. Thus, controlling oxygen tensi...
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description | The development of in vitro disease models closely mimicking the functions of human disease has captured increasing attention in recent years. Oxygen tensions and gradients play essential roles in modulating biological systems in both physiologic and pathologic events. Thus, controlling oxygen tension is critical for mimicking physiologically relevant in vivo environments for cell, tissue and organ research. We present a new approach for on-demand generation of various oxygen tensions for in vitro hypoxia models. Proof-of-concept prototypes have been developed for conventional cell culture microplate by immobilizing a novel oxygen-consuming biomaterial on the 3D-printed insert. For the first time, rapid (~3.8 minutes to reach 0.5% O2 from 20.9% O2) and precisely controlled oxygen tensions/gradients (2.68 mmHg per 50 μm distance) were generated by exposing the biocompatible biomaterial to the different depth of cell culture media. In addition, changing the position of 3D-printed inserts with immobilized biomaterials relative to the cultured cells resulted in controllable and rapid changes in oxygen tensions ( |
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Oxygen tensions and gradients play essential roles in modulating biological systems in both physiologic and pathologic events. Thus, controlling oxygen tension is critical for mimicking physiologically relevant in vivo environments for cell, tissue and organ research. We present a new approach for on-demand generation of various oxygen tensions for in vitro hypoxia models. Proof-of-concept prototypes have been developed for conventional cell culture microplate by immobilizing a novel oxygen-consuming biomaterial on the 3D-printed insert. For the first time, rapid (~3.8 minutes to reach 0.5% O2 from 20.9% O2) and precisely controlled oxygen tensions/gradients (2.68 mmHg per 50 μm distance) were generated by exposing the biocompatible biomaterial to the different depth of cell culture media. In addition, changing the position of 3D-printed inserts with immobilized biomaterials relative to the cultured cells resulted in controllable and rapid changes in oxygen tensions (<130 seconds). Compared to the current technologies, our approach allows enhanced spatiotemporal resolution and accuracy of the oxygen tensions. Additionally, it does not interfere with the testing environment while maintaining ease of use. The elegance of oxygen tension manipulation introduced by our new approach will drastically improve control and lower the technological barrier of entry for hypoxia studies. Since the biomaterials can be immobilized in any devices, including microfluidic devices and 3D-printed tissues or organs, it will serve as the basis for a new generation of experimental models previously impossible or very difficult to implement.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0155921</identifier><identifier>PMID: 27219067</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>3-D printers ; Animals ; Anoxia ; Apoptosis ; Biocompatibility ; Biocompatible Materials - chemistry ; Biology and Life Sciences ; Biomaterials ; Biomedical materials ; Cell culture ; Cell Culture Techniques - instrumentation ; Cells, Cultured ; Culture media ; Disease ; Enzymes ; Glucose ; Hydrogen peroxide ; Hypoxia ; Hypoxia - metabolism ; In Vitro Techniques ; In vivo methods and tests ; Inserts ; Ischemia ; Lab-On-A-Chip Devices ; Laboratories ; Macrophages - cytology ; Macrophages - metabolism ; Media (culture) ; Medical research ; Medicine ; Medicine and Health Sciences ; Microfluidics ; Mimicry ; Models, Biological ; Neurosurgery ; Organs ; Oxygen ; Oxygen - metabolism ; Oxygen tension ; Physical Sciences ; Physiological aspects ; Printing, Three-Dimensional ; Prototypes ; Rats ; Research and Analysis Methods ; Rodents ; Stability ; Stem cells ; Tension ; Three dimensional printing ; Tumor necrosis factor-TNF</subject><ispartof>PloS one, 2016-05, Vol.11 (5), p.e0155921-e0155921</ispartof><rights>COPYRIGHT 2016 Public Library of Science</rights><rights>2016 Li et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2016 Li et al 2016 Li et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-de8db1af673f49a1ad7972e8e2df202493cd0e7701626e8eddf0ada34405ff093</citedby><cites>FETCH-LOGICAL-c692t-de8db1af673f49a1ad7972e8e2df202493cd0e7701626e8eddf0ada34405ff093</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4878792/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4878792/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2100,2919,23857,27915,27916,53782,53784,79361,79362</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27219067$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Zhao, Feng</contributor><creatorcontrib>Li, Chunyan</creatorcontrib><creatorcontrib>Chaung, Wayne</creatorcontrib><creatorcontrib>Mozayan, Cameron</creatorcontrib><creatorcontrib>Chabra, Ranjeev</creatorcontrib><creatorcontrib>Wang, Ping</creatorcontrib><creatorcontrib>Narayan, Raj K</creatorcontrib><title>A New Approach for On-Demand Generation of Various Oxygen Tensions for In Vitro Hypoxia Models</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>The development of in vitro disease models closely mimicking the functions of human disease has captured increasing attention in recent years. Oxygen tensions and gradients play essential roles in modulating biological systems in both physiologic and pathologic events. Thus, controlling oxygen tension is critical for mimicking physiologically relevant in vivo environments for cell, tissue and organ research. We present a new approach for on-demand generation of various oxygen tensions for in vitro hypoxia models. Proof-of-concept prototypes have been developed for conventional cell culture microplate by immobilizing a novel oxygen-consuming biomaterial on the 3D-printed insert. For the first time, rapid (~3.8 minutes to reach 0.5% O2 from 20.9% O2) and precisely controlled oxygen tensions/gradients (2.68 mmHg per 50 μm distance) were generated by exposing the biocompatible biomaterial to the different depth of cell culture media. In addition, changing the position of 3D-printed inserts with immobilized biomaterials relative to the cultured cells resulted in controllable and rapid changes in oxygen tensions (<130 seconds). Compared to the current technologies, our approach allows enhanced spatiotemporal resolution and accuracy of the oxygen tensions. Additionally, it does not interfere with the testing environment while maintaining ease of use. The elegance of oxygen tension manipulation introduced by our new approach will drastically improve control and lower the technological barrier of entry for hypoxia studies. Since the biomaterials can be immobilized in any devices, including microfluidic devices and 3D-printed tissues or organs, it will serve as the basis for a new generation of experimental models previously impossible or very difficult to implement.</description><subject>3-D printers</subject><subject>Animals</subject><subject>Anoxia</subject><subject>Apoptosis</subject><subject>Biocompatibility</subject><subject>Biocompatible Materials - chemistry</subject><subject>Biology and Life Sciences</subject><subject>Biomaterials</subject><subject>Biomedical materials</subject><subject>Cell culture</subject><subject>Cell Culture Techniques - instrumentation</subject><subject>Cells, Cultured</subject><subject>Culture media</subject><subject>Disease</subject><subject>Enzymes</subject><subject>Glucose</subject><subject>Hydrogen peroxide</subject><subject>Hypoxia</subject><subject>Hypoxia - metabolism</subject><subject>In Vitro Techniques</subject><subject>In vivo methods and tests</subject><subject>Inserts</subject><subject>Ischemia</subject><subject>Lab-On-A-Chip Devices</subject><subject>Laboratories</subject><subject>Macrophages - cytology</subject><subject>Macrophages - metabolism</subject><subject>Media (culture)</subject><subject>Medical research</subject><subject>Medicine</subject><subject>Medicine and Health Sciences</subject><subject>Microfluidics</subject><subject>Mimicry</subject><subject>Models, Biological</subject><subject>Neurosurgery</subject><subject>Organs</subject><subject>Oxygen</subject><subject>Oxygen - metabolism</subject><subject>Oxygen tension</subject><subject>Physical Sciences</subject><subject>Physiological aspects</subject><subject>Printing, Three-Dimensional</subject><subject>Prototypes</subject><subject>Rats</subject><subject>Research and Analysis Methods</subject><subject>Rodents</subject><subject>Stability</subject><subject>Stem cells</subject><subject>Tension</subject><subject>Three dimensional printing</subject><subject>Tumor necrosis factor-TNF</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqNk11v0zAUhiMEYmPwDxBYQkJw0eKPxI5vJlUDtkqDSjB6ieXGdusqtYudQPvvcdZsatAuUC4cHT_ve-zjc7LsJYJjRBj6sPZtcLIeb73TY4iKgmP0KDtFnOARxZA8Pvo_yZ7FuIawICWlT7MTzDDikLLT7OcEfNV_wGS7DV5WK2B8ADM3-qg30ilwqZ0OsrHeAW_AXAbr2whmu_1SO3CjXUw78VYzdWBum-DB1X7rd1aCL17pOj7PnhhZR_2iX8-yH58_3Vxcja5nl9OLyfWoohw3I6VLtUDSUEZMziWSinGGdamxMhjinJNKQc0YRBTTFFbKQKkkyXNYGAM5OcteH3y3tY-iL00UiHHIKaEYJWJ6IJSXa7ENdiPDXnhpxW3Ah6WQobFVrQVjissClaXKcU75gitGeVFSAxfJiuHkdd5naxcbrSrtmiDrgelwx9mVWPrfIi9ZyXhn8K43CP5Xq2MjNjZWuq6l06nC3bkRIyhlS-ibf9CHb9dTS5kuYJ3xKW_VmYpJXhBS8JLARI0foNKn9MZWqY-MTfGB4P1AkJhG75qlbGMU0-_f_p-dzYfs2yN2pWXdrKKv267T4hDMD2AVfIxBm_siIyi6MbirhujGQPRjkGSvjh_oXnTX9-QvoewApQ</recordid><startdate>20160524</startdate><enddate>20160524</enddate><creator>Li, Chunyan</creator><creator>Chaung, Wayne</creator><creator>Mozayan, Cameron</creator><creator>Chabra, Ranjeev</creator><creator>Wang, Ping</creator><creator>Narayan, Raj K</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20160524</creationdate><title>A New Approach for On-Demand Generation of Various Oxygen Tensions for In Vitro Hypoxia Models</title><author>Li, Chunyan ; Chaung, Wayne ; Mozayan, Cameron ; Chabra, Ranjeev ; Wang, Ping ; Narayan, Raj K</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-de8db1af673f49a1ad7972e8e2df202493cd0e7701626e8eddf0ada34405ff093</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>3-D printers</topic><topic>Animals</topic><topic>Anoxia</topic><topic>Apoptosis</topic><topic>Biocompatibility</topic><topic>Biocompatible Materials - chemistry</topic><topic>Biology and Life Sciences</topic><topic>Biomaterials</topic><topic>Biomedical materials</topic><topic>Cell culture</topic><topic>Cell Culture Techniques - instrumentation</topic><topic>Cells, Cultured</topic><topic>Culture media</topic><topic>Disease</topic><topic>Enzymes</topic><topic>Glucose</topic><topic>Hydrogen peroxide</topic><topic>Hypoxia</topic><topic>Hypoxia - metabolism</topic><topic>In Vitro Techniques</topic><topic>In vivo methods and tests</topic><topic>Inserts</topic><topic>Ischemia</topic><topic>Lab-On-A-Chip Devices</topic><topic>Laboratories</topic><topic>Macrophages - cytology</topic><topic>Macrophages - metabolism</topic><topic>Media (culture)</topic><topic>Medical research</topic><topic>Medicine</topic><topic>Medicine and Health Sciences</topic><topic>Microfluidics</topic><topic>Mimicry</topic><topic>Models, Biological</topic><topic>Neurosurgery</topic><topic>Organs</topic><topic>Oxygen</topic><topic>Oxygen - metabolism</topic><topic>Oxygen tension</topic><topic>Physical Sciences</topic><topic>Physiological aspects</topic><topic>Printing, Three-Dimensional</topic><topic>Prototypes</topic><topic>Rats</topic><topic>Research and Analysis Methods</topic><topic>Rodents</topic><topic>Stability</topic><topic>Stem cells</topic><topic>Tension</topic><topic>Three dimensional printing</topic><topic>Tumor necrosis factor-TNF</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Li, Chunyan</creatorcontrib><creatorcontrib>Chaung, Wayne</creatorcontrib><creatorcontrib>Mozayan, Cameron</creatorcontrib><creatorcontrib>Chabra, Ranjeev</creatorcontrib><creatorcontrib>Wang, Ping</creatorcontrib><creatorcontrib>Narayan, Raj K</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Li, Chunyan</au><au>Chaung, Wayne</au><au>Mozayan, Cameron</au><au>Chabra, Ranjeev</au><au>Wang, Ping</au><au>Narayan, Raj K</au><au>Zhao, Feng</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A New Approach for On-Demand Generation of Various Oxygen Tensions for In Vitro Hypoxia Models</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2016-05-24</date><risdate>2016</risdate><volume>11</volume><issue>5</issue><spage>e0155921</spage><epage>e0155921</epage><pages>e0155921-e0155921</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>The development of in vitro disease models closely mimicking the functions of human disease has captured increasing attention in recent years. Oxygen tensions and gradients play essential roles in modulating biological systems in both physiologic and pathologic events. Thus, controlling oxygen tension is critical for mimicking physiologically relevant in vivo environments for cell, tissue and organ research. We present a new approach for on-demand generation of various oxygen tensions for in vitro hypoxia models. Proof-of-concept prototypes have been developed for conventional cell culture microplate by immobilizing a novel oxygen-consuming biomaterial on the 3D-printed insert. For the first time, rapid (~3.8 minutes to reach 0.5% O2 from 20.9% O2) and precisely controlled oxygen tensions/gradients (2.68 mmHg per 50 μm distance) were generated by exposing the biocompatible biomaterial to the different depth of cell culture media. In addition, changing the position of 3D-printed inserts with immobilized biomaterials relative to the cultured cells resulted in controllable and rapid changes in oxygen tensions (<130 seconds). Compared to the current technologies, our approach allows enhanced spatiotemporal resolution and accuracy of the oxygen tensions. Additionally, it does not interfere with the testing environment while maintaining ease of use. The elegance of oxygen tension manipulation introduced by our new approach will drastically improve control and lower the technological barrier of entry for hypoxia studies. Since the biomaterials can be immobilized in any devices, including microfluidic devices and 3D-printed tissues or organs, it will serve as the basis for a new generation of experimental models previously impossible or very difficult to implement.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>27219067</pmid><doi>10.1371/journal.pone.0155921</doi><oa>free_for_read</oa></addata></record> |
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subjects | 3-D printers Animals Anoxia Apoptosis Biocompatibility Biocompatible Materials - chemistry Biology and Life Sciences Biomaterials Biomedical materials Cell culture Cell Culture Techniques - instrumentation Cells, Cultured Culture media Disease Enzymes Glucose Hydrogen peroxide Hypoxia Hypoxia - metabolism In Vitro Techniques In vivo methods and tests Inserts Ischemia Lab-On-A-Chip Devices Laboratories Macrophages - cytology Macrophages - metabolism Media (culture) Medical research Medicine Medicine and Health Sciences Microfluidics Mimicry Models, Biological Neurosurgery Organs Oxygen Oxygen - metabolism Oxygen tension Physical Sciences Physiological aspects Printing, Three-Dimensional Prototypes Rats Research and Analysis Methods Rodents Stability Stem cells Tension Three dimensional printing Tumor necrosis factor-TNF |
title | A New Approach for On-Demand Generation of Various Oxygen Tensions for In Vitro Hypoxia Models |
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