A microfabricated array bioreactor for perfused 3D liver culture
We describe the design, fabrication, and performance of a bioreactor that enables both morphogenesis of 3D tissue structures under continuous perfusion and repeated in situ observation by light microscopy. Three‐dimensional scaffolds were created by deep reactive ion etching of silicon wafers to cre...
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Veröffentlicht in: | Biotechnology and bioengineering 2002-05, Vol.78 (3), p.257-269 |
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creator | Powers, Mark J. Domansky, Karel Kaazempur-Mofrad, Mohammad R. Kalezi, Artemis Capitano, Adam Upadhyaya, Arpita Kurzawski, Petra Wack, Kathryn E. Stolz, Donna Beer Kamm, Roger Griffith, Linda G. |
description | We describe the design, fabrication, and performance of a bioreactor that enables both morphogenesis of 3D tissue structures under continuous perfusion and repeated in situ observation by light microscopy. Three‐dimensional scaffolds were created by deep reactive ion etching of silicon wafers to create an array of channels (through‐holes) with cell‐adhesive walls. Scaffolds were combined with a cell‐retaining filter and support in a reactor housing designed to deliver a continuous perfusate across the top of the array and through the 3D tissue mass in each channel. Reactor dimensions were constructed so that perfusate flow rates meet estimated values of cellular oxygen demands while providing fluid shear stress at or below a physiological range ( |
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Three‐dimensional scaffolds were created by deep reactive ion etching of silicon wafers to create an array of channels (through‐holes) with cell‐adhesive walls. Scaffolds were combined with a cell‐retaining filter and support in a reactor housing designed to deliver a continuous perfusate across the top of the array and through the 3D tissue mass in each channel. Reactor dimensions were constructed so that perfusate flow rates meet estimated values of cellular oxygen demands while providing fluid shear stress at or below a physiological range (<2 dyne cm2), as determined by comparison of numerical models of reactor fluid flow patterns to literature values of physiological shear stresses. We studied the behavior of primary rat hepatocytes seeded into the reactors and cultured for up to 2 weeks, and found that cells seeded into the channels rearranged extensively to form tissue like structures and remained viable throughout the culture period. We further observed that preaggregation of the cells into spheroidal structures prior to seeding improved the morphogenesis of tissue structure and maintenance of viability. We also demonstrate repeated in situ imaging of tissue structure and function using two‐photon microscopy. © 2002 Wiley Periodicals, Inc. Biotechnol Bioeng 78: 257–269, 2002.</description><identifier>ISSN: 0006-3592</identifier><identifier>EISSN: 1097-0290</identifier><identifier>DOI: 10.1002/bit.10143</identifier><identifier>PMID: 11920442</identifier><identifier>CODEN: BIBIAU</identifier><language>eng</language><publisher>New York: Wiley Subscription Services, Inc., A Wiley Company</publisher><subject>Animals ; Biological and medical sciences ; bioreactor ; Bioreactors ; Biotechnology ; Cell Culture Techniques ; Fundamental and applied biological sciences. Psychology ; gene delivery ; Green Fluorescent Proteins ; Hepatocytes - cytology ; Hepatocytes - physiology ; Imaging, Three-Dimensional ; liver ; Luminescent Proteins - genetics ; Luminescent Proteins - metabolism ; Male ; Methods. Procedures. Technologies ; Microscopy ; Morphogenesis - physiology ; Organ Culture Techniques - methods ; Organ Culture Techniques - trends ; Oxygen - physiology ; Perfusion ; Rats ; Space life sciences ; Stress, Mechanical ; tissue engineering ; Tissue Engineering - methods ; Tissue Engineering - trends ; Various methods and equipments</subject><ispartof>Biotechnology and bioengineering, 2002-05, Vol.78 (3), p.257-269</ispartof><rights>Copyright © 2002 Wiley Periodicals, Inc.</rights><rights>2002 INIST-CNRS</rights><rights>Copyright 2002 Wiley Periodicals, Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5253-b9596d6f2fb8575d179969d05968ee9cbee97986b212527258135aa3ebe3e4033</citedby><cites>FETCH-LOGICAL-c5253-b9596d6f2fb8575d179969d05968ee9cbee97986b212527258135aa3ebe3e4033</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fbit.10143$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fbit.10143$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,777,781,1412,27905,27906,45555,45556</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=14185404$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11920442$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Powers, Mark J.</creatorcontrib><creatorcontrib>Domansky, Karel</creatorcontrib><creatorcontrib>Kaazempur-Mofrad, Mohammad R.</creatorcontrib><creatorcontrib>Kalezi, Artemis</creatorcontrib><creatorcontrib>Capitano, Adam</creatorcontrib><creatorcontrib>Upadhyaya, Arpita</creatorcontrib><creatorcontrib>Kurzawski, Petra</creatorcontrib><creatorcontrib>Wack, Kathryn E.</creatorcontrib><creatorcontrib>Stolz, Donna Beer</creatorcontrib><creatorcontrib>Kamm, Roger</creatorcontrib><creatorcontrib>Griffith, Linda G.</creatorcontrib><title>A microfabricated array bioreactor for perfused 3D liver culture</title><title>Biotechnology and bioengineering</title><addtitle>Biotechnol. Bioeng</addtitle><description>We describe the design, fabrication, and performance of a bioreactor that enables both morphogenesis of 3D tissue structures under continuous perfusion and repeated in situ observation by light microscopy. Three‐dimensional scaffolds were created by deep reactive ion etching of silicon wafers to create an array of channels (through‐holes) with cell‐adhesive walls. Scaffolds were combined with a cell‐retaining filter and support in a reactor housing designed to deliver a continuous perfusate across the top of the array and through the 3D tissue mass in each channel. Reactor dimensions were constructed so that perfusate flow rates meet estimated values of cellular oxygen demands while providing fluid shear stress at or below a physiological range (<2 dyne cm2), as determined by comparison of numerical models of reactor fluid flow patterns to literature values of physiological shear stresses. We studied the behavior of primary rat hepatocytes seeded into the reactors and cultured for up to 2 weeks, and found that cells seeded into the channels rearranged extensively to form tissue like structures and remained viable throughout the culture period. We further observed that preaggregation of the cells into spheroidal structures prior to seeding improved the morphogenesis of tissue structure and maintenance of viability. We also demonstrate repeated in situ imaging of tissue structure and function using two‐photon microscopy. © 2002 Wiley Periodicals, Inc. Biotechnol Bioeng 78: 257–269, 2002.</description><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>bioreactor</subject><subject>Bioreactors</subject><subject>Biotechnology</subject><subject>Cell Culture Techniques</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>gene delivery</subject><subject>Green Fluorescent Proteins</subject><subject>Hepatocytes - cytology</subject><subject>Hepatocytes - physiology</subject><subject>Imaging, Three-Dimensional</subject><subject>liver</subject><subject>Luminescent Proteins - genetics</subject><subject>Luminescent Proteins - metabolism</subject><subject>Male</subject><subject>Methods. Procedures. Technologies</subject><subject>Microscopy</subject><subject>Morphogenesis - physiology</subject><subject>Organ Culture Techniques - methods</subject><subject>Organ Culture Techniques - trends</subject><subject>Oxygen - physiology</subject><subject>Perfusion</subject><subject>Rats</subject><subject>Space life sciences</subject><subject>Stress, Mechanical</subject><subject>tissue engineering</subject><subject>Tissue Engineering - methods</subject><subject>Tissue Engineering - trends</subject><subject>Various methods and equipments</subject><issn>0006-3592</issn><issn>1097-0290</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2002</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkEtPxCAQx4nR6Po4-AVML5p4qPIoUG6-11fUg8YjATpN0K5doVX324u7q56Mh2Fg5jfzD3-ENgneIxjTfeu7dCEFW0ADgpXMMVV4EQ0wxiJnXNEVtBrjU3rKUohltEKIorgo6AAdHGYj70JbGxu8Mx1UmQnBTDLr2wDGdW3I6hRjCHUfU5edZI1_g5C5vun6AOtoqTZNhI15XkMPZ6f3x-f59e3w4vjwOneccpZbxZWoRE1rW3LJKyKVEqrCqVoCKGfTIVUpLCWUU0l5SRg3hoEFBgVmbA3tzPaOQ_vaQ-z0yEcHTWNeoO2jloTzQjD8L0hKLiTBRQJ3Z2D6fowBaj0OfmTCRBOsv3zVyVc99TWxW_OlvR1B9UvOjUzA9hww0ZmmDubF-fjLFUm2mIruz7h338Dkb0V9dHH_LZ3PJnzs4ONnwoRnLSSTXD_eDHV5d8YEv7rTl-wTy5-bcw</recordid><startdate>20020505</startdate><enddate>20020505</enddate><creator>Powers, Mark J.</creator><creator>Domansky, Karel</creator><creator>Kaazempur-Mofrad, Mohammad R.</creator><creator>Kalezi, Artemis</creator><creator>Capitano, Adam</creator><creator>Upadhyaya, Arpita</creator><creator>Kurzawski, Petra</creator><creator>Wack, Kathryn E.</creator><creator>Stolz, Donna Beer</creator><creator>Kamm, Roger</creator><creator>Griffith, Linda G.</creator><general>Wiley Subscription Services, Inc., A Wiley Company</general><general>Wiley</general><scope>BSCLL</scope><scope>IQODW</scope><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>7QO</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>20020505</creationdate><title>A microfabricated array bioreactor for perfused 3D liver culture</title><author>Powers, Mark J. ; Domansky, Karel ; Kaazempur-Mofrad, Mohammad R. ; Kalezi, Artemis ; Capitano, Adam ; Upadhyaya, Arpita ; Kurzawski, Petra ; Wack, Kathryn E. ; Stolz, Donna Beer ; Kamm, Roger ; Griffith, Linda G.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5253-b9596d6f2fb8575d179969d05968ee9cbee97986b212527258135aa3ebe3e4033</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2002</creationdate><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>bioreactor</topic><topic>Bioreactors</topic><topic>Biotechnology</topic><topic>Cell Culture Techniques</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>gene delivery</topic><topic>Green Fluorescent Proteins</topic><topic>Hepatocytes - cytology</topic><topic>Hepatocytes - physiology</topic><topic>Imaging, Three-Dimensional</topic><topic>liver</topic><topic>Luminescent Proteins - genetics</topic><topic>Luminescent Proteins - metabolism</topic><topic>Male</topic><topic>Methods. Procedures. Technologies</topic><topic>Microscopy</topic><topic>Morphogenesis - physiology</topic><topic>Organ Culture Techniques - methods</topic><topic>Organ Culture Techniques - trends</topic><topic>Oxygen - physiology</topic><topic>Perfusion</topic><topic>Rats</topic><topic>Space life sciences</topic><topic>Stress, Mechanical</topic><topic>tissue engineering</topic><topic>Tissue Engineering - methods</topic><topic>Tissue Engineering - trends</topic><topic>Various methods and equipments</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Powers, Mark J.</creatorcontrib><creatorcontrib>Domansky, Karel</creatorcontrib><creatorcontrib>Kaazempur-Mofrad, Mohammad R.</creatorcontrib><creatorcontrib>Kalezi, Artemis</creatorcontrib><creatorcontrib>Capitano, Adam</creatorcontrib><creatorcontrib>Upadhyaya, Arpita</creatorcontrib><creatorcontrib>Kurzawski, Petra</creatorcontrib><creatorcontrib>Wack, Kathryn E.</creatorcontrib><creatorcontrib>Stolz, Donna Beer</creatorcontrib><creatorcontrib>Kamm, Roger</creatorcontrib><creatorcontrib>Griffith, Linda G.</creatorcontrib><collection>Istex</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Biotechnology and bioengineering</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Powers, Mark J.</au><au>Domansky, Karel</au><au>Kaazempur-Mofrad, Mohammad R.</au><au>Kalezi, Artemis</au><au>Capitano, Adam</au><au>Upadhyaya, Arpita</au><au>Kurzawski, Petra</au><au>Wack, Kathryn E.</au><au>Stolz, Donna Beer</au><au>Kamm, Roger</au><au>Griffith, Linda G.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A microfabricated array bioreactor for perfused 3D liver culture</atitle><jtitle>Biotechnology and bioengineering</jtitle><addtitle>Biotechnol. Bioeng</addtitle><date>2002-05-05</date><risdate>2002</risdate><volume>78</volume><issue>3</issue><spage>257</spage><epage>269</epage><pages>257-269</pages><issn>0006-3592</issn><eissn>1097-0290</eissn><coden>BIBIAU</coden><abstract>We describe the design, fabrication, and performance of a bioreactor that enables both morphogenesis of 3D tissue structures under continuous perfusion and repeated in situ observation by light microscopy. Three‐dimensional scaffolds were created by deep reactive ion etching of silicon wafers to create an array of channels (through‐holes) with cell‐adhesive walls. Scaffolds were combined with a cell‐retaining filter and support in a reactor housing designed to deliver a continuous perfusate across the top of the array and through the 3D tissue mass in each channel. Reactor dimensions were constructed so that perfusate flow rates meet estimated values of cellular oxygen demands while providing fluid shear stress at or below a physiological range (<2 dyne cm2), as determined by comparison of numerical models of reactor fluid flow patterns to literature values of physiological shear stresses. We studied the behavior of primary rat hepatocytes seeded into the reactors and cultured for up to 2 weeks, and found that cells seeded into the channels rearranged extensively to form tissue like structures and remained viable throughout the culture period. We further observed that preaggregation of the cells into spheroidal structures prior to seeding improved the morphogenesis of tissue structure and maintenance of viability. We also demonstrate repeated in situ imaging of tissue structure and function using two‐photon microscopy. © 2002 Wiley Periodicals, Inc. Biotechnol Bioeng 78: 257–269, 2002.</abstract><cop>New York</cop><pub>Wiley Subscription Services, Inc., A Wiley Company</pub><pmid>11920442</pmid><doi>10.1002/bit.10143</doi><tpages>13</tpages></addata></record> |
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subjects | Animals Biological and medical sciences bioreactor Bioreactors Biotechnology Cell Culture Techniques Fundamental and applied biological sciences. Psychology gene delivery Green Fluorescent Proteins Hepatocytes - cytology Hepatocytes - physiology Imaging, Three-Dimensional liver Luminescent Proteins - genetics Luminescent Proteins - metabolism Male Methods. Procedures. Technologies Microscopy Morphogenesis - physiology Organ Culture Techniques - methods Organ Culture Techniques - trends Oxygen - physiology Perfusion Rats Space life sciences Stress, Mechanical tissue engineering Tissue Engineering - methods Tissue Engineering - trends Various methods and equipments |
title | A microfabricated array bioreactor for perfused 3D liver culture |
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