Characterizing accelerated capture of deoligomerized TNF within hemoadsorption beads used to treat sepsis
Identifieur interne : 001A13 ( Istex/Corpus ); précédent : 001A12; suivant : 001A14Characterizing accelerated capture of deoligomerized TNF within hemoadsorption beads used to treat sepsis
Auteurs : Jeremy D. Kimmel ; Christopher S. Lacko ; Russell L. Delude ; William J. FederspielSource :
- Journal of Biomedical Materials Research Part B: Applied Biomaterials [ 1552-4973 ] ; 2011-07.
English descriptors
- KwdEn :
- Adsorption, Appl biomater, Biol chem, Biomed mater, Biomedical materials research, Crit care, Crosslinked, Cytokine, Cytokine concentrations, Dmso, Dmso incubation, Elisa, Hemoadsorption, Hemoadsorption beads, Hemoadsorption device, Horse serum, Human serum, Ltration, Ltration chromatography, Molecular size, Monomeric, Necrosis, Oligomeric, Pore, Receptor, Same manner, Sepsis, Slower rate, Solid lines, Sorbent, Sorbent device, Sorbent pores, Sorbent surface, Spiked, Trimeric, Tumor necrosis, Tumor necrosis factor.
- Teeft :
- Adsorption, Appl biomater, Biol chem, Biomed mater, Biomedical materials research, Crit care, Crosslinked, Cytokine, Cytokine concentrations, Dmso, Dmso incubation, Elisa, Hemoadsorption, Hemoadsorption beads, Hemoadsorption device, Horse serum, Human serum, Ltration, Ltration chromatography, Molecular size, Monomeric, Necrosis, Oligomeric, Pore, Receptor, Same manner, Sepsis, Slower rate, Solid lines, Sorbent, Sorbent device, Sorbent pores, Sorbent surface, Spiked, Trimeric, Tumor necrosis, Tumor necrosis factor.
Abstract
Sepsis is a systemic inflammatory response to infection, characterized by overexpression of cytokines in the circulating blood. Removal of cytokines and other inflammatory mediators from the blood may help attenuate systemic inflammation during sepsis and improve patient outcomes. In this work, we examined the dynamics of TNF capture within porous, polymeric sorbent beads used in a cytokine adsorption device. We sought to quantify how perturbation of TNF oligomeric structure accelerates TNF removal within the device. TNF was incubated with 10% DMSO for 24 h, which promoted complete monomerization of trimeric TNF, and accelerated TNF capture within the sorbent device compared with native TNF; removal halftime = 13.3 ± 1.5 min versus 112.8 ± 13.3 min, respectively. Intramolecular crosslinking stabilized the trimeric TNF structure and prevented DMSO monomerization. Results demonstrate that TNF is an unstable oligomeric molecule that can be dissociated into its smaller monomeric constituents to facilitate faster capture by hemoadsorption beads. Strategies to promote localized TNF deoligomerization at the sorbent surface may significantly accelerate TNF capture rates from the circulating blood using hemoadsorption as a treatment for sepsis. This concept could be extended to improve removal of other oligomeric molecules using size exclusion filtration materials for a variety of disease states. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2011.
Url:
DOI: 10.1002/jbm.b.31830
Links to Exploration step
ISTEX:71803EC3E1820EC4EFB9074939B3C92442AC0F23Le document en format XML
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Removal of cytokines and other inflammatory mediators from the blood may help attenuate systemic inflammation during sepsis and improve patient outcomes. In this work, we examined the dynamics of TNF capture within porous, polymeric sorbent beads used in a cytokine adsorption device. We sought to quantify how perturbation of TNF oligomeric structure accelerates TNF removal within the device. TNF was incubated with 10% DMSO for 24 h, which promoted complete monomerization of trimeric TNF, and accelerated TNF capture within the sorbent device compared with native TNF; removal halftime = 13.3 ± 1.5 min versus 112.8 ± 13.3 min, respectively. Intramolecular crosslinking stabilized the trimeric TNF structure and prevented DMSO monomerization. Results demonstrate that TNF is an unstable oligomeric molecule that can be dissociated into its smaller monomeric constituents to facilitate faster capture by hemoadsorption beads. Strategies to promote localized TNF deoligomerization at the sorbent surface may significantly accelerate TNF capture rates from the circulating blood using hemoadsorption as a treatment for sepsis. This concept could be extended to improve removal of other oligomeric molecules using size exclusion filtration materials for a variety of disease states. © 2011 Wiley Periodicals, Inc. 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Kimmel</name><affiliations><json:string>Department of Bioengineering, University of Pittsburgh, Pittsburgh, Pennsylvania</json:string><json:string>McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania</json:string></affiliations></json:item><json:item><name>Christopher S. Lacko</name><affiliations><json:string>Departments of Materials Science Engineering and Biomedical Engineering, Carnegie Mellon University, Pittsburgh, Pennsylvania</json:string></affiliations></json:item><json:item><name>Russell L. Delude</name><affiliations><json:string>Department of Critical Care Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania</json:string></affiliations></json:item><json:item><name>William J. Federspiel</name><affiliations><json:string>Department of Bioengineering, University of Pittsburgh, Pittsburgh, Pennsylvania</json:string><json:string>McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania</json:string><json:string>Department of Critical Care Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania</json:string><json:string>Department of Chemical and Petroleum Engineering, University of Pittsburgh, Pittsburgh, Pennsylvania</json:string><json:string>E-mail: federspielwj@upmc.edu</json:string><json:string>Correspondence address: Department of Bioengineering, University of Pittsburgh, Pittsburgh, Pennsylvania</json:string></affiliations></json:item></author><subject><json:item><lang><json:string>eng</json:string></lang><value>TNF</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>sepsis</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>blood purification</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>hemoadsorption</value></json:item></subject><articleId><json:string>JBM31830</json:string></articleId><arkIstex>ark:/67375/WNG-HJ16V2NJ-V</arkIstex><language><json:string>eng</json:string></language><originalGenre><json:string>article</json:string></originalGenre><abstract>Sepsis is a systemic inflammatory response to infection, characterized by overexpression of cytokines in the circulating blood. Removal of cytokines and other inflammatory mediators from the blood may help attenuate systemic inflammation during sepsis and improve patient outcomes. In this work, we examined the dynamics of TNF capture within porous, polymeric sorbent beads used in a cytokine adsorption device. We sought to quantify how perturbation of TNF oligomeric structure accelerates TNF removal within the device. TNF was incubated with 10% DMSO for 24 h, which promoted complete monomerization of trimeric TNF, and accelerated TNF capture within the sorbent device compared with native TNF; removal halftime = 13.3 ± 1.5 min versus 112.8 ± 13.3 min, respectively. Intramolecular crosslinking stabilized the trimeric TNF structure and prevented DMSO monomerization. Results demonstrate that TNF is an unstable oligomeric molecule that can be dissociated into its smaller monomeric constituents to facilitate faster capture by hemoadsorption beads. Strategies to promote localized TNF deoligomerization at the sorbent surface may significantly accelerate TNF capture rates from the circulating blood using hemoadsorption as a treatment for sepsis. This concept could be extended to improve removal of other oligomeric molecules using size exclusion filtration materials for a variety of disease states. © 2011 Wiley Periodicals, Inc. 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Lacko</json:string><json:string>William J. Federspiel</json:string><json:string>Russell L. Delude</json:string><json:string>Franklin Lakes</json:string><json:string>W. J. Federspiel</json:string><json:string>Fisher Scienti</json:string></persName><placeName></placeName><ref_url></ref_url><ref_bibl></ref_bibl><bibl></bibl></unitex></namedEntities><ark><json:string>ark:/67375/WNG-HJ16V2NJ-V</json:string></ark><categories><inist><json:string>1 - sciences appliquees, technologies et medecines</json:string><json:string>2 - sciences biologiques et medicales</json:string><json:string>3 - sciences medicales</json:string><json:string>4 - nephrologie. maladies des voies urinaires</json:string></inist></categories><publicationDate>2011</publicationDate><copyrightDate>2011</copyrightDate><doi><json:string>10.1002/jbm.b.31830</json:string></doi><id>71803EC3E1820EC4EFB9074939B3C92442AC0F23</id><score>1</score><fulltext><json:item><extension>pdf</extension><original>true</original><mimetype>application/pdf</mimetype><uri>https://api.istex.fr/document/71803EC3E1820EC4EFB9074939B3C92442AC0F23/fulltext/pdf</uri></json:item><json:item><extension>zip</extension><original>false</original><mimetype>application/zip</mimetype><uri>https://api.istex.fr/document/71803EC3E1820EC4EFB9074939B3C92442AC0F23/fulltext/zip</uri></json:item><istex:fulltextTEI uri="https://api.istex.fr/document/71803EC3E1820EC4EFB9074939B3C92442AC0F23/fulltext/tei"><teiHeader><fileDesc><titleStmt><title level="a" type="main" xml:lang="en">Characterizing accelerated capture of deoligomerized TNF within hemoadsorption beads used to treat 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type="first">Jeremy D.</forename><surname>Kimmel</surname></persName><affiliation>Department of Bioengineering, University of Pittsburgh, Pittsburgh, Pennsylvania<address><country key="US"></country></address></affiliation><affiliation>McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania<address><country key="US"></country></address></affiliation></author><author xml:id="author-0001"><persName><forename type="first">Christopher S.</forename><surname>Lacko</surname></persName><affiliation>Departments of Materials Science Engineering and Biomedical Engineering, Carnegie Mellon University, Pittsburgh, Pennsylvania<address><country key="US"></country></address></affiliation></author><author xml:id="author-0002"><persName><forename type="first">Russell L.</forename><surname>Delude</surname></persName><affiliation>Department of Critical Care Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania<address><country key="US"></country></address></affiliation></author><author xml:id="author-0003" role="corresp"><persName><forename type="first">William J.</forename><surname>Federspiel</surname></persName><email>federspielwj@upmc.edu</email><affiliation>Department of Bioengineering, University of Pittsburgh, Pittsburgh, Pennsylvania<address><country key="US"></country></address></affiliation><affiliation>McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania<address><country key="US"></country></address></affiliation><affiliation>Department of Critical Care Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania<address><country key="US"></country></address></affiliation><affiliation>Department of Chemical and Petroleum Engineering, University of Pittsburgh, Pittsburgh, Pennsylvania<address><country key="US"></country></address></affiliation><affiliation>Department of Bioengineering, University of Pittsburgh, Pittsburgh, Pennsylvania</affiliation></author><idno type="istex">71803EC3E1820EC4EFB9074939B3C92442AC0F23</idno><idno type="ark">ark:/67375/WNG-HJ16V2NJ-V</idno><idno type="DOI">10.1002/jbm.b.31830</idno><idno type="unit">JBM31830</idno><idno type="toTypesetVersion">file:JBM.JBM31830.pdf</idno></analytic><monogr><title level="j" type="main">Journal of Biomedical Materials Research Part B: Applied Biomaterials</title><title level="j" type="alt">JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART B: APPLIED BIOMATERIALS</title><idno type="pISSN">1552-4973</idno><idno type="eISSN">1552-4981</idno><idno type="book-DOI">10.1002/(ISSN)1552-4981</idno><idno type="book-part-DOI">10.1002/jbm.b.v98b.1</idno><idno type="product">JBM</idno><imprint><biblScope unit="vol">98B</biblScope><biblScope unit="issue">1</biblScope><biblScope unit="page" from="47">47</biblScope><biblScope unit="page" to="53">53</biblScope><biblScope unit="page-count">7</biblScope><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><date type="published" when="2011-07"></date></imprint></monogr></biblStruct></sourceDesc></fileDesc><profileDesc><abstract xml:lang="en" style="main"><head>Abstract</head><p>Sepsis is a systemic inflammatory response to infection, characterized by overexpression of cytokines in the circulating blood. Removal of cytokines and other inflammatory mediators from the blood may help attenuate systemic inflammation during sepsis and improve patient outcomes. In this work, we examined the dynamics of TNF capture within porous, polymeric sorbent beads used in a cytokine adsorption device. We sought to quantify how perturbation of TNF oligomeric structure accelerates TNF removal within the device. TNF was incubated with 10% DMSO for 24 h, which promoted complete monomerization of trimeric TNF, and accelerated TNF capture within the sorbent device compared with native TNF; removal halftime = 13.3 ± 1.5 min <hi rend="italic">versus</hi> 112.8 ± 13.3 min, respectively. Intramolecular crosslinking stabilized the trimeric TNF structure and prevented DMSO monomerization. Results demonstrate that TNF is an unstable oligomeric molecule that can be dissociated into its smaller monomeric constituents to facilitate faster capture by hemoadsorption beads. Strategies to promote localized TNF deoligomerization at the sorbent surface may significantly accelerate TNF capture rates from the circulating blood using hemoadsorption as a treatment for sepsis. This concept could be extended to improve removal of other oligomeric molecules using size exclusion filtration materials for a variety of disease states. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2011.</p></abstract><textClass><keywords xml:lang="en"><term xml:id="kwd1">TNF</term><term xml:id="kwd2">sepsis</term><term xml:id="kwd3">blood purification</term><term xml:id="kwd4">hemoadsorption</term></keywords></textClass><langUsage><language ident="en"></language></langUsage></profileDesc></teiHeader></istex:fulltextTEI><json:item><extension>txt</extension><original>false</original><mimetype>text/plain</mimetype><uri>https://api.istex.fr/document/71803EC3E1820EC4EFB9074939B3C92442AC0F23/fulltext/txt</uri></json:item></fulltext><metadata><istex:metadataXml wicri:clean="Wiley, elements deleted: body"><istex:xmlDeclaration>version="1.0" encoding="UTF-8" standalone="yes"</istex:xmlDeclaration><istex:document><component version="2.0" type="serialArticle" xml:lang="en"><header><publicationMeta level="product"><publisherInfo><publisherName>Wiley Subscription Services, Inc., A Wiley Company</publisherName><publisherLoc>Hoboken</publisherLoc></publisherInfo><doi registered="yes">10.1002/(ISSN)1552-4981</doi><issn type="print">1552-4973</issn><issn type="electronic">1552-4981</issn><idGroup><id type="product" value="JBM"></id></idGroup><titleGroup><title type="main" xml:lang="en" sort="JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART B: APPLIED BIOMATERIALS">Journal of Biomedical Materials Research Part B: Applied Biomaterials</title><title type="short">J. Biomed. Mater. Res.</title></titleGroup><selfCitationGroup><citation type="ancestor" xml:id="cit1"><journalTitle>Journal of Biomedical Materials Research</journalTitle><accessionId ref="info:x-wiley/issn/00219304">0021-9304</accessionId><accessionId ref="info:x-wiley/issn/10974636">1097-4636</accessionId><pubYear year="2004">2004</pubYear></citation></selfCitationGroup></publicationMeta><publicationMeta level="part" position="10"><doi origin="wiley" registered="yes">10.1002/jbm.b.v98b.1</doi><numberingGroup><numbering type="journalVolume" number="98">98B</numbering><numbering type="journalIssue">1</numbering></numberingGroup><coverDate startDate="2011-07">July 2011</coverDate></publicationMeta><publicationMeta level="unit" type="article" position="60" status="forIssue"><doi origin="wiley" registered="yes">10.1002/jbm.b.31830</doi><idGroup><id type="unit" value="JBM31830"></id></idGroup><countGroup><count type="pageTotal" number="7"></count></countGroup><copyright ownership="publisher">Copyright © 2011 Wiley Periodicals, Inc.</copyright><eventGroup><event type="manuscriptReceived" date="2010-11-02"></event><event type="manuscriptRevised" date="2011-01-17"></event><event type="manuscriptAccepted" date="2011-02-03"></event><event type="xmlConverted" agent="Converter:JWSART34_TO_WML3G version:2.5 mode:FullText" date="2011-06-01"></event><event type="publishedOnlineEarlyUnpaginated" date="2011-04-18"></event><event type="firstOnline" date="2011-04-18"></event><event type="publishedOnlineFinalForm" date="2011-06-01"></event><event type="xmlConverted" agent="Converter:WILEY_ML3G_TO_WILEY_ML3GV2 version:3.8.8" date="2014-01-29"></event><event type="xmlConverted" agent="Converter:WML3G_To_WML3G version:4.1.7 mode:FullText,remove_FC" date="2014-10-24"></event></eventGroup><numberingGroup><numbering type="pageFirst">47</numbering><numbering type="pageLast">53</numbering></numberingGroup><correspondenceTo>Department of Bioengineering, University of Pittsburgh, Pittsburgh, Pennsylvania</correspondenceTo><linkGroup><link type="toTypesetVersion" href="file:JBM.JBM31830.pdf"></link></linkGroup></publicationMeta><contentMeta><countGroup><count type="figureTotal" number="6"></count><count type="tableTotal" number="0"></count><count type="referenceTotal" number="36"></count><count type="wordTotal" number="5801"></count></countGroup><titleGroup><title type="main" xml:lang="en">Characterizing accelerated capture of deoligomerized TNF within hemoadsorption beads used to treat sepsis</title><title type="short" xml:lang="en">Capture of Deoligomerized TNF within Hemoadsorption Beads</title></titleGroup><creators><creator xml:id="au1" creatorRole="author" affiliationRef="#af1 #af2"><personName><givenNames>Jeremy D.</givenNames><familyName>Kimmel</familyName></personName></creator><creator xml:id="au2" creatorRole="author" affiliationRef="#af3"><personName><givenNames>Christopher S.</givenNames><familyName>Lacko</familyName></personName></creator><creator xml:id="au3" creatorRole="author" affiliationRef="#af4"><personName><givenNames>Russell L.</givenNames><familyName>Delude</familyName></personName></creator><creator xml:id="au4" creatorRole="author" affiliationRef="#af1 #af2 #af4 #af5" corresponding="yes"><personName><givenNames>William J.</givenNames><familyName>Federspiel</familyName></personName><contactDetails><email>federspielwj@upmc.edu</email></contactDetails></creator></creators><affiliationGroup><affiliation xml:id="af1" countryCode="US" type="organization"><unparsedAffiliation>Department of Bioengineering, University of Pittsburgh, Pittsburgh, Pennsylvania</unparsedAffiliation></affiliation><affiliation xml:id="af2" countryCode="US" type="organization"><unparsedAffiliation>McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania</unparsedAffiliation></affiliation><affiliation xml:id="af3" countryCode="US" type="organization"><unparsedAffiliation>Departments of Materials Science Engineering and Biomedical Engineering, Carnegie Mellon University, Pittsburgh, Pennsylvania</unparsedAffiliation></affiliation><affiliation xml:id="af4" countryCode="US" type="organization"><unparsedAffiliation>Department of Critical Care Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania</unparsedAffiliation></affiliation><affiliation xml:id="af5" countryCode="US" type="organization"><unparsedAffiliation>Department of Chemical and Petroleum Engineering, University of Pittsburgh, Pittsburgh, Pennsylvania</unparsedAffiliation></affiliation></affiliationGroup><keywordGroup xml:lang="en" type="author"><keyword xml:id="kwd1">TNF</keyword><keyword xml:id="kwd2">sepsis</keyword><keyword xml:id="kwd3">blood purification</keyword><keyword xml:id="kwd4">hemoadsorption</keyword></keywordGroup><fundingInfo><fundingAgency>National Institutes of Health (NIH): National Heart, Lung, and Blood Institute</fundingAgency><fundingNumber>HL080926‐02</fundingNumber></fundingInfo><fundingInfo><fundingAgency>Public Health Services (PHS)</fundingAgency><fundingNumber>1‐T32‐HL07612403</fundingNumber></fundingInfo><abstractGroup><abstract type="main" xml:lang="en"><title type="main">Abstract</title><p>Sepsis is a systemic inflammatory response to infection, characterized by overexpression of cytokines in the circulating blood. Removal of cytokines and other inflammatory mediators from the blood may help attenuate systemic inflammation during sepsis and improve patient outcomes. In this work, we examined the dynamics of TNF capture within porous, polymeric sorbent beads used in a cytokine adsorption device. We sought to quantify how perturbation of TNF oligomeric structure accelerates TNF removal within the device. TNF was incubated with 10% DMSO for 24 h, which promoted complete monomerization of trimeric TNF, and accelerated TNF capture within the sorbent device compared with native TNF; removal halftime = 13.3 ± 1.5 min <i>versus</i> 112.8 ± 13.3 min, respectively. Intramolecular crosslinking stabilized the trimeric TNF structure and prevented DMSO monomerization. Results demonstrate that TNF is an unstable oligomeric molecule that can be dissociated into its smaller monomeric constituents to facilitate faster capture by hemoadsorption beads. Strategies to promote localized TNF deoligomerization at the sorbent surface may significantly accelerate TNF capture rates from the circulating blood using hemoadsorption as a treatment for sepsis. This concept could be extended to improve removal of other oligomeric molecules using size exclusion filtration materials for a variety of disease states. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2011.</p></abstract></abstractGroup></contentMeta></header></component></istex:document></istex:metadataXml><mods version="3.6"><titleInfo lang="en"><title>Characterizing accelerated capture of deoligomerized TNF within hemoadsorption beads used to treat sepsis</title></titleInfo><titleInfo type="abbreviated" lang="en"><title>Capture of Deoligomerized TNF within Hemoadsorption Beads</title></titleInfo><titleInfo type="alternative" contentType="CDATA" lang="en"><title>Characterizing accelerated capture of deoligomerized TNF within hemoadsorption beads used to treat sepsis</title></titleInfo><name type="personal"><namePart type="given">Jeremy D.</namePart><namePart type="family">Kimmel</namePart><affiliation>Department of Bioengineering, University of Pittsburgh, Pittsburgh, Pennsylvania</affiliation><affiliation>McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Christopher S.</namePart><namePart type="family">Lacko</namePart><affiliation>Departments of Materials Science Engineering and Biomedical Engineering, Carnegie Mellon University, Pittsburgh, Pennsylvania</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Russell L.</namePart><namePart type="family">Delude</namePart><affiliation>Department of Critical Care Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">William J.</namePart><namePart type="family">Federspiel</namePart><affiliation>Department of Bioengineering, University of Pittsburgh, Pittsburgh, Pennsylvania</affiliation><affiliation>McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania</affiliation><affiliation>Department of Critical Care Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania</affiliation><affiliation>Department of Chemical and Petroleum Engineering, University of Pittsburgh, Pittsburgh, Pennsylvania</affiliation><affiliation>E-mail: federspielwj@upmc.edu</affiliation><affiliation>Correspondence address: Department of Bioengineering, University of Pittsburgh, Pittsburgh, Pennsylvania</affiliation><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="article" displayLabel="article" authority="ISTEX" authorityURI="https://content-type.data.istex.fr" valueURI="https://content-type.data.istex.fr/ark:/67375/XTP-6N5SZHKN-D">article</genre><originInfo><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><place><placeTerm type="text">Hoboken</placeTerm></place><dateIssued encoding="w3cdtf">2011-07</dateIssued><dateCaptured encoding="w3cdtf">2010-11-02</dateCaptured><dateValid encoding="w3cdtf">2011-02-03</dateValid><copyrightDate encoding="w3cdtf">2011</copyrightDate></originInfo><language><languageTerm type="code" authority="rfc3066">en</languageTerm><languageTerm type="code" authority="iso639-2b">eng</languageTerm></language><physicalDescription><extent unit="figures">6</extent><extent unit="tables">0</extent><extent unit="references">36</extent><extent unit="words">5801</extent></physicalDescription><abstract lang="en">Sepsis is a systemic inflammatory response to infection, characterized by overexpression of cytokines in the circulating blood. Removal of cytokines and other inflammatory mediators from the blood may help attenuate systemic inflammation during sepsis and improve patient outcomes. In this work, we examined the dynamics of TNF capture within porous, polymeric sorbent beads used in a cytokine adsorption device. We sought to quantify how perturbation of TNF oligomeric structure accelerates TNF removal within the device. TNF was incubated with 10% DMSO for 24 h, which promoted complete monomerization of trimeric TNF, and accelerated TNF capture within the sorbent device compared with native TNF; removal halftime = 13.3 ± 1.5 min versus 112.8 ± 13.3 min, respectively. Intramolecular crosslinking stabilized the trimeric TNF structure and prevented DMSO monomerization. Results demonstrate that TNF is an unstable oligomeric molecule that can be dissociated into its smaller monomeric constituents to facilitate faster capture by hemoadsorption beads. Strategies to promote localized TNF deoligomerization at the sorbent surface may significantly accelerate TNF capture rates from the circulating blood using hemoadsorption as a treatment for sepsis. This concept could be extended to improve removal of other oligomeric molecules using size exclusion filtration materials for a variety of disease states. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2011.</abstract><note type="funding">National Institutes of Health (NIH): National Heart, Lung, and Blood Institute - No. HL080926‐02; </note><note type="funding">Public Health Services (PHS) - No. 1‐T32‐HL07612403; </note><subject lang="en"><genre>keywords</genre><topic>TNF</topic><topic>sepsis</topic><topic>blood purification</topic><topic>hemoadsorption</topic></subject><relatedItem type="host"><titleInfo><title>Journal of Biomedical Materials Research Part B: Applied Biomaterials</title></titleInfo><titleInfo type="abbreviated"><title>J. Biomed. Mater. 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