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Development and validation of a bioreactor system for dynamic loading and mechanical characterization of whole human intervertebral discs in organ culture
Abstract Intervertebral disc (IVD) degeneration is a common cause of back pain, and attempts to develop therapies are frustrated by lack of model systems that mimic the human condition. Human IVD organ culture models can address this gap, yet current models are limited since vertebral endplates are...
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Published in: | Journal of biomechanics 2014-06, Vol.47 (9), p.2095-2101 |
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creator | Walter, B.A Illien-Jünger, S Nasser, P.R Hecht, A.C Iatridis, J.C |
description | Abstract Intervertebral disc (IVD) degeneration is a common cause of back pain, and attempts to develop therapies are frustrated by lack of model systems that mimic the human condition. Human IVD organ culture models can address this gap, yet current models are limited since vertebral endplates are removed to maintain cell viability, physiological loading is not applied, and mechanical behaviors are not measured. This study aimed to (i) establish a method for isolating human IVDs from autopsy with intact vertebral endplates, and (ii) develop and validate an organ culture loading system for human or bovine IVDs. Human IVDs with intact endplates were isolated from cadavers within 48 h of death and cultured for up to 21 days. IVDs remained viable with ~80% cell viability in nucleus and annulus regions. A dynamic loading system was designed and built with the capacity to culture 9 bovine or 6 human IVDs simultaneously while applying simulated physiologic loads (maximum force: 4 kN) and measuring IVD mechanical behaviors. The loading system accurately applied dynamic loading regimes (RMS error |
doi_str_mv | 10.1016/j.jbiomech.2014.03.015 |
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Human IVD organ culture models can address this gap, yet current models are limited since vertebral endplates are removed to maintain cell viability, physiological loading is not applied, and mechanical behaviors are not measured. This study aimed to (i) establish a method for isolating human IVDs from autopsy with intact vertebral endplates, and (ii) develop and validate an organ culture loading system for human or bovine IVDs. Human IVDs with intact endplates were isolated from cadavers within 48 h of death and cultured for up to 21 days. IVDs remained viable with ~80% cell viability in nucleus and annulus regions. A dynamic loading system was designed and built with the capacity to culture 9 bovine or 6 human IVDs simultaneously while applying simulated physiologic loads (maximum force: 4 kN) and measuring IVD mechanical behaviors. The loading system accurately applied dynamic loading regimes (RMS error <2.5 N and total harmonic distortion <2.45%), and precisely evaluated mechanical behavior of rubber and bovine IVDs. Bovine IVDs maintained their mechanical behavior and retained >85% viable cells throughout the 3 week culture period. This organ culture loading system can closely mimic physiological conditions and be used to investigate response of living human and bovine IVDs to mechanical and chemical challenges and to screen therapeutic repair techniques.</description><identifier>ISSN: 0021-9290</identifier><identifier>EISSN: 1873-2380</identifier><identifier>DOI: 10.1016/j.jbiomech.2014.03.015</identifier><identifier>PMID: 24725441</identifier><language>eng</language><publisher>United States: Elsevier Ltd</publisher><subject>Animals ; Back pain ; Biodegradable materials ; Biomechanical Phenomena ; Bioreactor loading system ; Bioreactors ; Bovine ; Cattle ; Child ; Culture ; Design ; Dynamical systems ; Dynamics ; Female ; Human ; Humans ; Intervertebral disc ; Intervertebral Disc - physiology ; Intervertebral discs ; Loads (forces) ; Male ; Mechanical properties ; Middle Aged ; Muscular system ; Organ culture ; Organ Culture Techniques ; Organs ; Physical Medicine and Rehabilitation ; Reproducibility of Results ; Studies ; Tissue engineering</subject><ispartof>Journal of biomechanics, 2014-06, Vol.47 (9), p.2095-2101</ispartof><rights>Elsevier Ltd</rights><rights>2014 Elsevier Ltd</rights><rights>Copyright © 2014 Elsevier Ltd. All rights reserved.</rights><rights>Copyright Elsevier Limited 2014</rights><rights>2014 Elsevier Ltd. All rights reserved. 2014</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c624t-cd55dc55bee4e92ed3789247b835ab90d8f5504a12bd260737d1e9f93fa6b2113</citedby><cites>FETCH-LOGICAL-c624t-cd55dc55bee4e92ed3789247b835ab90d8f5504a12bd260737d1e9f93fa6b2113</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24725441$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Walter, B.A</creatorcontrib><creatorcontrib>Illien-Jünger, S</creatorcontrib><creatorcontrib>Nasser, P.R</creatorcontrib><creatorcontrib>Hecht, A.C</creatorcontrib><creatorcontrib>Iatridis, J.C</creatorcontrib><title>Development and validation of a bioreactor system for dynamic loading and mechanical characterization of whole human intervertebral discs in organ culture</title><title>Journal of biomechanics</title><addtitle>J Biomech</addtitle><description>Abstract Intervertebral disc (IVD) degeneration is a common cause of back pain, and attempts to develop therapies are frustrated by lack of model systems that mimic the human condition. Human IVD organ culture models can address this gap, yet current models are limited since vertebral endplates are removed to maintain cell viability, physiological loading is not applied, and mechanical behaviors are not measured. This study aimed to (i) establish a method for isolating human IVDs from autopsy with intact vertebral endplates, and (ii) develop and validate an organ culture loading system for human or bovine IVDs. Human IVDs with intact endplates were isolated from cadavers within 48 h of death and cultured for up to 21 days. IVDs remained viable with ~80% cell viability in nucleus and annulus regions. A dynamic loading system was designed and built with the capacity to culture 9 bovine or 6 human IVDs simultaneously while applying simulated physiologic loads (maximum force: 4 kN) and measuring IVD mechanical behaviors. The loading system accurately applied dynamic loading regimes (RMS error <2.5 N and total harmonic distortion <2.45%), and precisely evaluated mechanical behavior of rubber and bovine IVDs. Bovine IVDs maintained their mechanical behavior and retained >85% viable cells throughout the 3 week culture period. This organ culture loading system can closely mimic physiological conditions and be used to investigate response of living human and bovine IVDs to mechanical and chemical challenges and to screen therapeutic repair techniques.</description><subject>Animals</subject><subject>Back pain</subject><subject>Biodegradable materials</subject><subject>Biomechanical Phenomena</subject><subject>Bioreactor loading system</subject><subject>Bioreactors</subject><subject>Bovine</subject><subject>Cattle</subject><subject>Child</subject><subject>Culture</subject><subject>Design</subject><subject>Dynamical systems</subject><subject>Dynamics</subject><subject>Female</subject><subject>Human</subject><subject>Humans</subject><subject>Intervertebral disc</subject><subject>Intervertebral Disc - physiology</subject><subject>Intervertebral discs</subject><subject>Loads (forces)</subject><subject>Male</subject><subject>Mechanical properties</subject><subject>Middle Aged</subject><subject>Muscular system</subject><subject>Organ culture</subject><subject>Organ Culture Techniques</subject><subject>Organs</subject><subject>Physical Medicine and Rehabilitation</subject><subject>Reproducibility of Results</subject><subject>Studies</subject><subject>Tissue engineering</subject><issn>0021-9290</issn><issn>1873-2380</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><recordid>eNqNkstu1DAUhiMEoqXwCpUlNmxmOL4l8aYClatUiQWwthz7ZMZDEg92MtXwKDwtTqcdoBtY2fL5zn8u_ovinMKSAi1fbpabxoce7XrJgIol8CVQ-aA4pXXFF4zX8LA4BWB0oZiCk-JJShsAqESlHhcnTFRMCkFPi59vcIdd2PY4jMQMjuxM550ZfRhIaIkhuUpEY8cQSdqnEXvS5qvbD6b3lnTBOD-sbjLnZszgrelIvsScg9H_OEpdr0OHZD31ZiB-yLEdxhGbmHHnk035kYS4ylE7deMU8WnxqDVdwme351nx9d3bL5cfFlef3n-8fH21sCUT48I6KZ2VskEUqBg6XtUqD9jUXJpGgatbKUEYyhrHSqh45SiqVvHWlA2jlJ8VFwfd7dT06GzeRG5Kb6PvTdzrYLz-OzL4tV6FnRYgKirrLPDiViCG7xOmUfd5IOw6M2CYkqZSUlBcgfwPlDMlFC1ZRp_fQzdhikPexExBnX-yFpkqD5SNIaWI7bFvCnp2it7oO6fo2SkauM5OyYnnf059TLuzRgZeHQDMu995jDpZj4NF5yPaUbvg_13j4p6E7fyNQ77hHtPveXRiGvTn2a-zXakAoDWj_Bccfets</recordid><startdate>20140627</startdate><enddate>20140627</enddate><creator>Walter, B.A</creator><creator>Illien-Jünger, S</creator><creator>Nasser, P.R</creator><creator>Hecht, A.C</creator><creator>Iatridis, J.C</creator><general>Elsevier Ltd</general><general>Elsevier Limited</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>3V.</scope><scope>7QP</scope><scope>7TB</scope><scope>7TS</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>M7P</scope><scope>MBDVC</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>7X8</scope><scope>7U5</scope><scope>L7M</scope><scope>5PM</scope></search><sort><creationdate>20140627</creationdate><title>Development and validation of a bioreactor system for dynamic loading and mechanical characterization of whole human intervertebral discs in organ culture</title><author>Walter, B.A ; Illien-Jünger, S ; Nasser, P.R ; Hecht, A.C ; Iatridis, J.C</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c624t-cd55dc55bee4e92ed3789247b835ab90d8f5504a12bd260737d1e9f93fa6b2113</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Animals</topic><topic>Back pain</topic><topic>Biodegradable materials</topic><topic>Biomechanical Phenomena</topic><topic>Bioreactor loading system</topic><topic>Bioreactors</topic><topic>Bovine</topic><topic>Cattle</topic><topic>Child</topic><topic>Culture</topic><topic>Design</topic><topic>Dynamical systems</topic><topic>Dynamics</topic><topic>Female</topic><topic>Human</topic><topic>Humans</topic><topic>Intervertebral disc</topic><topic>Intervertebral Disc - 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Academic</collection><collection>Solid State and Superconductivity Abstracts</collection><collection>Advanced Technologies Database with Aerospace</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of biomechanics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Walter, B.A</au><au>Illien-Jünger, S</au><au>Nasser, P.R</au><au>Hecht, A.C</au><au>Iatridis, J.C</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Development and validation of a bioreactor system for dynamic loading and mechanical characterization of whole human intervertebral discs in organ culture</atitle><jtitle>Journal of biomechanics</jtitle><addtitle>J Biomech</addtitle><date>2014-06-27</date><risdate>2014</risdate><volume>47</volume><issue>9</issue><spage>2095</spage><epage>2101</epage><pages>2095-2101</pages><issn>0021-9290</issn><eissn>1873-2380</eissn><abstract>Abstract Intervertebral disc (IVD) degeneration is a common cause of back pain, and attempts to develop therapies are frustrated by lack of model systems that mimic the human condition. Human IVD organ culture models can address this gap, yet current models are limited since vertebral endplates are removed to maintain cell viability, physiological loading is not applied, and mechanical behaviors are not measured. This study aimed to (i) establish a method for isolating human IVDs from autopsy with intact vertebral endplates, and (ii) develop and validate an organ culture loading system for human or bovine IVDs. Human IVDs with intact endplates were isolated from cadavers within 48 h of death and cultured for up to 21 days. IVDs remained viable with ~80% cell viability in nucleus and annulus regions. A dynamic loading system was designed and built with the capacity to culture 9 bovine or 6 human IVDs simultaneously while applying simulated physiologic loads (maximum force: 4 kN) and measuring IVD mechanical behaviors. The loading system accurately applied dynamic loading regimes (RMS error <2.5 N and total harmonic distortion <2.45%), and precisely evaluated mechanical behavior of rubber and bovine IVDs. Bovine IVDs maintained their mechanical behavior and retained >85% viable cells throughout the 3 week culture period. This organ culture loading system can closely mimic physiological conditions and be used to investigate response of living human and bovine IVDs to mechanical and chemical challenges and to screen therapeutic repair techniques.</abstract><cop>United States</cop><pub>Elsevier Ltd</pub><pmid>24725441</pmid><doi>10.1016/j.jbiomech.2014.03.015</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Animals Back pain Biodegradable materials Biomechanical Phenomena Bioreactor loading system Bioreactors Bovine Cattle Child Culture Design Dynamical systems Dynamics Female Human Humans Intervertebral disc Intervertebral Disc - physiology Intervertebral discs Loads (forces) Male Mechanical properties Middle Aged Muscular system Organ culture Organ Culture Techniques Organs Physical Medicine and Rehabilitation Reproducibility of Results Studies Tissue engineering |
title | Development and validation of a bioreactor system for dynamic loading and mechanical characterization of whole human intervertebral discs in organ culture |
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