{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T22:36:04Z","timestamp":1791326164113,"version":"4.3.1"},"reference-count":82,"publisher":"Wiley","issue":"21","license":[{"start":{"date-parts":[[2022,4,18]],"date-time":"2022-04-18T00:00:00Z","timestamp":1650240000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["UG3\/UH3TR002136"],"award-info":[{"award-number":["UG3\/UH3TR002136"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["UG3\/UH3TR003090"],"award-info":[{"award-number":["UG3\/UH3TR003090"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P41EB023833"],"award-info":[{"award-number":["P41EB023833"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P30CA047904"],"award-info":[{"award-number":["P30CA047904"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"published-print":{"date-parts":[[2022,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Diseases of the knee joint such as osteoarthritis (OA) affect all joint elements. An in vitro human cell\u2010derived microphysiological system capable of simulating intraarticular tissue crosstalk is desirable for studying etiologies\/pathogenesis of joint diseases and testing potential therapeutics. Herein, a human mesenchymal stem cell\u2010derived miniature joint system (miniJoint) is generated, in which engineered osteochondral complex, synovial\u2010like fibrous tissue, and adipose tissue are integrated into a microfluidics\u2010enabled bioreactor. This novel design facilitates different tissues communicating while still maintaining their respective phenotypes. The miniJoint exhibits physiologically relevant changes when exposed to interleukin\u20101\n                    <jats:italic>\u03b2<\/jats:italic>\n                    mediated inflammation, which are similar to observations in joint diseases in humans. The potential of the miniJoint in predicting in vivo efficacy of drug treatment is confirmed by testing the \u201ctherapeutic effect\u201d of the nonsteroidal anti\u2010inflammatory drug, naproxen, as well as four other potential disease\u2010modifying OA drugs. The data demonstrate that the miniJoint recapitulates complex tissue interactions, thus providing a robust organ chip model for the study of joint pathology and the development of novel therapeutic interventions.\n                  <\/jats:p>","DOI":"10.1002\/advs.202105909","type":"journal-article","created":{"date-parts":[[2022,4,18]],"date-time":"2022-04-18T08:46:19Z","timestamp":1650271579000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":57,"title":["Human Mesenchymal Stem Cell\u2010Derived Miniature Joint System for Disease Modeling and Drug Testing"],"prefix":"10.1002","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6009-629X","authenticated-orcid":false,"given":"Zhong","family":"Li","sequence":"first","affiliation":[{"name":"Center for Cellular and Molecular Engineering Department of Orthopaedic Surgery University of Pittsburgh School of Medicine  Pittsburgh PA 15219 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zixuan","family":"Lin","sequence":"additional","affiliation":[{"name":"Center for Cellular and Molecular Engineering Department of Orthopaedic Surgery University of Pittsburgh School of Medicine  Pittsburgh PA 15219 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Pittsburgh School of Medicine  Pittsburgh PA 15261 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haruyo","family":"Yagi","sequence":"additional","affiliation":[{"name":"Center for Cellular and Molecular Engineering Department of Orthopaedic Surgery University of Pittsburgh School of Medicine  Pittsburgh PA 15219 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiurui","family":"Zhang","sequence":"additional","affiliation":[{"name":"Center for Cellular and Molecular Engineering Department of Orthopaedic Surgery University of Pittsburgh School of Medicine  Pittsburgh PA 15219 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren","family":"Yocum","sequence":"additional","affiliation":[{"name":"Center for Cellular and Molecular Engineering Department of Orthopaedic Surgery University of Pittsburgh School of Medicine  Pittsburgh PA 15219 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Romero\u2010Lopez","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery Stanford University  Stanford CA 94305 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire","family":"Rhee","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery Stanford University  Stanford CA 94305 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meagan J.","family":"Makarcyzk","sequence":"additional","affiliation":[{"name":"Center for Cellular and Molecular Engineering Department of Orthopaedic Surgery University of Pittsburgh School of Medicine  Pittsburgh PA 15219 USA"},{"name":"Department of Bioengineering University of Pittsburgh Swanson School of Engineering  Pittsburgh PA 15260 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilhan","family":"Yu","sequence":"additional","affiliation":[{"name":"Center for Cellular and Molecular Engineering Department of Orthopaedic Surgery University of Pittsburgh School of Medicine  Pittsburgh PA 15219 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eileen N.","family":"Li","sequence":"additional","affiliation":[{"name":"Center for Cellular and Molecular Engineering Department of Orthopaedic Surgery University of Pittsburgh School of Medicine  Pittsburgh PA 15219 USA"},{"name":"Department of Bioengineering University of Pittsburgh Swanson School of Engineering  Pittsburgh PA 15260 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madalyn R.","family":"Fritch","sequence":"additional","affiliation":[{"name":"Center for Cellular and Molecular Engineering Department of Orthopaedic Surgery University of Pittsburgh School of Medicine  Pittsburgh PA 15219 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery Stanford University  Stanford CA 94305 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kek Boon","family":"Goh","sequence":"additional","affiliation":[{"name":"Institute of Physics University of Freiburg  Freiburg 79104 Germany"},{"name":"School of Engineering Monash University Malaysia  Selangor 47500 Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamen","family":"O'Donnell","sequence":"additional","affiliation":[{"name":"Center for Stem Cell Research and Regenerative Medicine Tulane University School of Medicine  Orleans LA 70112 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingjun","family":"Hao","sequence":"additional","affiliation":[{"name":"Center for Cellular and Molecular Engineering Department of Orthopaedic Surgery University of Pittsburgh School of Medicine  Pittsburgh PA 15219 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter G.","family":"Alexander","sequence":"additional","affiliation":[{"name":"Center for Cellular and Molecular Engineering Department of Orthopaedic Surgery University of Pittsburgh School of Medicine  Pittsburgh PA 15219 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bhushan","family":"Mahadik","sequence":"additional","affiliation":[{"name":"Fischell Department of Bioengineering University of Maryland  College Park MD 20742 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John P.","family":"Fisher","sequence":"additional","affiliation":[{"name":"Fischell Department of Bioengineering University of Maryland  College Park MD 20742 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1919-3717","authenticated-orcid":false,"given":"Stuart B.","family":"Goodman","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery Stanford University  Stanford CA 94305 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6196-3722","authenticated-orcid":false,"given":"Bruce A.","family":"Bunnell","sequence":"additional","affiliation":[{"name":"Center for Stem Cell Research and Regenerative Medicine Tulane University School of Medicine  Orleans LA 70112 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6067-6705","authenticated-orcid":false,"given":"Rocky S.","family":"Tuan","sequence":"additional","affiliation":[{"name":"Center for Cellular and Molecular Engineering Department of Orthopaedic Surgery University of Pittsburgh School of Medicine  Pittsburgh PA 15219 USA"},{"name":"Department of Bioengineering University of Pittsburgh Swanson School of Engineering  Pittsburgh PA 15260 USA"},{"name":"McGowan Institute for Regenerative Medicine University of Pittsburgh School of Medicine  Pittsburgh PA 15219 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0781-6630","authenticated-orcid":false,"given":"Hang","family":"Lin","sequence":"additional","affiliation":[{"name":"Center for Cellular and Molecular Engineering Department of Orthopaedic Surgery University of Pittsburgh School of Medicine  Pittsburgh PA 15219 USA"},{"name":"Department of Bioengineering University of Pittsburgh Swanson School of Engineering  Pittsburgh PA 15260 USA"},{"name":"McGowan Institute for Regenerative Medicine University of Pittsburgh School of Medicine  Pittsburgh PA 15219 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,4,18]]},"reference":[{"key":"e_1_2_10_1_1","doi-asserted-by":"publisher","DOI":"10.1089\/ten.tec.2020.0309"},{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.34453"},{"key":"e_1_2_10_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41413-018-0016-9"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/boneres.2016.28"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1177\/1759720X12467868"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/biology9080194"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.2989"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibtech.2019.03.003"},{"key":"e_1_2_10_7_2","doi-asserted-by":"publisher","DOI":"10.1177\/1535370214539232"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1021\/mp500136b"},{"key":"e_1_2_10_8_2","doi-asserted-by":"publisher","DOI":"10.3389\/fbioe.2019.00411"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41551-019-0406-3"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2013.12.003"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2018.06.026"},{"key":"e_1_2_10_11_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aaz5913"},{"key":"e_1_2_10_11_3","doi-asserted-by":"publisher","DOI":"10.1089\/ten.tea.2008.0393"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13075-017-1229-9"},{"key":"e_1_2_10_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2016.136"},{"key":"e_1_2_10_12_3","doi-asserted-by":"publisher","DOI":"10.1038\/nature01661"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2021.155546"},{"key":"e_1_2_10_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2012.130"},{"key":"e_1_2_10_13_3","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2017.50"},{"key":"e_1_2_10_13_4","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.2828"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2013.06.004"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2018.07.012"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2018.19319"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13075-015-0747-6"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41551-019-0495-z"},{"key":"e_1_2_10_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2018.02.011"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2018.11.036"},{"key":"e_1_2_10_19_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1720658115"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aaz7492"},{"key":"e_1_2_10_20_2","doi-asserted-by":"publisher","DOI":"10.1242\/dmm.034827"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar3022"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2012.05.002"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.40056"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/764621"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1089\/ten.tea.2008.0205"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.0105-2896.2009.00859.x"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-019-1359-x"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1088\/1758-5090\/ac0c5e"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1039\/D0LC00417K"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1089\/ten.tea.2020.0041"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2014.10.017"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2014-205894"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2017.511"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0103056"},{"key":"e_1_2_10_34_2","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2014-205980"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aax2332"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2009.07.009"},{"key":"e_1_2_10_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbspin.2015.01.023"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2015.10.014"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1209294110"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.18632\/aging.102784"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.37823"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.38933"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2013.04.003"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.22203\/eCM.v029a10"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar1846"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1007\/s003930050161"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1002\/jor.24937"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2019.14735"},{"key":"e_1_2_10_47_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2017.07.006"},{"key":"e_1_2_10_47_3","doi-asserted-by":"publisher","DOI":"10.1002\/art.24096"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1053\/joca.2002.0514"},{"key":"e_1_2_10_48_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2005.03.003"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.96308"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13075-019-2003-y"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1319569111"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.1089\/ten.tea.2013.0642"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2005.09.002"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.1089\/ten.tea.2018.0142"},{"key":"e_1_2_10_55_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10439-018-2010-1"},{"key":"e_1_2_10_56_1","doi-asserted-by":"publisher","DOI":"10.22203\/eCM.v038a17"},{"key":"e_1_2_10_57_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13075-014-0441-0"},{"key":"e_1_2_10_58_1","unstructured":"S.Andrews FastQC \u2010 A quality control tool for high throughput sequence data http:\/\/bioinformatics.babraham.ac.uk\/projects\/fastqc\/ Babraham Bioinforma http:\/\/bioinformatics.babraham.ac.uk\/projects\/. 2010."},{"key":"e_1_2_10_59_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btu170"},{"key":"e_1_2_10_60_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.3317"},{"key":"e_1_2_10_60_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btu638"},{"key":"e_1_2_10_61_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0550-8"},{"key":"e_1_2_10_62_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv007"},{"key":"e_1_2_10_63_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.1239303"}],"container-title":["Advanced Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.202105909","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/advs.202105909","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.202105909","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T21:16:05Z","timestamp":1759785365000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/advs.202105909"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4,18]]},"references-count":82,"journal-issue":{"issue":"21","published-print":{"date-parts":[[2022,7]]}},"alternative-id":["10.1002\/advs.202105909"],"URL":"https:\/\/doi.org\/10.1002\/advs.202105909","archive":["Portico"],"relation":{},"ISSN":["2198-3844","2198-3844"],"issn-type":[{"value":"2198-3844","type":"print"},{"value":"2198-3844","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,4,18]]},"assertion":[{"value":"2021-12-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-04-18","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"2105909"}}