{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T10:57:43Z","timestamp":1781175463607,"version":"3.54.1"},"reference-count":73,"publisher":"SAGE Publications","issue":"1","license":[{"start":{"date-parts":[[2022,1,1]],"date-time":"2022-01-01T00:00:00Z","timestamp":1640995200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["CARTILAGE"],"published-print":{"date-parts":[[2022,1]]},"abstract":"<jats:sec>\n                    <jats:title>Objective:<\/jats:title>\n                    <jats:p>Tissue-engineered cartilage implants must withstand the potential inflammatory and joint loading environment for successful long-term repair of defects. The work\u2019s objectives were to develop a novel, direct cartilage-macrophage co-culture system and to characterize interactions between self-assembled neocartilage and differentially stimulated macrophages.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design:<\/jats:title>\n                    <jats:p>In study 1, it was hypothesized that the proinflammatory response of macrophages would intensify with increasing construct stiffness; it was expected that the neocartilage would display a decrease in mechanical properties after co-culture. In study 2, it was hypothesized that bioactive factors would protect neocartilage properties during macrophage co-culture. Also, it was hypothesized that interleukin 10 (IL-10)-stimulated macrophages would improve neocartilage mechanical properties compared to lipopolysaccharide (LPS)-stimulated macrophages.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>As hypothesized, stiffer neocartilage elicited a heightened proinflammatory macrophage response, increasing tumor necrosis factor alpha (TNF-\u03b1) secretion by 5.47 times when LPS-stimulated compared to construct-only controls. Interestingly, this response did not adversely affect construct properties for the stiffest neocartilage but did correspond to a significant decrease in aggregate modulus for soft and medium stiffness constructs. In addition, bioactive factor-treated constructs were protected from macrophage challenge compared to chondrogenic medium-treated constructs, but IL-10 did not improve neocartilage properties, although stiff constructs appeared to bolster the anti-inflammatory nature of IL-10-stimulated macrophages. However, co-culture of bioactive factor-treated constructs with LPS-treated macrophages reduced TNF-\u03b1 secretion by over 4 times compared to macrophage-only controls.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>In conclusion, neocartilage stiffness can mediate macrophage behavior, but stiffness and bioactive factors prevent macrophage-induced degradation. Ultimately, this co-culture system could be utilized for additional studies to develop the burgeoning field of cartilage mechano-immunology.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/19476035221081466","type":"journal-article","created":{"date-parts":[[2022,3,22]],"date-time":"2022-03-22T00:50:48Z","timestamp":1647910248000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":10,"title":["Stiffness- and Bioactive Factor-Mediated Protection of Self-Assembled Cartilage against Macrophage Challenge in a Novel Co-Culture System"],"prefix":"10.1177","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0542-1034","authenticated-orcid":false,"given":"Ryan P.","family":"Donahue","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering, University of California, Irvine, Irvine, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9108-1456","authenticated-orcid":false,"given":"Jarrett M.","family":"Link","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, University of California, Irvine, Irvine, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vijaykumar S.","family":"Meli","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, University of California, Irvine, Irvine, CA, USA"},{"name":"The Edwards Lifesciences Center for Advanced Cardiovascular Technology, University of California, Irvine, Irvine, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jerry C.","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, University of California, Irvine, Irvine, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wendy F.","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, University of California, Irvine, Irvine, CA, USA"},{"name":"The Edwards Lifesciences Center for Advanced Cardiovascular Technology, University of California, Irvine, Irvine, CA, USA"},{"name":"Department of Chemical and Biomolecular Engineering, University of California, Irvine, Irvine, CA, USA"},{"name":"Department of Molecular Biology and Biochemistry, University of California, Irvine, Irvine, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5387-8405","authenticated-orcid":false,"given":"Kyriacos A.","family":"Athanasiou","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, University of California, Irvine, Irvine, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2022,3,21]]},"reference":[{"key":"bibr1-19476035221081466","doi-asserted-by":"publisher","DOI":"10.1017\/S1462399411001943"},{"key":"bibr2-19476035221081466","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2011.00052"},{"issue":"1","key":"bibr3-19476035221081466","volume":"12","author":"Chen Y","year":"2020","journal-title":"Am J Transl Res"},{"key":"bibr4-19476035221081466","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0196779"},{"key":"bibr5-19476035221081466","doi-asserted-by":"publisher","DOI":"10.1038\/s41536-021-00173-9"},{"key":"bibr6-19476035221081466","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2015.05.025"},{"key":"bibr7-19476035221081466","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2004.09.015"},{"key":"bibr8-19476035221081466","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-032712-095906"},{"key":"bibr9-19476035221081466","doi-asserted-by":"publisher","DOI":"10.12703\/P6-13"},{"key":"bibr10-19476035221081466","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.173.1.360"},{"key":"bibr11-19476035221081466","doi-asserted-by":"publisher","DOI":"10.1084\/jem.174.6.1549"},{"key":"bibr12-19476035221081466","doi-asserted-by":"publisher","DOI":"10.1115\/1.4042201"},{"key":"bibr13-19476035221081466","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2018.12.007"},{"key":"bibr14-19476035221081466","doi-asserted-by":"publisher","DOI":"10.1038\/s41584-019-0255-1"},{"key":"bibr15-19476035221081466","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.00111"},{"key":"bibr16-19476035221081466","doi-asserted-by":"publisher","DOI":"10.1039\/C6BM00068A"},{"key":"bibr17-19476035221081466","unstructured":"Centers for Disease Control and Prevention. Osteoarthritis; 2020. Available from: https:\/\/www.cdc.gov\/arthritis\/basics\/osteoarthritis.htm."},{"key":"bibr18-19476035221081466","unstructured":"Centers for Disease Control and Prevention. Arthritis related statistics; 2018. Available from: https:\/\/www.cdc.gov\/arthritis\/data_statistics\/arthritis-related-stats.htm."},{"key":"bibr19-19476035221081466","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2016.07.018"},{"key":"bibr20-19476035221081466","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2008.10.012"},{"key":"bibr21-19476035221081466","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2016.06.016"},{"key":"bibr22-19476035221081466","doi-asserted-by":"publisher","DOI":"10.1002\/JLB.MR0318-126R"},{"key":"bibr23-19476035221081466","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0041024"},{"key":"bibr24-19476035221081466","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2019.02.048"},{"key":"bibr25-19476035221081466","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-23482-5"},{"key":"bibr26-19476035221081466","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abb8471"},{"key":"bibr27-19476035221081466","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a025668"},{"key":"bibr28-19476035221081466","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2014.04.083"},{"key":"bibr29-19476035221081466","doi-asserted-by":"publisher","DOI":"10.1021\/acs.biomac.8b00444"},{"key":"bibr30-19476035221081466","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0145813"},{"key":"bibr31-19476035221081466","unstructured":"Food and Drug Administration. Guidance for industry: preparation of IDEs and INDs for products intended to repair or replace knee cartilage; 2011. Available from: https:\/\/www.fda.gov\/regulatory-information\/search-fda-guidance-documents\/preparation-ides-and-inds-products-intended-repair-or-replace-knee-cartilage."},{"issue":"4","key":"bibr32-19476035221081466","volume":"36","author":"Panepinto LM","year":"1986","journal-title":"Lab Anim Sci"},{"key":"bibr33-19476035221081466","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2015.00293"},{"key":"bibr34-19476035221081466","doi-asserted-by":"publisher","DOI":"10.1089\/ten.tec.2017.0109"},{"key":"bibr35-19476035221081466","doi-asserted-by":"publisher","DOI":"10.1258\/la.2007.06029e"},{"key":"bibr36-19476035221081466","doi-asserted-by":"publisher","DOI":"10.1089\/ten.tec.2017.0149"},{"key":"bibr37-19476035221081466","doi-asserted-by":"publisher","DOI":"10.1002\/term.2630"},{"key":"bibr38-19476035221081466","doi-asserted-by":"publisher","DOI":"10.1089\/ten.tea.2017.0136"},{"key":"bibr39-19476035221081466","doi-asserted-by":"publisher","DOI":"10.1186\/ar4409"},{"key":"bibr40-19476035221081466","doi-asserted-by":"publisher","DOI":"10.1002\/stem.1890"},{"key":"bibr41-19476035221081466","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0056983"},{"key":"bibr42-19476035221081466","doi-asserted-by":"publisher","DOI":"10.3727\/096368913X676204"},{"key":"bibr43-19476035221081466","doi-asserted-by":"publisher","DOI":"10.1088\/1758-5090\/abd9d9"},{"key":"bibr44-19476035221081466","doi-asserted-by":"publisher","DOI":"10.1089\/ten.2006.12.969"},{"key":"bibr45-19476035221081466","doi-asserted-by":"publisher","DOI":"10.1002\/term.2791"},{"key":"bibr46-19476035221081466","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aaq1802"},{"key":"bibr47-19476035221081466","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0217183"},{"key":"bibr48-19476035221081466","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.715894"},{"key":"bibr49-19476035221081466","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.15669"},{"key":"bibr50-19476035221081466","doi-asserted-by":"publisher","DOI":"10.1063\/1.5067301"},{"key":"bibr51-19476035221081466","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2016.09.024"},{"key":"bibr52-19476035221081466","doi-asserted-by":"publisher","DOI":"10.1089\/ten.tec.2016.0184"},{"key":"bibr53-19476035221081466","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetimm.2018.04.002"},{"key":"bibr54-19476035221081466","doi-asserted-by":"publisher","DOI":"10.1039\/D1BM00746G"},{"key":"bibr55-19476035221081466","doi-asserted-by":"publisher","DOI":"10.1177\/1947603520918653"},{"key":"bibr56-19476035221081466","doi-asserted-by":"publisher","DOI":"10.1002\/adhm.201300532"},{"key":"bibr57-19476035221081466","doi-asserted-by":"publisher","DOI":"10.1089\/ten.tec.2017.0018"},{"key":"bibr58-19476035221081466","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0195261"},{"key":"bibr59-19476035221081466","volume":"316","author":"Athanasiou KA","year":"1995","journal-title":"Clin Orthop Relat Res"},{"key":"bibr60-19476035221081466","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2020.04.019"},{"key":"bibr61-19476035221081466","doi-asserted-by":"publisher","DOI":"10.1038\/nmat4917"},{"issue":"4","key":"bibr62-19476035221081466","volume":"39","author":"D\u0105browska AM","year":"2014","journal-title":"Cent Eur J Immunol"},{"key":"bibr63-19476035221081466","doi-asserted-by":"publisher","DOI":"10.1039\/c6ib00105j"},{"key":"bibr64-19476035221081466","doi-asserted-by":"publisher","DOI":"10.1002\/bit.22574"},{"key":"bibr65-19476035221081466","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2018.10.007"},{"key":"bibr66-19476035221081466","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-4827(03)00180-0"},{"issue":"6","key":"bibr67-19476035221081466","volume":"14","author":"Zhang Y","year":"2017","journal-title":"Exp Ther Med"},{"key":"bibr68-19476035221081466","doi-asserted-by":"publisher","DOI":"10.1007\/s11926-003-0081-x"},{"key":"bibr69-19476035221081466","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2007.03.090"},{"issue":"8","key":"bibr70-19476035221081466","volume":"104","author":"Albro Michael B","year":"2013","journal-title":"Biophys J"},{"key":"bibr71-19476035221081466","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.10561"},{"key":"bibr72-19476035221081466","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-49435-z"},{"key":"bibr73-19476035221081466","doi-asserted-by":"publisher","DOI":"10.1002\/jlb.66.3.391"}],"container-title":["CARTILAGE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/19476035221081466","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/19476035221081466","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/19476035221081466","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T14:01:21Z","timestamp":1777384881000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/19476035221081466"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1]]},"references-count":73,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2022,1]]}},"alternative-id":["10.1177\/19476035221081466"],"URL":"https:\/\/doi.org\/10.1177\/19476035221081466","relation":{},"ISSN":["1947-6035","1947-6043"],"issn-type":[{"value":"1947-6035","type":"print"},{"value":"1947-6043","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1]]},"article-number":"19476035221081466"}}