{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T14:52:52Z","timestamp":1792162372569,"version":"4.4.0"},"reference-count":84,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T00:00:00Z","timestamp":1791504000000},"content-version":"vor","delay-in-days":8,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100020270","name":"Advanced Materials and Bioengineering Research","doi-asserted-by":"publisher","award":["12\/RC\/2278_P2"],"award-info":[{"award-number":["12\/RC\/2278_P2"]}],"id":[{"id":"10.13039\/501100020270","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Biomedical Materials Res"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Articular cartilage (AC) regeneration remains a major challenge in musculoskeletal tissue engineering. Cartilage extracellular matrix (ECM)\u2010derived scaffolds have shown promise as tissue\u2010specific biomaterials, but the extent to which the fabrication process can be tuned to modulate scaffold pore architecture and mechanics and how this might influence the chondrogenic differentiation of mesenchymal stromal\/stem cells (MSCs) remains incompletely defined. The aim of this study was to develop solubilized porcine AC\u2010ECM scaffolds with controlled differences in pore size and matrix stiffness, and to evaluate how these factors regulate chondrogenesis of MSCs. Scaffolds with different pore sizes were fabricated by modifying the freezing cycle during lyophilization through the inclusion of an annealing step, while scaffold stiffness was varied by adjusting the AC\u2010ECM concentration from 10 (1% ECM) to 50\u2009mg\/mL (5% ECM). Incorporation of an annealing step led to a ~2.5\u2010fold increase in the mean scaffold pore size and was associated with improved construct elasticity and greater early cellular penetration. Increasing the AC\u2010ECM concentration increased scaffold stiffness, with the ramp modulus increasing from approximately 5\u2009kPa in the 1% scaffolds to approximately 60\u2009kPa in the 5% scaffolds. All scaffold groups supported cartilage\u2010matrix deposition during chondrogenic culture. Higher ECM concentrations were associated with greater total collagen accumulation, while the stiffest 5% scaffolds supported increased Type X collagen staining relative to the softer scaffolds. The expression of key chondrogenic genes\n                    <jats:italic>SOX9<\/jats:italic>\n                    ,\n                    <jats:italic>ACAN<\/jats:italic>\n                    , and\n                    <jats:italic>COL2A1<\/jats:italic>\n                    was higher in the 2% scaffolds compared to 5% scaffolds, while the expression of the hypertrophic marker\n                    <jats:italic>COL10A1<\/jats:italic>\n                    was higher in the 5% scaffolds. In summary, scaffold processing provided a practical means to tune pore architecture and bulk mechanical behavior in solubilized AC\u2010ECM scaffolds, and these differences were associated with changes in cell distribution and phenotype. These findings can potentially be leveraged to engineer scaffolds supportive of zonal cartilage tissue engineering or for osteochondral defect repair.\n                  <\/jats:p>","DOI":"10.1002\/jbm.a.70153","type":"journal-article","created":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T07:59:44Z","timestamp":1791532784000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Porosity and Stiffness of Articular Cartilage Extracellular Matrix Derived Scaffolds Modulate Chondrogenesis of Mesenchymal Stromal Cells"],"prefix":"10.1002","volume":"114","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9070-7290","authenticated-orcid":false,"given":"Giovanni","family":"Gonnella","sequence":"first","affiliation":[{"name":"Trinity Centre for Biomedical Engineering, Trinity Biomedical Sciences Institute Trinity College Dublin  Dublin Ireland"},{"name":"Department of Mechanical, Manufacturing and Biomedical Engineering School of Engineering, Trinity College Dublin  Dublin Ireland"},{"name":"Advanced Materials and Bioengineering Research Centre (AMBER) Royal College of Surgeons in Ireland and Trinity College Dublin  Dublin Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8114-0595","authenticated-orcid":false,"given":"Tosca","family":"Roncada","sequence":"additional","affiliation":[{"name":"Trinity Centre for Biomedical Engineering, Trinity Biomedical Sciences Institute Trinity College Dublin  Dublin Ireland"},{"name":"Department of Mechanical, Manufacturing and Biomedical Engineering School of Engineering, Trinity College Dublin  Dublin Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4091-0992","authenticated-orcid":false,"given":"Daniel J.","family":"Kelly","sequence":"additional","affiliation":[{"name":"Trinity Centre for Biomedical Engineering, Trinity Biomedical Sciences Institute Trinity College Dublin  Dublin Ireland"},{"name":"Department of Mechanical, Manufacturing and Biomedical Engineering School of Engineering, Trinity College Dublin  Dublin Ireland"},{"name":"Advanced Materials and Bioengineering Research Centre (AMBER) Royal College of Surgeons in Ireland and Trinity College Dublin  Dublin Ireland"},{"name":"Department of Anatomy and Regenerative Medicine Royal College of Surgeons in Ireland  Dublin Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,9]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1089\/ten.TEC.2019.0116"},{"key":"e_1_2_10_3_1","first-page":"487","article-title":"Articular Cartilage: Degeneration and Osteoarthritis, Repair, Regeneration, and Transplantation","volume":"47","author":"Buckwalter J. A.","year":"1998","journal-title":"Instructional Course Lectures"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749\u20106632.2009.05240.x"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/life12070982"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00167\u2010008\u20100663\u20102"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/biomimetics8010087"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/term.37"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00167\u2010011\u20101655\u20101"},{"key":"e_1_2_10_10_1","volume-title":"Osteochondral Tissue Engineering: Challenges, Current Strategies, and Technological Advances. Advances in Experimental Medicine and Biology","author":"Oliveira J. M.","year":"2018"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioactmat.2021.05.011"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines10092307"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.3390\/polym13040599"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mbm.2023.100007"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mtbio.2022.100343"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/rb\/rbae008"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biotechadv.2019.107421"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010022\u201029279\u20104"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2016.03.008"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2014.05.030"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1089\/ten.tea.2008.0253"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2016.04.019"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2016.08.005"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2008.01.037"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1089\/ten.TEA.2015.0546"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2018.09.044"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1089\/ten.TEA.2014.0117"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2016.07.034"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a025676"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.3390\/app10103435"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10439\u2010014\u20101103\u20108"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/dvdy.24379"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.3390\/ma16124425"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.3390\/ma10060568"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsami.8b10926"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2022.03.009"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1089\/ten.tec.2009.0422"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbm.1028"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.btre.2016.09.001"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2021.05.011"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41584\u2010018\u20100151\u20100"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2018.10.005"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.matbio.2014.08.009"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1002\/anbr.202100116"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmbbm.2016.04.022"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1039\/D1MA01166A"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.3390\/polym13132041"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1039\/C5TB02077H"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1609731113"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1002\/jor.22374"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2006.06.044"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40883\u2010021\u201000199\u2010x"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2010.11.065"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010017\u201001938\u20103"},{"key":"e_1_2_10_55_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbm.a.36731"},{"key":"e_1_2_10_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsamd.2021.04.002"},{"key":"e_1_2_10_57_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj1610303"},{"key":"e_1_2_10_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/s1570\u20100232(03)00158\u20102"},{"key":"e_1_2_10_59_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010017\u201017286\u20101"},{"key":"e_1_2_10_60_1","doi-asserted-by":"publisher","DOI":"10.1089\/ten.tea.2015.0339"},{"key":"e_1_2_10_61_1","doi-asserted-by":"publisher","DOI":"10.22203\/eCM.v038a12"},{"key":"e_1_2_10_62_1","doi-asserted-by":"publisher","DOI":"10.1002\/term.2199"},{"key":"e_1_2_10_63_1","doi-asserted-by":"publisher","DOI":"10.1385\/1\u201059259\u2010428\u2010x:217"},{"key":"e_1_2_10_64_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbm.b.34093"},{"key":"e_1_2_10_65_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmbbm.2011.11.009"},{"key":"e_1_2_10_66_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioactmat.2021.12.005"},{"key":"e_1_2_10_67_1","doi-asserted-by":"publisher","DOI":"10.3390\/bioengineering4030066"},{"issue":"4","key":"e_1_2_10_68_1","first-page":"349","article-title":"Occupational Allergy to Aldehydes in Health Care Workers. Clinical Observations. Experiments","volume":"11","author":"Kie\u0107\u2010Swierczy\u0144ska M.","year":"1998","journal-title":"International Journal of Occupational Medicine and Environmental Health"},{"key":"e_1_2_10_69_1","doi-asserted-by":"publisher","DOI":"10.1557\/s43580\u2010024\u201000930\u20100"},{"key":"e_1_2_10_70_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fbio.2024.104343"},{"key":"e_1_2_10_71_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2003.09.102"},{"key":"e_1_2_10_72_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep30854"},{"key":"e_1_2_10_73_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010020\u201064917\u20101"},{"key":"e_1_2_10_74_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bsbt.2016.02.004"},{"key":"e_1_2_10_75_1","doi-asserted-by":"publisher","DOI":"10.3390\/healthcare12161648"},{"key":"e_1_2_10_76_1","doi-asserted-by":"publisher","DOI":"10.1002\/jor.24426"},{"key":"e_1_2_10_77_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2022.02.032"},{"key":"e_1_2_10_78_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13287\u2010015\u20100083\u20104"},{"key":"e_1_2_10_79_1","doi-asserted-by":"publisher","DOI":"10.1039\/D2BM01980A"},{"key":"e_1_2_10_80_1","doi-asserted-by":"publisher","DOI":"10.1039\/D0TB02008G"},{"key":"e_1_2_10_81_1","doi-asserted-by":"publisher","DOI":"10.3389\/fbioe.2020.00373"},{"key":"e_1_2_10_82_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2012.09.052"},{"key":"e_1_2_10_83_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13770\u2010018\u20100135\u20109"},{"key":"e_1_2_10_84_1","doi-asserted-by":"publisher","DOI":"10.1002\/adhm.201400165"},{"key":"e_1_2_10_85_1","doi-asserted-by":"publisher","DOI":"10.1039\/D6TB00068A"}],"container-title":["Journal of Biomedical Materials Research Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jbm.a.70153","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jbm.a.70153","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jbm.a.70153","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T14:39:18Z","timestamp":1792161558000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jbm.a.70153"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10]]},"references-count":84,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2026,10]]}},"alternative-id":["10.1002\/jbm.a.70153"],"URL":"https:\/\/doi.org\/10.1002\/jbm.a.70153","archive":["Portico"],"relation":{},"ISSN":["1549-3296","1552-4965"],"issn-type":[{"value":"1549-3296","type":"print"},{"value":"1552-4965","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10]]},"assertion":[{"value":"2026-05-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-25","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-09","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70153"}}