{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T08:13:26Z","timestamp":1793520806579,"version":"4.5.0"},"reference-count":30,"publisher":"Wiley","issue":"43","license":[{"start":{"date-parts":[[2021,9,5]],"date-time":"2021-09-05T00:00:00Z","timestamp":1630800000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","award":["310030\u2010133110"],"award-info":[{"award-number":["310030\u2010133110"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004359","name":"Vetenskapsr\u00e5det","doi-asserted-by":"publisher","award":["2019\u201001864"],"award-info":[{"award-number":["2019\u201001864"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004063","name":"Knut och Alice Wallenbergs Stiftelse","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004063","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Materials"],"published-print":{"date-parts":[[2021,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Design criteria for tissue\u2010engineered materials in regenerative medicine include robust biological effectiveness, off\u2010the\u2010shelf availability, and scalable manufacturing under standardized conditions. For bone repair, existing strategies rely on primary autologous cells, associated with unpredictable performance, limited availability and complex logistic. Here, a conceptual shift based on the manufacturing of devitalized human hypertrophic cartilage (HyC), as cell\u2010free material inducing bone formation by recapitulating the developmental process of endochondral ossification, is reported. The strategy relies on a customized human mesenchymal line expressing bone morphogenetic protein\u20102 (BMP\u20102), critically required for robust chondrogenesis and concomitant extracellular matrix (ECM) enrichment. Following apoptosis\u2010driven devitalization, lyophilization, and storage, the resulting off\u2010the\u2010shelf cartilage tissue exhibits unprecedented osteoinductive properties, unmatched by synthetic delivery of BMP\u20102 or by living engineered grafts. Scalability and pre\u2010clinical efficacy are demonstrated by bioreactor\u2010based production and subsequent orthotopic assessment. The findings exemplify the broader paradigm of programming human cell lines as biological factory units to engineer customized ECMs, designed to activate specific regenerative processes.<\/jats:p>","DOI":"10.1002\/adma.202103737","type":"journal-article","created":{"date-parts":[[2021,9,6]],"date-time":"2021-09-06T02:39:30Z","timestamp":1630895970000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":51,"title":["Manufacturing of Human Tissues as off\u2010the\u2010Shelf Grafts Programmed to Induce Regeneration"],"prefix":"10.1002","volume":"33","author":[{"given":"S\u00e9bastien","family":"Pigeot","sequence":"first","affiliation":[{"name":"Department of Biomedicine University Hospital Basel University of Basel  Basel 4031 Switzerland"},{"name":"Department of Biomedical Engineering University Hospital Basel University of Basel  Basel 4031 Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thibaut","family":"Klein","sequence":"additional","affiliation":[{"name":"Department of Biomedicine University Hospital Basel University of Basel  Basel 4031 Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabiana","family":"Gullotta","sequence":"additional","affiliation":[{"name":"Department of Biomedicine University Hospital Basel University of Basel  Basel 4031 Switzerland"},{"name":"Innovative Immunotherapies Unit Division of Immunology, Transplantation and Infectious Diseases San Raffaele Hospital Scientific Institute Vita\u2010Salute San Raffaele University  Milan 20132 Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven J.","family":"Dupard","sequence":"additional","affiliation":[{"name":"Laboratory for Cell, Tissue, and Organ Engineering Department of Clinical Sciences Lund University  Lund 221 84 Sweden"},{"name":"Wallenberg Center for Molecular Medicine Lund University  Lund 221 84 Sweden"},{"name":"Stem Cell Center Lund University  Lund 221 84 Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandro","family":"Garcia Garcia","sequence":"additional","affiliation":[{"name":"Laboratory for Cell, Tissue, and Organ Engineering Department of Clinical Sciences Lund University  Lund 221 84 Sweden"},{"name":"Wallenberg Center for Molecular Medicine Lund University  Lund 221 84 Sweden"},{"name":"Stem Cell Center Lund University  Lund 221 84 Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andres","family":"Garc\u00eda\u2010Garc\u00eda","sequence":"additional","affiliation":[{"name":"Department of Biomedicine University Hospital Basel University of Basel  Basel 4031 Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sujeethkumar","family":"Prithiviraj","sequence":"additional","affiliation":[{"name":"Laboratory for Cell, Tissue, and Organ Engineering Department of Clinical Sciences Lund University  Lund 221 84 Sweden"},{"name":"Wallenberg Center for Molecular Medicine Lund University  Lund 221 84 Sweden"},{"name":"Stem Cell Center Lund University  Lund 221 84 Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pilar","family":"Lorenzo","sequence":"additional","affiliation":[{"name":"Wallenberg Center for Molecular Medicine Lund University  Lund 221 84 Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miriam","family":"Filippi","sequence":"additional","affiliation":[{"name":"Department of Biomedicine University Hospital Basel University of Basel  Basel 4031 Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claude","family":"Jaquiery","sequence":"additional","affiliation":[{"name":"Department of Biomedicine University Hospital Basel University of Basel  Basel 4031 Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Loraine","family":"Kouba","sequence":"additional","affiliation":[{"name":"Department of Biomedicine University Hospital Basel University of Basel  Basel 4031 Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Adelaide","family":"Asnaghi","sequence":"additional","affiliation":[{"name":"Department of Biomedicine University Hospital Basel University of Basel  Basel 4031 Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deepak Bushan","family":"Raina","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences Orthopedics Lund University  Lund 221 84 Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boris","family":"Dasen","sequence":"additional","affiliation":[{"name":"Department of Biomedicine University Hospital Basel University of Basel  Basel 4031 Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanna","family":"Isaksson","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences Orthopedics Lund University  Lund 221 84 Sweden"},{"name":"Department of Biomedical Engineering Lund University  Lund 221 84 Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrik","family":"\u00d6nnerfjord","sequence":"additional","affiliation":[{"name":"Rheumatology and Molecular Skeletal Biology Department of Clinical Sciences Lund University  Lund 221 84 Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magnus","family":"T\u00e4gil","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences Orthopedics Lund University  Lund 221 84 Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Attilio","family":"Bondanza","sequence":"additional","affiliation":[{"name":"Innovative Immunotherapies Unit Division of Immunology, Transplantation and Infectious Diseases San Raffaele Hospital Scientific Institute Vita\u2010Salute San Raffaele University  Milan 20132 Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6493-0432","authenticated-orcid":false,"given":"Ivan","family":"Martin","sequence":"additional","affiliation":[{"name":"Department of Biomedicine University Hospital Basel University of Basel  Basel 4031 Switzerland"},{"name":"Department of Biomedical Engineering University Hospital Basel University of Basel  Basel 4031 Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7639-6844","authenticated-orcid":false,"given":"Paul E.","family":"Bourgine","sequence":"additional","affiliation":[{"name":"Department of Biomedicine University Hospital Basel University of Basel  Basel 4031 Switzerland"},{"name":"Laboratory for Cell, Tissue, and Organ Engineering Department of Clinical Sciences Lund University  Lund 221 84 Sweden"},{"name":"Wallenberg Center for Molecular Medicine Lund University  Lund 221 84 Sweden"},{"name":"Stem Cell Center Lund University  Lund 221 84 Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,9,5]]},"reference":[{"key":"e_1_2_8_1_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41578-020-0204-2"},{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41563-020-0786-5"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.abb6683"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3008558"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1089\/ten.teb.2009.0461"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2009.07.002"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature01657"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1220108110"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aav7756"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2018.07.004"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.201902295"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1411975111"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1247663"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(16)31658-0"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt0602-592"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2016.12"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.scr.2013.12.006"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2014.12.004"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2013.04.058"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1089\/ten.teb.2015.0357"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12891-018-2346-6"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/cpr.12653"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoto.2013.5669"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.8493529"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-06504-7"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aam8645"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt1049"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1093\/glycob\/cwg082"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1089\/ten.2006.12.2141"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2018.04.025"}],"container-title":["Advanced Materials"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/adma.202103737","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/adma.202103737","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/adma.202103737","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T11:58:14Z","timestamp":1759751894000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/adma.202103737"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9,5]]},"references-count":30,"journal-issue":{"issue":"43","published-print":{"date-parts":[[2021,10]]}},"alternative-id":["10.1002\/adma.202103737"],"URL":"https:\/\/doi.org\/10.1002\/adma.202103737","archive":["Portico"],"relation":{},"ISSN":["0935-9648","1521-4095"],"issn-type":[{"value":"0935-9648","type":"print"},{"value":"1521-4095","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,9,5]]},"assertion":[{"value":"2021-05-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-09-05","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"2103737"}}