{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T20:19:16Z","timestamp":1792181956120,"version":"4.4.0"},"reference-count":57,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,8,3]],"date-time":"2025-08-03T00:00:00Z","timestamp":1754179200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","award":["SNF 310\u00a0030_179\u00a0167"],"award-info":[{"award-number":["SNF 310\u00a0030_179\u00a0167"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Adv Funct Materials"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Endochondral ossification (ECO) is the process at the basis of long bone development, occurring in children and involving vascularization and subsequent mineralization of a cartilage template. Deregulated bone developmental pathways could correlate with pediatric bone tumors, including Ewing Sarcoma (EwS), an aggressive tumor with a poor prognosis for patients with recurrent or metastatic disease. Considering the limitations of available EwS preclinical models, at developing a microphysiological system recapitulating bone developmental steps are aimed, to investigate their influence on EwS cell proliferation and migratory behavior. This system includes spheroids of mesenchymal stromal cells sequentially differentiated in chondrogenic and hypertrophic stages within a fibrin hydrogel, in the presence or not of vascular cells and mineralized particles. It shows that by modulating system components it is possible to recapitulate hypertrophic ECO stage, in a higher extent with the addition of vascular cells without a mineral component. Hypertrophic conditions foster the proliferation of EwS cells as compared to avascular and mineralized environments and support the migration of highly aggressive EWSR1::FLI1\n                    <jats:sub>low<\/jats:sub>\n                    cell phenotype, contrarily to empty 3D fibrin gel. Overall, the results support the use of the ECO\u2010mimicking microphysiological system as a valuable preclinical model to investigate the role of developmental mechanisms in EwS onset and progression.\n                  <\/jats:p>","DOI":"10.1002\/adfm.202418470","type":"journal-article","created":{"date-parts":[[2025,8,4]],"date-time":"2025-08-04T06:31:55Z","timestamp":1754289115000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["A Vascularized Microphysiological System Reproducing Endochondral Ossification in Vitro to Study Ewing Sarcoma Proliferation and Migration"],"prefix":"10.1002","volume":"36","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6018-9920","authenticated-orcid":false,"given":"Maria Vittoria","family":"Colombo","sequence":"first","affiliation":[{"name":"Regenerative Medicine Division Institute for Translational Research Ente Ospedaliero Cantonale \u2010 Universit\u00e0 della Svizzera Italiana  via F Chiesa 5 Bellinzona 6500 Switzerland"},{"name":"Department of Chemistry Materials and Chemical Engineering G.Natta Politecnico di Milano  Piazzale Leonardo da Vinci 32 Milan 20100 Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6808-1642","authenticated-orcid":false,"given":"Chiara","family":"Arrigoni","sequence":"additional","affiliation":[{"name":"Regenerative Medicine Division Institute for Translational Research Ente Ospedaliero Cantonale \u2010 Universit\u00e0 della Svizzera Italiana  via F Chiesa 5 Bellinzona 6500 Switzerland"},{"name":"Euler Institute Biomedical Sciences Faculty Universit\u00e0 della Svizzera Italiana (USI)  via Buffi 13 Lugano 6900 Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5500-4987","authenticated-orcid":false,"given":"Tobias","family":"Faehling","sequence":"additional","affiliation":[{"name":"Hopp Children`s Cancer Center Heidelberg (KiTZ)  69120 Heidelberg Germany"},{"name":"Division of Translational Pediatric Sarcoma Research German Cancer Research Center (DKFZ) German Cancer Consortium (DKTK)  69120 Heidelberg Germany"},{"name":"National Center for Tumor Diseases (NCT) NCT Heidelberg, a partnership between DKFZ and Heidelberg University Hospital  69120 Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-1131-8439","authenticated-orcid":false,"given":"Antonietta","family":"Verrillo","sequence":"additional","affiliation":[{"name":"Regenerative Medicine Division Institute for Translational Research Ente Ospedaliero Cantonale \u2010 Universit\u00e0 della Svizzera Italiana  via F Chiesa 5 Bellinzona 6500 Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viviana","family":"Secci","sequence":"additional","affiliation":[{"name":"Regenerative Medicine Division Institute for Translational Research Ente Ospedaliero Cantonale \u2010 Universit\u00e0 della Svizzera Italiana  via F Chiesa 5 Bellinzona 6500 Switzerland"},{"name":"Department of Chemistry Materials and Chemical Engineering G.Natta Politecnico di Milano  Piazzale Leonardo da Vinci 32 Milan 20100 Italy"},{"name":"Euler Institute Biomedical Sciences Faculty Universit\u00e0 della Svizzera Italiana (USI)  via Buffi 13 Lugano 6900 Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0920-7377","authenticated-orcid":false,"given":"Thomas G. P.","family":"Gr\u00fcnewald","sequence":"additional","affiliation":[{"name":"Hopp Children`s Cancer Center Heidelberg (KiTZ)  69120 Heidelberg Germany"},{"name":"Division of Translational Pediatric Sarcoma Research German Cancer Research Center (DKFZ) German Cancer Consortium (DKTK)  69120 Heidelberg Germany"},{"name":"Institute of Pathology Heidelberg University Hospital  69120 Heidelberg Germany"},{"name":"National Center for Tumor Diseases (NCT) NCT Heidelberg, a partnership between DKFZ and Heidelberg University Hospital  69120 Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1976-5073","authenticated-orcid":false,"given":"Giuseppe","family":"Tal\u00f2","sequence":"additional","affiliation":[{"name":"Cell and Tissue Engineering Laboratory IRCCS Istituto Ortopedico Galeazzi  Via Cristina Belgioioso, 173 Milan 20161 Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Kummer","sequence":"additional","affiliation":[{"name":"Hopp Children`s Cancer Center Heidelberg (KiTZ)  69120 Heidelberg Germany"},{"name":"Division of Translational Pediatric Sarcoma Research German Cancer Research Center (DKFZ) German Cancer Consortium (DKTK)  69120 Heidelberg Germany"},{"name":"National Center for Tumor Diseases (NCT) NCT Heidelberg, a partnership between DKFZ and Heidelberg University Hospital  69120 Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge","family":"Gonzalez","sequence":"additional","affiliation":[{"name":"Pediatric Institute of Southern Switzerland Ente Ospedaliero Cantonale  Bellinzona 6500 Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincenzo","family":"De Rosa","sequence":"additional","affiliation":[{"name":"Pediatric Institute of Southern Switzerland Ente Ospedaliero Cantonale  Bellinzona 6500 Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3543-981X","authenticated-orcid":false,"given":"Christian","family":"Candrian","sequence":"additional","affiliation":[{"name":"Euler Institute Biomedical Sciences Faculty Universit\u00e0 della Svizzera Italiana (USI)  via Buffi 13 Lugano 6900 Switzerland"},{"name":"Service of Orthopaedics and Traumatology Department of Surgery Ente Ospedaliero Cantonale  Via Tesserete 46 Lugano 6900 Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5252-789X","authenticated-orcid":false,"given":"Andrea","family":"Barbero","sequence":"additional","affiliation":[{"name":"Department of Biomedicine University Hospital Basel University of Basel  Hebelstrasse, 20 Basel 4031 Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0246-7179","authenticated-orcid":false,"given":"Florencia","family":"Cidre\u2010Aranaz","sequence":"additional","affiliation":[{"name":"Hopp Children`s Cancer Center Heidelberg (KiTZ)  69120 Heidelberg Germany"},{"name":"Division of Translational Pediatric Sarcoma Research German Cancer Research Center (DKFZ) German Cancer Consortium (DKTK)  69120 Heidelberg Germany"},{"name":"National Center for Tumor Diseases (NCT) NCT Heidelberg, a partnership between DKFZ and Heidelberg University Hospital  69120 Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7301-1208","authenticated-orcid":false,"given":"Matteo","family":"Moretti","sequence":"additional","affiliation":[{"name":"Regenerative Medicine Division Institute for Translational Research Ente Ospedaliero Cantonale \u2010 Universit\u00e0 della Svizzera Italiana  via F Chiesa 5 Bellinzona 6500 Switzerland"},{"name":"Euler Institute Biomedical Sciences Faculty Universit\u00e0 della Svizzera Italiana (USI)  via Buffi 13 Lugano 6900 Switzerland"},{"name":"Cell and Tissue Engineering Laboratory IRCCS Istituto Ortopedico Galeazzi  Via Cristina Belgioioso, 173 Milan 20161 Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,8,3]]},"reference":[{"key":"e_1_2_10_1_1","author":"Breeland G.","year":"2023","journal-title":"StatPearls"},{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2015.04.035"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2007.06.009"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1220108110"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2024.122471"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1000302107"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2474-12-31"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1089\/ten.tea.2015.0339"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-018-0003-x"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm10081685"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2012.10.004"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1993.tb06137.x"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2016.498"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-07-1761"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-16244-2"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0116627"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.9388"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsbiomaterials.9b01068"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1089\/ten.tea.2016.0369"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1089\/ten.tec.2016.0371"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2013.00230"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature01657"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.15283\/ijsc17015"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1017802"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2014.444"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0407788101"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.10677"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/sctm.18-0147"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2014.03.010"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.2217\/nnm-2015-0021"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1359\/jbmr.1998.13.12.1852"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/jor.24692"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2021.05.056"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1093\/jmicro\/dfaa047"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10456-022-09842-9"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2022.09.011"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1039\/C3IB40267C"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.17.4.2336"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.22136"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.2287"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12861-014-0036-7"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2017.05.045"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.3389\/fbioe.2021.661989"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-015-0270-3"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.22018"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-09-2795"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-07-0133"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3394"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.135188"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc1093"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.2470"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2022.1044707"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.18632\/aging.205337"},{"key":"e_1_2_10_54_1","first-page":"13","volume":"2022","author":"Li Y.","year":"2022","journal-title":"Oxid. Med. Cell. Longevity"},{"key":"e_1_2_10_55_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep36639"},{"key":"e_1_2_10_56_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-08-2929"},{"key":"e_1_2_10_57_1","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2011.53"}],"container-title":["Advanced Functional Materials"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/adfm.202418470","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,10]],"date-time":"2026-01-10T15:17:03Z","timestamp":1768058223000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/adfm.202418470"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,3]]},"references-count":57,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2026,1]]}},"alternative-id":["10.1002\/adfm.202418470"],"URL":"https:\/\/doi.org\/10.1002\/adfm.202418470","archive":["Portico"],"relation":{},"ISSN":["1616-301X","1616-3028"],"issn-type":[{"value":"1616-301X","type":"print"},{"value":"1616-3028","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,3]]},"assertion":[{"value":"2024-09-30","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-03","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e18470"}}