{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T02:17:10Z","timestamp":1789784230606,"version":"4.0.1"},"reference-count":96,"publisher":"Wiley","issue":"24","license":[{"start":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T00:00:00Z","timestamp":1778544000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T00:00:00Z","timestamp":1778544000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100018951","name":"Institut Pierre-Gilles de Gennes","doi-asserted-by":"publisher","award":["ANR\u201010\u2010EQPX\u201034"],"award-info":[{"award-number":["ANR\u201010\u2010EQPX\u201034"]}],"id":[{"id":"10.13039\/501100018951","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100014434","name":"Narodowa Agencja Wymiany Akademickiej","doi-asserted-by":"publisher","award":["PPI\/APM\/2019\/1\/00089\/U\/00001"],"award-info":[{"award-number":["PPI\/APM\/2019\/1\/00089\/U\/00001"]}],"id":[{"id":"10.13039\/501100014434","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Adv Healthcare Materials"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Physiologically relevant 3D tumor models incorporating extracellular matrix (ECM) and cancer\u2010associated fibroblasts (CAFs) are essential for studying tumor progression and drug resistance, yet often suffer from hydrogel contraction and instability\u2014especially in microfluidic formats, where ECM deformation hampers long\u2010term culture and quantitative imaging. Here, we present a microfluidic tumor\u2013fibroblast co\u2010culture platform for head and neck squamous cell carcinoma (HNSCC) that overcomes these limitations via a dual strategy: APTES\u2010mediated surface silanization anchors the ECM to the chip, combined with Genipin\u2010based crosslinking, which modestly increases hydrogel stiffness and progressively reinforces the network without compromising cell viability, as confirmed by time\u2010 and frequency\u2010resolved rheology. Fourier\u2010transform infrared spectroscopy (FTIR) verified successful collagen crosslinking while preserving reactive \u2500OH and \u2500NH\n                    <jats:sub>2<\/jats:sub>\n                    groups, enabling covalent bonding to the APTES\u2010functionalized chip. The platform further integrates semi\u2010automated segmentation and high\u2010content imaging to quantify dynamic phenotypic drug responses at both single\u2010cell and multicellular\/tissue organization levels. Drug chemosensitivity assays, including co\u2010culture with patient\u2010derived CAFs, enabled quantitative assessment of clinically relevant chemoprotective effects. By combining biomaterial engineering with functional microfluidic design, this system enables reproducible, physiologically relevant modeling of tumor\u2013fibroblast interactions, offering a scalable tool for preclinical drug chemosensitivity screening and clinical translation.\n                  <\/jats:p>","DOI":"10.1002\/adhm.202503566","type":"journal-article","created":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T04:50:14Z","timestamp":1778647814000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Genipin\u2010Crosslinked, Silane\u2010Anchored 3D Tumor\u2013Stroma Microtissues for High\u2010Content On\u2010Chip Drug Testing"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8662-5471","authenticated-orcid":false,"given":"Doriane","family":"Le Manach","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology Medical University of Lublin  Lublin Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2479-6392","authenticated-orcid":false,"given":"Reza","family":"Kowsari\u2010Esfahan","sequence":"additional","affiliation":[{"name":"Laboratoire De Biophysique et Evolution UMR CNRS\u2010ESPCI 8231 Chimie Biologie Innovation PSL University  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9735-9180","authenticated-orcid":false,"given":"Emilia","family":"Reszczy\u0144ska","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology Medical University of Lublin  Lublin Poland"},{"name":"Department of Plant Physiology and Biophysics Institute of Biological Sciences Faculty of Biology and Biotechnology Maria Curie\u2010Sk\u0142odowska University  Lublin Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3690-4610","authenticated-orcid":false,"given":"Philippe","family":"Nghe","sequence":"additional","affiliation":[{"name":"Laboratoire De Biophysique et Evolution UMR CNRS\u2010ESPCI 8231 Chimie Biologie Innovation PSL University  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9034-301X","authenticated-orcid":false,"given":"Matthias","family":"Nees","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology Medical University of Lublin  Lublin Poland"},{"name":"FICAN West Cancer Centre Laboratory, Cancer Research Unit, Institute of Biomedicine, Turku University Hospital University of Turku  Turku Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,12]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41415\u2010022\u20105166\u2010x"},{"issue":"3","key":"e_1_2_11_3_1","article-title":"Cancer Stem Cells in Head and Neck Cancer","volume":"10","author":"Picon H.","year":"2021","journal-title":"American Journal of Stem Cells"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419\u2010019\u20101769\u20109"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13045\u2010018\u20100578\u20104"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13578\u2010022\u201000887\u20103"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrclinonc.2017.166"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1158\/1535\u20107163.MCT\u201017\u20100733"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/adfm.201909032"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41416\u2010023\u201002186\u20101"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41368\u2010021\u201000131\u20107"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.10.044"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078\u20100432.CCR\u201020\u20104226"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2024.09.046"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature12626"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41420\u2010024\u201002053\u20109"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2011.07.001"},{"key":"e_1_2_11_18_1","first-page":"199","volume-title":"Biomaterial\u2010based Hydrogels: Therapeutics Carrier and Tissue Regeneration","author":"ID A.","year":"2024"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41556\u2010023\u201001272\u2010z"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/adfm.202000545"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.adg3840"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2024.122682"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.cellbio.042308.113318"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010020\u201018794\u2010x"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010025\u201092151\u20100"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.colsurfb.2016.11.011"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.5090\/kjtcs.2011.44.3.197"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1039\/D3NR01568H"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010022\u201030384\u20107"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202108427"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1007\/s44174\u2010024\u201000169\u20101"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12033\u2010022\u201000626\u20106"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers15225320"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/cam4.70240"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010019\u201047059\u2010x"},{"key":"e_1_2_11_36_1","unstructured":"Aivia 14\u2010Deeper Spatial Insights Powered by AI [accessed 9 September 2024]. Disponible sur:https:\/\/www.aivia\u2010software.com\/aivia14."},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.5046"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells14191543"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbm.a.31715"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10924\u2010023\u201002973\u20100"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbm.a.33006"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1017\/s0033583597003375"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/0277\u20105379(87)90444\u20105"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.1989.7.1.100"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00280\u2010023\u201004512\u2010z"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1002\/adhm.201700196"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1039\/D2BM00881E"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0159013"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.1177\/2041731420974861"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.1002\/jor.23483"},{"key":"e_1_2_11_51_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010023\u201045429\u20100"},{"key":"e_1_2_11_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2008.12.022"},{"key":"e_1_2_11_53_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10856\u2010016\u20105763\u20109"},{"key":"e_1_2_11_54_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41578\u2010020\u20100199\u20108"},{"key":"e_1_2_11_55_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.02605"},{"key":"e_1_2_11_56_1","doi-asserted-by":"publisher","DOI":"10.1039\/C8AN01216D"},{"key":"e_1_2_11_57_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.988502"},{"key":"e_1_2_11_58_1","doi-asserted-by":"publisher","DOI":"10.1002\/bit.28561"},{"key":"e_1_2_11_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2010.07.004"},{"key":"e_1_2_11_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2015.05.016"},{"key":"e_1_2_11_61_1","doi-asserted-by":"publisher","DOI":"10.1111\/1523\u20101747.ep12284425"},{"key":"e_1_2_11_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.08.006"},{"key":"e_1_2_11_63_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12967\u2010019\u20102058\u20101"},{"key":"e_1_2_11_64_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2016.02.031"},{"key":"e_1_2_11_65_1","doi-asserted-by":"publisher","DOI":"10.1186\/s42825\u2010024\u201000165\u20107"},{"key":"e_1_2_11_66_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2016.05.033"},{"key":"e_1_2_11_67_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12935\u2010023\u201002982\u2010y"},{"key":"e_1_2_11_68_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers12010092"},{"key":"e_1_2_11_69_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2012.08.007"},{"key":"e_1_2_11_70_1","doi-asserted-by":"publisher","DOI":"10.1080\/19336918.2015.1005469"},{"key":"e_1_2_11_71_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.matbio.2009.05.001"},{"key":"e_1_2_11_72_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2007.08.007"},{"key":"e_1_2_11_73_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0220019"},{"key":"e_1_2_11_74_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.11.010"},{"key":"e_1_2_11_75_1","doi-asserted-by":"publisher","DOI":"10.1089\/ten.TEA.2010.0297"},{"key":"e_1_2_11_76_1","doi-asserted-by":"publisher","DOI":"10.1088\/2057\u20101976\/2\/4\/047002"},{"key":"e_1_2_11_77_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.eye.6700751"},{"key":"e_1_2_11_78_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097\u20104636(19990915)46:4<520::AID\u2010JBM10>3.0.CO;2\u20109"},{"key":"e_1_2_11_79_1","doi-asserted-by":"publisher","DOI":"10.1007\/s42242\u2010021\u201000126\u20107"},{"key":"e_1_2_11_80_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymeth.2015.09.005"},{"key":"e_1_2_11_81_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbiomech.2013.09.029"},{"key":"e_1_2_11_82_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201302925"},{"key":"e_1_2_11_83_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsami.9b07912"},{"key":"e_1_2_11_84_1","doi-asserted-by":"publisher","DOI":"10.3389\/fbioe.2022.865014"},{"key":"e_1_2_11_85_1","doi-asserted-by":"publisher","DOI":"10.1021\/jp808145x"},{"key":"e_1_2_11_86_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eurpolymj.2013.02.032"},{"key":"e_1_2_11_87_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2013.08.029"},{"key":"e_1_2_11_88_1","doi-asserted-by":"publisher","DOI":"10.1111\/cas.13998"},{"key":"e_1_2_11_89_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00204\u2010021\u201003063\u20107"},{"key":"e_1_2_11_90_1","doi-asserted-by":"publisher","DOI":"10.1002\/adhm.202302436"},{"key":"e_1_2_11_91_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12964\u2010024\u201001884\u20104"},{"key":"e_1_2_11_92_1","doi-asserted-by":"publisher","DOI":"10.1039\/c8lc01250d"},{"key":"e_1_2_11_93_1","doi-asserted-by":"publisher","DOI":"10.1063\/5.0146000"},{"key":"e_1_2_11_94_1","doi-asserted-by":"publisher","DOI":"10.1038\/s43586\u2010022\u201000118\u20106"},{"key":"e_1_2_11_95_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.00128"},{"key":"e_1_2_11_96_1","doi-asserted-by":"publisher","DOI":"10.1177\/2472555219830087"},{"key":"e_1_2_11_97_1","doi-asserted-by":"publisher","DOI":"10.3109\/10409238.2015.1135868"}],"container-title":["Advanced Healthcare Materials"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/adhm.202503566","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/adhm.202503566","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/adhm.202503566","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T21:28:25Z","timestamp":1782509305000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/adhm.202503566"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,12]]},"references-count":96,"journal-issue":{"issue":"24","published-print":{"date-parts":[[2026,6]]}},"alternative-id":["10.1002\/adhm.202503566"],"URL":"https:\/\/doi.org\/10.1002\/adhm.202503566","archive":["Portico"],"relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2025.07.03.662913","asserted-by":"object"}]},"ISSN":["2192-2640","2192-2659"],"issn-type":[{"value":"2192-2640","type":"print"},{"value":"2192-2659","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,12]]},"assertion":[{"value":"2025-07-18","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-29","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-12","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e03566"}}