{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T16:45:00Z","timestamp":1791823500724,"version":"4.3.4"},"reference-count":66,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T00:00:00Z","timestamp":1791763200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T00:00:00Z","timestamp":1791763200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32571580"],"award-info":[{"award-number":["32571580"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32301148"],"award-info":[{"award-number":["32301148"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2021YFF1000700"],"award-info":[{"award-number":["2021YFF1000700"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003453","name":"Natural Science Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2026A1515011988"],"award-info":[{"award-number":["2026A1515011988"]}],"id":[{"id":"10.13039\/501100003453","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004826","name":"Natural Science Foundation of Beijing Municipality","doi-asserted-by":"publisher","award":["L232145"],"award-info":[{"award-number":["L232145"]}],"id":[{"id":"10.13039\/501100004826","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Materials"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Oral tumors are not shaped by biochemical signals alone; they also evolve within mechanically active and thermally fluctuating microenvironments that critically regulate malignant progression, immune remodeling, and therapeutic resistance. Here, we develop a dynamic bioorthogonal organoid platform that couples a 3D\u2010printed photothermal elastic scaffold with an interpenetrating hydrogel network derived from decellularized oral mucosa extracellular matrix, enabling the reconstruction of in vivo\u2010like structural support, matrix\u2010derived biochemical cues, spatial cellular compartmentalization, and dynamic physical stimulation. Through click chemistry\u2010mediated cell anchorage and hydrogel encapsulation, oral cancer cells and macrophages are spatially organized into a compartmentalized cancer\u2013immune niche. Under cyclic mechanical stretch and near\u2010infrared\u2010triggered periodic photothermal stimulation, dynamic culture markedly enhances cancer cell proliferation and glycolytic reprogramming while concomitantly polarizing macrophages toward a pro\u2010tumoral M2 phenotype. In both monoculture and coculture settings, biochemical\u2013mechano\u2013thermal stimulation substantially increases cancer cell chemoresistance. Mechanistically, these biochemical\u2010physical cues activate stress\u2010adaptive and survival programs while enriching cancer stem\u2010like populations. In a xenograft mouse model exposed to in vivo biochemical, mechanical and thermal stimulation, dynamic conditioning markedly accelerates tumor progression, enhances metastatic potential, and confers pronounced chemoresistance. Together, this study establishes a biomimetic multicellular tumor platform for uncovering how dynamic biochemical\u2010physical cues orchestrate cancer\u2013immune crosstalk and therapeutic failure.<\/jats:p>","DOI":"10.1002\/adma.75347","type":"journal-article","created":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T15:50:55Z","timestamp":1791820255000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A 3D\u2010Printed Biochemical\u2013Mechano\u2013Thermally Responsive Multicellular Tumor Organoid Platform Decodes Biochemical\u2010Physical Regulation of Cancer\u2013Immune Crosstalk and Chemoresistance"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0334-3730","authenticated-orcid":false,"given":"Yurui","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering Xiangya School of Basic Medical Sciences Central South University  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Fu","sequence":"additional","affiliation":[{"name":"National Laboratory of Solid State Microstructures Collaborative Innovation Center of Advanced Microstructures Chemistry and Biomedicine Innovation Center College of Engineering and Applied Sciences Jiangsu Key Laboratory of Artificial Functional Materials Nanjing University  Nanjing China"},{"name":"Department of Stomatology The Fourth Affiliated Hospital of Nanjing Medical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kerong","family":"Chen","sequence":"additional","affiliation":[{"name":"National Laboratory of Solid State Microstructures Collaborative Innovation Center of Advanced Microstructures Chemistry and Biomedicine Innovation Center College of Engineering and Applied Sciences Jiangsu Key Laboratory of Artificial Functional Materials Nanjing University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youwen","family":"Yang","sequence":"additional","affiliation":[{"name":"Jiangxi Province Key Laboratory of Additive Manufacturing of Implantable Medical Device Jiangxi University of Science and Technology  Nanchang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xun","family":"Tang","sequence":"additional","affiliation":[{"name":"Jiangsu Institute of Cancer Research Jiangsu Key Laboratory of Molecular and Translational Cancer Research The Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaodi","family":"Li","sequence":"additional","affiliation":[{"name":"Center for Quantitative Systems Biology Department of Physics Hong Kong Baptist University  Hong Kong SAR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9059-2430","authenticated-orcid":false,"given":"Zhuxin","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering Xiangya School of Basic Medical Sciences Central South University  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8289-5968","authenticated-orcid":false,"given":"Sukun","family":"Tian","sequence":"additional","affiliation":[{"name":"Center of Digital Dentistry National Center for Stomatology Peking University School and Hospital of Stomatology NHC Key Laboratory of Digital Stomatology  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3424-5028","authenticated-orcid":false,"given":"Yuchun","family":"Sun","sequence":"additional","affiliation":[{"name":"Center of Digital Dentistry National Center for Stomatology Peking University School and Hospital of Stomatology NHC Key Laboratory of Digital Stomatology  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3453-9656","authenticated-orcid":false,"given":"Xinghai","family":"Ning","sequence":"additional","affiliation":[{"name":"National Laboratory of Solid State Microstructures Collaborative Innovation Center of Advanced Microstructures Chemistry and Biomedicine Innovation Center College of Engineering and Applied Sciences Jiangsu Key Laboratory of Artificial Functional Materials Nanjing University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,12]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceb.2024.102422"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/mco2.70496"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12943\u2010023\u201001744\u20108"},{"issue":"3","key":"e_1_2_9_5_1","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1016\/j.ccell.2023.02.016","article-title":"The Evolving Tumor Microenvironment: From Cancer Initiation to Metastatic Outgrowth","volume":"41","author":"Visser K. E.","year":"2023","journal-title":"Cancer Cell"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1485174"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms26146650"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40001\u2010022\u201000835\u20104"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010024\u201008087\u20104"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41568\u2010024\u201000706\u20106"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12935\u2010021\u201001853\u20108"},{"issue":"3","key":"e_1_2_9_12_1","first-page":"229","article-title":"Tumor Spheroids and Organoids as Preclinical Model Systems","volume":"33","author":"Baniahmad A.","year":"2021","journal-title":"Med Genet"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41580\u2010024\u201000767\u20103"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/s43556\u2010026\u201000436\u20101"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41568\u2010021\u201000366\u2010w"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1186\/s43556\u2010025\u201000396\u2010y"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2021.611115"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392\u2010025\u201002325\u20105"},{"key":"e_1_2_9_19_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.biopha.2024.116930","article-title":"Macrophage Polarization in the Tumor Microenvironment: Emerging Roles and Therapeutic Potentials","volume":"177","author":"Zhang W.","year":"2024","journal-title":"Biomedicine & Pharmacotherapy"},{"key":"e_1_2_9_20_1","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/j.bioactmat.2025.10.002","article-title":"3D Printed Flexible Composite Scaffold With Ultrasonic\u2010Driven Wireless Electrical Stimulation Promotes Neuro\u2010Vascularization for Critical\u2010Size Bone Defects Regeneration","volume":"56","author":"Xia Y.","year":"2026","journal-title":"Bioactive Materials"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010021\u201021325\u2010x"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsbiomaterials.4c01221"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/sus2.248"},{"key":"e_1_2_9_24_1","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1016\/j.bioactmat.2021.12.032","article-title":"D\u2010Printed NIR\u2010Responsive Shape Memory Polyurethane\/Magnesium Scaffolds With Tight\u2010Contact for Robust Bone Regeneration","volume":"16","author":"Zhang Y.","year":"2022","journal-title":"Bioactive Materials"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2023.108076"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202101295"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2019.119615"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010018\u201004699\u20103"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/adfm.202306208"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12935\u2010023\u201002943\u20105"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.oor.2024.100666"},{"issue":"1","key":"e_1_2_9_32_1","first-page":"S147","article-title":"Biocompatibility and Characterization of Polylactic Acid\/Styrene\u2010Ethylene\u2010Butylene\u2010Styrene Composites","volume":"26","author":"Tsou C. H.","year":"2015","journal-title":"Bio\u2010Medical Materials and Engineering"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2022.121825"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.9b04436"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202503698"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1039\/D5TB00277J"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja3002666"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11684\u2010021\u20100900\u20103"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.3390\/biom13040673"},{"issue":"24","key":"e_1_2_9_40_1","doi-asserted-by":"crossref","first-page":"31864","DOI":"10.1021\/acsami.4c08603","article-title":"Polydopamine Adhesion: Catechol, Amine, Dihydroxyindole, and Aggregation Dynamics","volume":"16","author":"Lim J.","year":"2024","journal-title":"ACS Applied Materials & Interfaces"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abb4696"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1902\/jop.2011.100573"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2007.03.013"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsami.0c22073"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.trac.2025.118557"},{"key":"e_1_2_9_46_1","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1038\/s43586-021-00028-z","article-title":"Bioorthogonal Chemistry","volume":"1","author":"Scinto S. L.","year":"2021","journal-title":"Nature Reviews Methods Primers"},{"issue":"13","key":"e_1_2_9_47_1","doi-asserted-by":"crossref","DOI":"10.1002\/advs.202416841","article-title":"A Spatially Distributed Microneedle System for Bioorthogonal T Cell\u2010Guided Cancer Therapy","volume":"12","author":"Li L.","year":"2025","journal-title":"Advanced Science"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.bioconjchem.4c00084"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41570\u2010019\u20100126\u2010y"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202401921"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1093\/rb\/rbad107"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1002\/adhm.202502107"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41578\u2010024\u201000672\u20103"},{"issue":"1","key":"e_1_2_9_54_1","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1038\/s41392-023-01452-1","article-title":"Macrophages in Immunoregulation and Therapeutics","volume":"8","author":"Chen S.","year":"2023","journal-title":"Signal Transduction and Targeted Therapy"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392\u2010024\u201002082\u2010x"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mam.2023.101205"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.1097\/00001622\u2010199311000\u201000014"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41580\u2010025\u201000890\u20109"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.7314\/APJCP.2013.14.10.5579"},{"key":"e_1_2_9_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmbbm.2026.107351"},{"key":"e_1_2_9_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2016.12.034"},{"key":"e_1_2_9_62_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2014.349"},{"key":"e_1_2_9_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cca.2019.01.011"},{"key":"e_1_2_9_64_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejcb.2025.151523"},{"key":"e_1_2_9_65_1","doi-asserted-by":"publisher","DOI":"10.1038\/s12276\u2010022\u201000863\u20104"},{"key":"e_1_2_9_66_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392\u2010025\u201002176\u20100"},{"key":"e_1_2_9_67_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41571\u2010025\u201001059\u20101"}],"container-title":["Advanced Materials"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/adma.75347","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/adma.75347","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/adma.75347","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T15:50:58Z","timestamp":1791820258000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/adma.75347"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,12]]},"references-count":66,"alternative-id":["10.1002\/adma.75347"],"URL":"https:\/\/doi.org\/10.1002\/adma.75347","archive":["Portico"],"relation":{},"ISSN":["0935-9648","1521-4095"],"issn-type":[{"value":"0935-9648","type":"print"},{"value":"1521-4095","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,12]]},"assertion":[{"value":"2026-07-30","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-05","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-12","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e75347"}}