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However, how to more accurately replicate the tumor microenvironment and implement high\u2010throughput drug screening on\u2010chip remains to be further explored. In this study, we developed a biomimetic intestinal tumor\u2010on\u2010a\u2010chip platform that simulates the 3D structure of intestinal crypts and villi, and incorporates a herringbone fluidic mixer. Compared to conventional chips, this design significantly improves the dynamic interplay between tumor cells and their surrounding microenvironment. Inside the chip, patient\u2010derived primary epithelial and tumor cells successfully form a 3D tumor model. Furthermore, the platform enables monitoring of dynamic drug response in tumor cells derived from individual patients. Preliminary findings indicate that mitophagy could be a key contributor to the development of chemoresistance. This biomimetic intestinal tumor\u2010on\u2010a\u2010chip platform effectively reproduces the complex characteristics of intestinal tumors through its high\u2010fidelity 3D structure and dynamic microenvironment.<\/jats:p>","DOI":"10.1002\/smll.202514836","type":"journal-article","created":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T09:36:06Z","timestamp":1776245766000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Biomimetic Human Intestinal Tumor\u2010on\u2010a\u2010Chip with Crypts and Villus\u2010Like Structures for Chemotherapy Drug Evaluations"],"prefix":"10.1002","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0113-3054","authenticated-orcid":false,"given":"Jianhua","family":"Lu","sequence":"first","affiliation":[{"name":"Department of Colorectal and Anal Surgery The First Affiliated Hospital of Wenzhou Medical University  Wenzhou China"},{"name":"Department of Gastrointestinal Surgery The Second Affiliated Hospital of Wenzhou Medical University  Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Colorectal and Anal Surgery The First Affiliated Hospital of Wenzhou Medical University  Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junqi","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Colorectal and Anal Surgery The First Affiliated Hospital of Wenzhou Medical University  Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luoran","family":"Shang","sequence":"additional","affiliation":[{"name":"Shanghai Xuhui Central Hospital Zhongshan\u2010Xuhui Hospital and the Shanghai Key Laboratory of Medical Epigenetics International Co\u2010laboratory of Medical Epigenetics and Metabolism (Ministry of Science and Technology Institutes of Biomedical Sciences) Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9242-4000","authenticated-orcid":false,"given":"Yuanjin","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Colorectal and Anal Surgery The First Affiliated Hospital of Wenzhou Medical University  Wenzhou China"},{"name":"School of Biological Science and Medical Engineering Southeast University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weijian","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Colorectal and Anal Surgery The First Affiliated Hospital of Wenzhou Medical University  Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,4,15]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(24)00360-X"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2025.9147"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202420586"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.analchem.8b05293"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-20-3665"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2025.11.044"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.34133\/research.0639"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/SMMD.20240009"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202210083"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/SMMD.20230028"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/smmd.136"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/SMMD.20230042"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1039\/D4BM01273A"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/SMMD.20230023"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s44286-024-00128-z"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2024.05.007"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s44286-023-00001-5"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202504647"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2724-8"},{"issue":"5","key":"e_1_2_9_21_1","first-page":"727","article-title":"Patient\u2010Derived Mini\u2010Colons Enable Long\u2010Term Modeling of Tumor\u2013Microenvironment Complexity","volume":"43","author":"Francisco L.\u2010M. 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