{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T04:27:28Z","timestamp":1787372848685,"version":"build-2736575974"},"reference-count":31,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T00:00:00Z","timestamp":1787184000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005090","name":"Beijing Nova Program","doi-asserted-by":"publisher","award":["202604841266"],"award-info":[{"award-number":["202604841266"]}],"id":[{"id":"10.13039\/501100005090","id-type":"DOI","asserted-by":"publisher"}]},{"award":["202604841266"],"award-info":[{"award-number":["202604841266"]}],"id":[{"id":"https:\/\/ror.org\/033pgsq69","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82574366"],"award-info":[{"award-number":["82574366"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82304442"],"award-info":[{"award-number":["82304442"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["22304099"],"award-info":[{"award-number":["22304099"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"award":["82574366"],"award-info":[{"award-number":["82574366"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"award":["82304442"],"award-info":[{"award-number":["82304442"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"award":["22304099"],"award-info":[{"award-number":["22304099"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key R&D Program of China","doi-asserted-by":"crossref","award":["2023YFC3504401"],"award-info":[{"award-number":["2023YFC3504401"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100012166","name":"National Key R&D Program of China","doi-asserted-by":"crossref","award":["2022YFA1103403"],"award-info":[{"award-number":["2022YFA1103403"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences","award":["2024-I2M-3-013"],"award-info":[{"award-number":["2024-I2M-3-013"]}]},{"name":"Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences","award":["2023-I2M-2-001"],"award-info":[{"award-number":["2023-I2M-2-001"]}]},{"award":["2024-I2M-3-013"],"award-info":[{"award-number":["2024-I2M-3-013"]}],"id":[{"id":"https:\/\/ror.org\/02drdmm93","id-type":"ROR","asserted-by":"publisher"}]},{"award":["2023-I2M-2-001"],"award-info":[{"award-number":["2023-I2M-2-001"]}],"id":[{"id":"https:\/\/ror.org\/02drdmm93","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004826","name":"Beijing Natural Science Foundation","doi-asserted-by":"publisher","award":["L256002"],"award-info":[{"award-number":["L256002"]}],"id":[{"id":"10.13039\/501100004826","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Young Elite Scientist Sponsorship Program of the Beijing Association for Science and Technology","award":["BYESS2023166"],"award-info":[{"award-number":["BYESS2023166"]}]},{"name":"Young Elite Scientist Sponsorship Program of the Beijing Association for Science and Technology","award":["BYESS2024140"],"award-info":[{"award-number":["BYESS2024140"]}]},{"award":["BYESS2023166"],"award-info":[{"award-number":["BYESS2023166"]}],"id":[{"id":"https:\/\/ror.org\/05w27xr10","id-type":"ROR","asserted-by":"publisher"}]},{"award":["BYESS2024140"],"award-info":[{"award-number":["BYESS2024140"]}],"id":[{"id":"https:\/\/ror.org\/05w27xr10","id-type":"ROR","asserted-by":"publisher"}]},{"name":"State Key Laboratory of Respiratory Health and Multimorbidity Special Fund","award":["2060204"],"award-info":[{"award-number":["2060204"]}]},{"name":"China Postdoctoral Science Foundation Funded Project","award":["2023T160372"],"award-info":[{"award-number":["2023T160372"]}]},{"name":"China Postdoctoral Science Foundation Funded Project","award":["2022M711779"],"award-info":[{"award-number":["2022M711779"]}]},{"name":"China Postdoctoral Science Foundation Funded Project","award":["BX20220160"],"award-info":[{"award-number":["BX20220160"]}]},{"award":["2023T160372"],"award-info":[{"award-number":["2023T160372"]}],"id":[{"id":"https:\/\/ror.org\/0426zh255","id-type":"ROR","asserted-by":"publisher"}]},{"award":["2022M711779"],"award-info":[{"award-number":["2022M711779"]}],"id":[{"id":"https:\/\/ror.org\/0426zh255","id-type":"ROR","asserted-by":"publisher"}]},{"award":["BX20220160"],"award-info":[{"award-number":["BX20220160"]}],"id":[{"id":"https:\/\/ror.org\/0426zh255","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Organoids-on-a-chip integrate the three-dimensional structural fidelity of organoids with the dynamic microenvironmental control capabilities of microfluidic technology, providing a transformative preclinical research platform for drug development. This perspective catalogues organoids-on-a-chip systems encompassing liver, heart, tumor, neural, tissue barrier, and multi-organ integration platforms, and elaborates on their distinctive advantages in dynamically simulating the complete in vivo trajectory of drug absorption, distribution, metabolism, target engagement, and toxicological response. The mechanisms of this technology overcome the limitations associated with conventional static culture models, and interspecies disparities are elucidated. Furthermore, the applications of these systems across critical stages of drug development are summarized, including preclinical safety assessment, integrated pharmacokinetic\/pharmacodynamic studies, personalized therapeutics, immunotherapy evaluation, and disease molecular mechanisms. Finally, we highlighted the main challenges facing this field and discussed future directions.<\/jats:p>","DOI":"10.3390\/ijms27167432","type":"journal-article","created":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T08:10:20Z","timestamp":1787213420000},"page":"7432","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Organoids-on-a-Chip: An Integrating New Technology for Drug Development"],"prefix":"10.3390","volume":"27","author":[{"given":"Mengqi","family":"He","sequence":"first","affiliation":[{"name":"MOE Key Laboratory of Precision Nutrition and Food Quality, Department of Nutrition and Health, China Agricultural University, Beijing 100193, China"},{"name":"State Key Laboratory of Respiratory Health and Multimorbidity, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing 100005, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuting","family":"Gong","sequence":"additional","affiliation":[{"name":"MOE Key Laboratory of Precision Nutrition and Food Quality, Department of Nutrition and Health, China Agricultural University, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinmei","family":"Xu","sequence":"additional","affiliation":[{"name":"MOE Key Laboratory of Precision Nutrition and Food Quality, Department of Nutrition and Health, China Agricultural University, Beijing 100193, China"},{"name":"MOE Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology, Department of Chemistry, Tsinghua University, Beijing 100084, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Menglin","family":"Hui","sequence":"additional","affiliation":[{"name":"MOE Key Laboratory of Precision Nutrition and Food Quality, Department of Nutrition and Health, China Agricultural University, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210098, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-5636-8770","authenticated-orcid":false,"given":"Yongjian","family":"Ai","sequence":"additional","affiliation":[{"name":"MOE Key Laboratory of Precision Nutrition and Food Quality, Department of Nutrition and Health, China Agricultural University, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1877","DOI":"10.1016\/j.cell.2026.02.012","article-title":"New approach methodologies for drug discovery","volume":"189","author":"Liu","year":"2026","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"7468","DOI":"10.1021\/acs.chemrev.0c01289","article-title":"Microfluidics for Drug Development: From Synthesis to Evaluation","volume":"121","author":"Liu","year":"2021","journal-title":"Chem. Rev."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1038\/s43586-022-00174-y","article-title":"Organoids","volume":"2","author":"Zhao","year":"2022","journal-title":"Nat. Rev. Methods Primers"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"960","DOI":"10.1126\/science.aaw7894","article-title":"Organoids-on-a-chip","volume":"364","author":"Park","year":"2019","journal-title":"Science"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"118518","DOI":"10.1016\/j.trac.2025.118518","article-title":"When microfluidics meets pharmaceutical analysis","volume":"194","author":"Ai","year":"2026","journal-title":"TrAC-Trend. Anal. Chem."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1126\/science.aeb0045","article-title":"Reimagining human-centric drug development with new approach methodologies","volume":"392","author":"Wu","year":"2016","journal-title":"Science"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1016\/j.chom.2021.04.002","article-title":"Organoids and organs-on-chips: Insights into human gut-microbe interactions","volume":"29","author":"Puschhof","year":"2021","journal-title":"Cell Host. Microbe"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1038\/s41580-020-0259-3","article-title":"Human organoids: Model systems for human biology and medicine","volume":"21","author":"Kim","year":"2020","journal-title":"Nat. Rev. Mol. Cell Bio."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1038\/s41568-018-0007-6","article-title":"Organoids in cancer research","volume":"18","author":"Drost","year":"2018","journal-title":"Nat. Rev. Cancer"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1038\/s43586-022-00118-6","article-title":"A guide to the organ-on-a-chip","volume":"2","author":"Leung","year":"2022","journal-title":"Nat. Rev. Methods Primers"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1038\/s44222-024-00163-8","article-title":"Microfluidic high-throughput 3D cell culture","volume":"2","author":"Ko","year":"2024","journal-title":"Nat. Rev. Bioeng."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1038\/s41573-020-0079-3","article-title":"Organs-on-chips: Into the next decade","volume":"20","author":"Low","year":"2020","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1038\/s41575-020-00386-1","article-title":"Human biomimetic liver microphysiology systems in drug development and precision medicine","volume":"18","author":"Gough","year":"2020","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1038\/s44222-023-00063-3","article-title":"Human disease models in drug development","volume":"1","author":"Loewa","year":"2023","journal-title":"Nat. Rev. Bioeng."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1038\/s41586-024-07204-7","article-title":"A patterned human neural tube model using microfluidic gradients","volume":"628","author":"Xue","year":"2024","journal-title":"Nature"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1038\/s41563-021-01057-5","article-title":"Next-generation cancer organoids","volume":"21","author":"LeSavage","year":"2021","journal-title":"Nat. Mater."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1331","DOI":"10.1158\/1538-7445.AM2024-1331","article-title":"MiNK-215, an IL-15 armored FAP-targeting CAR iNKT cell therapy, effectively treats human organoid models of treatment-refractory MSS colorectal cancer (CRC) liver metastases","volume":"84","author":"Krishnan","year":"2024","journal-title":"Cancer. Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"116790","DOI":"10.1016\/j.celrep.2025.116790","article-title":"A human tumor-immune organoid model of glioblastoma","volume":"45","author":"Baisiwala","year":"2026","journal-title":"Cell Rep."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1038\/s41578-021-00279-y","article-title":"Engineering organoids","volume":"6","author":"Hofer","year":"2021","journal-title":"Nat. Rev. Mater."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"4597","DOI":"10.1016\/j.cell.2021.08.005","article-title":"Organs-on-a-chip models for biological research","volume":"184","author":"Radisic","year":"2021","journal-title":"Cell"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1038\/s44222-024-00207-z","article-title":"Integrating organoids and organ-on-a-chip devices","volume":"2","author":"Zhao","year":"2024","journal-title":"Nat. Rev. Bioeng."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1038\/s41568-018-0104-6","article-title":"Modelling cancer in microfluidic human organs-on-chips","volume":"19","author":"Hassell","year":"2019","journal-title":"Nat. Rev. Cancer"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1192","DOI":"10.1039\/D2LC00804A","article-title":"Organoids\/organs-on-a-chip: New frontiers of intestinal pathophysiological models","volume":"23","author":"Wu","year":"2023","journal-title":"Lab Chip"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1038\/s41573-025-01317-y","article-title":"Human organoids as 3D in vitro platforms for drug discovery: Opportunities and challenges","volume":"25","author":"Wang","year":"2025","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"117905","DOI":"10.1016\/j.trac.2024.117905","article-title":"Trends in organ-on-a-chip for pharmacological analysis","volume":"180","author":"Xu","year":"2024","journal-title":"TrAC Trend Anal. Chem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1038\/s41573-025-01182-9","article-title":"Application of new approach methodologies for nonclinical safety assessment of drug candidates","volume":"24","author":"Beilmann","year":"2025","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1038\/s41551-019-0498-9","article-title":"Quantitative prediction of human pharmacokinetic responses to drugs via fluidically coupled vascularized organ chips","volume":"4","author":"Herland","year":"2020","journal-title":"Nat. Biomed. Eng."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1038\/s41587-019-0048-8","article-title":"Tubuloids derived from human adult kidney and urine for personalized disease modeling","volume":"37","author":"Schutgens","year":"2019","journal-title":"Nat. Biotechnol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1038\/s41586-020-2724-8","article-title":"Homeostatic mini-intestines through scaffold-guided organoid morphogenesis","volume":"585","author":"Nikolaev","year":"2020","journal-title":"Nature"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1038\/s43018-020-0102-y","article-title":"Applications of organoids for cancer biology and precision medicine","volume":"1","author":"Lo","year":"2020","journal-title":"Nat. Cancer"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"967","DOI":"10.1038\/s41551-024-01318-z","article-title":"A gut-on-a-chip incorporating human faecal samples and peristalsis predicts responses to immune checkpoint inhibitors for melanoma","volume":"9","author":"Ballerini","year":"2025","journal-title":"Nat. Biomed. Eng."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/16\/7432\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T04:12:19Z","timestamp":1787371939000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/16\/7432"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,20]]},"references-count":31,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["ijms27167432"],"URL":"https:\/\/doi.org\/10.3390\/ijms27167432","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,20]]}}}