{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T08:00:41Z","timestamp":1785398441743,"version":"3.56.0"},"reference-count":46,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T00:00:00Z","timestamp":1783555200000},"content-version":"vor","delay-in-days":8,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000066","name":"National Institute of Environmental Health Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000066","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biotechnology Journal"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Tumor spheroids are widely used to model the tumor microenvironment and evaluate immune\u2010mediated cytotoxicity, but conventional methods such as ultralow\u2010attachment and hanging\u2010drop plates typically require 48\u201372\u00a0h to generate stable spheroids, limiting scalability and rapid testing. Here, we report a simple method for generating uniform tumor spheroids within 7\u20138\u00a0h using continuous rocking in standard multiwell plates. Computational fluid dynamics simulations showed that rocking produced mild oscillatory hydrodynamic conditions, with average shear stress ranging from 0.4 to 0.8\u00a0dyn\/cm\n                    <jats:sup>2<\/jats:sup>\n                    and X\u2010direction shear stress remaining near \u00b10.2\u00a0dyn\/cm\n                    <jats:sup>2<\/jats:sup>\n                    , promoting controlled cell aggregation while maintaining spheroid integrity. Using this approach, Hep3B cells reproducibly formed spheroids 80\u2013150\u00a0\u00b5m in diameter across multiple seeding densities, yielding thousands of spheroids per well. The spheroids were embedded in extracellular matrix and transferred to a 36PillarPlate for scalable 3D tumor\u2010immune coculture assays. To demonstrate utility, Hep3B spheroids were cocultured with NK\u201092 cells in the presence or absence of the immunomodulator berberine. Berberine treatment enhanced NK\u201092 localization and spheroid disruption, resulting in reduced tumor viability. This approach reduces spheroid preparation time from days to hours and enables same\u2010day integration into 3D assays, providing a practical platform for studying tumor\u2010immune interactions and screening immunomodulatory therapeutics.\n                  <\/jats:p>","DOI":"10.1002\/biot.70283","type":"journal-article","created":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T11:12:16Z","timestamp":1783595536000},"source":"Crossref","is-referenced-by-count":0,"title":["Rocking\u2010Induced Rapid Formation of Tumor Spheroids for Scalable 3D Tumor\u2010Immune Coculture Assays"],"prefix":"10.1002","volume":"21","author":[{"given":"Pranav","family":"Joshi","sequence":"first","affiliation":[{"name":"Bioprinting Laboratories Inc.  Dallas Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manav Goud","family":"Vanga","sequence":"additional","affiliation":[{"name":"Bioprinting Laboratories Inc.  Dallas Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charishma","family":"Jonnadula","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering University of North Texas  Denton Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minseong","family":"Lee","sequence":"additional","affiliation":[{"name":"Bioprinting Laboratories Inc.  Dallas Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria","family":"Gnenema","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering University of North Texas  Denton Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ananya","family":"Jamdagneya","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering University of North Texas  Denton Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sang\u2010Hyun","family":"Lee","sequence":"additional","affiliation":[{"name":"MBD Co. Ltd.  Suwon Gyeonggi\u2010do Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bosung","family":"Ku","sequence":"additional","affiliation":[{"name":"MBD Co. Ltd.  Suwon Gyeonggi\u2010do Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moo\u2010Yeal","family":"Lee","sequence":"additional","affiliation":[{"name":"Bioprinting Laboratories Inc.  Dallas Texas USA"},{"name":"Department of Biomedical Engineering University of North Texas  Denton Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,9]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2021.114003"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2020.101985"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2022.114365"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.27782"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41568\u2010022\u201000491\u20100"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1152\/physiol.00036.2016"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12935\u2010019\u20100733\u20101"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.trecan.2020.10.009"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.2147\/DDDT.S49584"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2021.03.076"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.603640"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.3389\/fbioe.2022.945149"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0264366"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1135148"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22041633"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1098\/rsif.2016.0649"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.73020"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.13857"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.2144\/btn\u20102020\u20100081"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers15041221"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/cam4.70239"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0194170"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsbiomaterials.4c00179"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/adhm.202302502"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.smim.2017.08.002"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2016.00091"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcyt.2022.12.003"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1700737"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12935\u2010023\u201003064\u20109"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules190812349"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1097\/CAD.0b013e328330d95b"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/aps.2016.125"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.3390\/ph16121652"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1002\/ptr.7407"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2019.03.024"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2013.1506"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.livres.2022.08.003"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1021\/la9907533"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1088\/1742\u20106596\/916\/1\/012038"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20174131"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbiotec.2010.01.012"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neo.2014.12.004"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaa6204"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.4161\/onci.28147"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1080\/14653240802301872"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1002\/bit.28924"}],"container-title":["Biotechnology 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