{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T02:59:38Z","timestamp":1784948378614,"version":"3.55.0"},"reference-count":66,"publisher":"Wiley","issue":"25","license":[{"start":{"date-parts":[[2023,3,18]],"date-time":"2023-03-18T00:00:00Z","timestamp":1679097600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Small"],"published-print":{"date-parts":[[2023,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The disruption of thyroid hormones because of chemical exposure is a significant societal problem. Chemical evaluations of environmental and human health risks are conventionally based on animal experiments. However, owing to recent breakthroughs in biotechnology, the potential toxicity of chemicals can now be evaluated using 3D cell cultures. In this study, the interactive effects of thyroid\u2010friendly soft (TS) microspheres on thyroid cell aggregates are elucidated and their potential as a reliable toxicity assessment tool is evaluated. Using state\u2010of\u2010the\u2010art characterization methods coupled with cell\u2010based analysis and quadrupole time\u2010of\u2010flight mass spectrometry, it is shown that TS\u2010microsphere\u2010integrated thyroid cell aggregates exhibit improved thyroid function. Specifically, the responses of zebrafish embryos, which are used for thyroid toxicity analysis, and the TS\u2010microsphere\u2010integrated cell aggregates to methimazole (MMI), a known thyroid inhibitor, are compared. The results show that the thyroid hormone disruption response of the TS\u2010microsphere\u2010integrated thyroid cell aggregates to MMI is more sensitive compared with those of the zebrafish embryos and conventionally formed cell aggregates. This proof\u2010of\u2010concept approach can be used to control cellular function in the desired direction and hence evaluate thyroid function. Thus, the proposed TS\u2010microsphere\u2010integrated cell aggregates may yield new fundamental insights for advancing in vitro cell\u2010based research.<\/jats:p>","DOI":"10.1002\/smll.202300236","type":"journal-article","created":{"date-parts":[[2023,3,18]],"date-time":"2023-03-18T10:24:31Z","timestamp":1679135071000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Thyroid\u2010Friendly Soft Materials as 3D Cell Culture Tool for Stimulating Thyroid Cell Function"],"prefix":"10.1002","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6496-5878","authenticated-orcid":false,"given":"Indong","family":"Jun","sequence":"first","affiliation":[{"name":"Environmental Safety Group Korea Institute of Science and Technology Europe (KIST\u2010EUROPE)  66123 Saarbr\u00fccken Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyunki","family":"Cho","sequence":"additional","affiliation":[{"name":"Environmental Safety Group Korea Institute of Science and Technology Europe (KIST\u2010EUROPE)  66123 Saarbr\u00fccken Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian E.","family":"Amos","sequence":"additional","affiliation":[{"name":"School of Human Sciences The University of Western Australia  Perth WA 6009 Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youngjun","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Cogno\u2010Mechatronics Engineering Pusan National University  Busan 46241 Republic of Korea"},{"name":"Department of Advanced Biomaterials Research Ceramics Materials Division, Korea Institute of Materials Science (KIMS)  Changwon 51508 Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu Suk","family":"Choi","sequence":"additional","affiliation":[{"name":"School of Human Sciences The University of Western Australia  Perth WA 6009 Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang Seon","family":"Ryu","sequence":"additional","affiliation":[{"name":"Environmental Safety Group Korea Institute of Science and Technology Europe (KIST\u2010EUROPE)  66123 Saarbr\u00fccken Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sang\u2010Ah","family":"Lee","sequence":"additional","affiliation":[{"name":"Environmental Safety Group Korea Institute of Science and Technology Europe (KIST\u2010EUROPE)  66123 Saarbr\u00fccken Germany"},{"name":"Office of Islands and Coastal Biology Research Honam National Institute of Biological Resources (HNIBR)  Mokpo 58792 Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong\u2010Wook","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Cogno\u2010Mechatronics Engineering Pusan National University  Busan 46241 Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyung\u2010Seop","family":"Han","sequence":"additional","affiliation":[{"name":"Center for Biomaterials Biomedical Research Institute Korea Institute of Science and Technology (KIST)  Seoul 02792 Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji Hun","family":"Yang","sequence":"additional","affiliation":[{"name":"Next &amp; Bio Inc. Seoul National University  Seoul 08826 Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyun\u2010Woo","family":"Jeong","sequence":"additional","affiliation":[{"name":"Single Cell Multiomics Laboratory Max\u2010Planck\u2010Institute for Molecular Biomedicine  48149 M\u00fcnster Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Honghyun","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Advanced Biomaterials Research Ceramics Materials Division, Korea Institute of Materials Science (KIMS)  Changwon 51508 Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2605-0922","authenticated-orcid":false,"given":"Young Jun","family":"Kim","sequence":"additional","affiliation":[{"name":"Environmental Safety Group Korea Institute of Science and Technology Europe (KIST\u2010EUROPE)  66123 Saarbr\u00fccken Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,3,18]]},"reference":[{"key":"e_1_2_8_1_1","doi-asserted-by":"publisher","DOI":"10.1787\/9789264311718-en"},{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrp.2021.100515"},{"key":"e_1_2_8_3_1","first-page":"653","volume":"38","author":"Knight J.","year":"2021","journal-title":"ALTEX"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.365.6459.1231"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/smll.202007628"},{"key":"e_1_2_8_6_1","volume-title":"The European Environment: State and Outlook 2020: Knowledge for Transition to a Sustainable Europe","author":"Agency E. E.","year":"2019"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1289\/EHP5297"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ecoenv.2021.112136"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12020-019-02025-5"},{"key":"e_1_2_8_10_1","first-page":"1","volume-title":"Thyroid Diseases: Pathogenesis, Diagnosis and Treatment","author":"Visser T. J.","year":"2018"},{"key":"e_1_2_8_11_1","unstructured":"OECD Test No. 408: Repeated Dose 90\u2010Day Oral Toxicity Study in Rodents 2018."},{"key":"e_1_2_8_12_1","unstructured":"OECD Test No. 421: Reproduction\/Developmental Toxicity Screening Test 2016."},{"key":"e_1_2_8_13_1","unstructured":"OECD Test No. 422: Combined Repeated Dose Toxicity Study with the Reproduction\/Developmental Toxicity Screening Test 2016."},{"key":"e_1_2_8_14_1","unstructured":"OECD Test No. 443: Extended One\u2010Generation Reproductive Toxicity Study 2018."},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/smll.202006252"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.trac.2016.04.014"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-020-0259-3"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1039\/C8MH00803E"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/stem.1499"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/smll.201901920"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/smll.202002303"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/smll.201703617"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2018.00006"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1309482110"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1039\/D0AN00979B"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsbiomaterials.9b01738"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/smll.202202112"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2019.119652"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsabm.1c00796"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/smll.202200757"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioactmat.2021.04.028"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2013.09.004"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/adhm.201801188"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/smll.201901269"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/natrevmats.2016.71"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/mabi.201300365"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep16691"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1089\/aivt.2020.0027"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2012-3812"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1002\/adhm.202000608"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cej.2021.132590"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2015.02.117"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2107943118"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.2000.279.5.C1295"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature14883"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.03.032"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1152\/physiol.00016.2013"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2022.992883"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biochi.2019.02.003"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41574-019-0184-8"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2022.03.002"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.biomac.0c00045"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chroma.2021.462686"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/kfz238"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-03408-4"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-06006-4"},{"key":"e_1_2_8_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.plabm.2015.11.001"},{"key":"e_1_2_8_58_1","doi-asserted-by":"publisher","DOI":"10.33176\/AACB-19-00023"},{"key":"e_1_2_8_59_1","unstructured":"OECD Test No. 236: Fish Embryo Acute Toxicity (FET) Test 2013."},{"key":"e_1_2_8_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.scitotenv.2018.03.369"},{"key":"e_1_2_8_61_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.est.8b01796"},{"key":"e_1_2_8_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/bs.ctdb.2016.10.007"},{"key":"e_1_2_8_63_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00204-020-02802-6"},{"key":"e_1_2_8_64_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.chemrestox.9b00335"},{"key":"e_1_2_8_65_1","doi-asserted-by":"publisher","DOI":"10.1002\/etc.4055"},{"key":"e_1_2_8_66_1","first-page":"1","author":"Kraft M.","year":"2022","journal-title":"Environ. Sci. Pollut. Res. Int."}],"container-title":["Small"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/smll.202300236","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/smll.202300236","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/smll.202300236","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,26]],"date-time":"2024-12-26T06:08:28Z","timestamp":1735193308000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/smll.202300236"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,18]]},"references-count":66,"journal-issue":{"issue":"25","published-print":{"date-parts":[[2023,6]]}},"alternative-id":["10.1002\/smll.202300236"],"URL":"https:\/\/doi.org\/10.1002\/smll.202300236","archive":["Portico"],"relation":{},"ISSN":["1613-6810","1613-6829"],"issn-type":[{"value":"1613-6810","type":"print"},{"value":"1613-6829","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,18]]},"assertion":[{"value":"2023-01-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-03-18","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"2300236"}}