{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T20:02:02Z","timestamp":1791316922271,"version":"4.3.1"},"reference-count":51,"publisher":"Wiley","issue":"30","license":[{"start":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T00:00:00Z","timestamp":1776988800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T00:00:00Z","timestamp":1776988800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["2T32EB005583 to HCO"],"award-info":[{"award-number":["2T32EB005583 to HCO"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["JRG L70EB033678 to JRG"],"award-info":[{"award-number":["JRG L70EB033678 to JRG"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000090","name":"Congressionally Directed Medical Research Programs","doi-asserted-by":"publisher","award":["W81XWH2010193"],"award-info":[{"award-number":["W81XWH2010193"]}],"id":[{"id":"10.13039\/100000090","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Materials"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Morphogenesis is a major developmental process that shapes organs in utero through coordinated structural deformations. Outside of simple cellular or animal models, limited models of morphogenesis exist due to the complexity of hierarchical structural change. In development, the embryonic heart undergoes a complex morphogenesis process involving looping, chamber growth, and septation, transforming the primordial tube to an adult four\u2010chambered organ. An in vitro model of looping could provide unique insights into this phase of development and improve understanding of congenital defect generation. In this study, we combined tissue engineering with developmental biology in an approach called directed morphogenesis to build a humanized tissue model of looping. To build such a model, embryonic heart tubes (EHT) mimicking native anatomy were fabricated. A perfusion bioreactor was designed to direct EHT's through a looping\u2010like process. EHTs looped in the bioreactor fused into chamber\u2010like structures with ventricular\u2010like geometry resembling early cardiac morphology. Furthermore, there was an upregulation in morphogenic genes in looped constructs after 1\u00a0week in culture, indicating biological effects from directed morphogenesis. In conclusion, a controllable in vitro model of mechanically induced cardiac morphogenetic reorganization was established, which has the potential to be translated to other organ types that undergo complex spatial reorganization.<\/jats:p>","DOI":"10.1002\/adma.202522459","type":"journal-article","created":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T11:59:21Z","timestamp":1777031961000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Engineered Development: Directed Morphogenesis of an Embryonic Heart Tube"],"prefix":"10.1002","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9229-4012","authenticated-orcid":false,"given":"Joshua R.","family":"Gershlak","sequence":"first","affiliation":[{"name":"Center for Organ Engineering Department of Surgery Massachusetts General Hospital  Boston MA USA"},{"name":"Harvard Medical School  Boston MA USA"},{"name":"John A. Paulson School of Engineering and Applied Sciences Harvard University  Cambridge MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenji","family":"Miki","sequence":"additional","affiliation":[{"name":"Center for Organ Engineering Department of Surgery Massachusetts General Hospital  Boston MA USA"},{"name":"Harvard Medical School  Boston MA USA"},{"name":"Premium Research Institute for Human Metaverse Medicine The University of Osaka  Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shoaib A.","family":"Goraya","sequence":"additional","affiliation":[{"name":"Harvard Medical School  Boston MA USA"},{"name":"Department of Cardiac Surgery Brigham and Women's Hospital  Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farhad R.","family":"Nezami","sequence":"additional","affiliation":[{"name":"Harvard Medical School  Boston MA USA"},{"name":"Department of Cardiac Surgery Brigham and Women's Hospital  Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harald C.","family":"Ott","sequence":"additional","affiliation":[{"name":"Center for Organ Engineering Department of Surgery Massachusetts General Hospital  Boston MA USA"},{"name":"Harvard Medical School  Boston MA USA"},{"name":"IVIVA Medical United Therapeutics  United Therapeutics MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,4,24]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2008.02.008"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1634\/stemcells.19\u20103\u2010193"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12015\u2010007\u20100004\u20108"},{"key":"e_1_2_10_5_1","first-page":"500","article-title":"Reconstruction and Deconstruction of Human Somitogenesis In Vitro","volume":"1","author":"Miao Y.","year":"2022","journal-title":"Nature"},{"key":"e_1_2_10_6_1","first-page":"177","article-title":"Topological Morphogenesis of Neuroepithelial Organoids","volume":"19","author":"Ishihara K.","year":"2022","journal-title":"Nature Physics"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature09941"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010020\u20102724\u20108"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1006\/dbio.2000.9753"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1203\/01.PDR.0000148710.69159.61"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/ca.20652"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibtech.2020.01.006"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.199672"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/dvdy.21483"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2023.01.001"},{"key":"e_1_2_10_16_1","first-page":"257","article-title":"Looping of Chick Embryo Hearts In Vitro","volume":"168","author":"Manning A.","year":"1990","journal-title":"Journal of Anatomy"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2014.00112"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2020.10.013"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/adhm.202001169"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1088\/1758\u20105090\/ac58be"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42003\u2010022\u201003153\u2010x"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcdd6010012"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2009.10.009"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1006\/dbio.1996.0068"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.115.306874"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2012.150"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.109.868885"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.3390\/jimaging8040095"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbm.a.35754"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1010\u20107940(00)00373\u20100"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/aja.1000300304"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2022.104600"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10439\u2010006\u20109152\u20102"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/aja.1002030105"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749\u20106632.2009.05089.x"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2004.04.033"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.152488"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1115\/1.4026645"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2022.1000684"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1123775"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1203\/00006450\u2010198802000\u201000015"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1063\/5.0172423"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1002\/1096\u20108628(200024)97:4<271::AID\u2010AJMG1277>3.0.CO;2\u2010O"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1259\/0007\u20101285\u201066\u2010783\u2010181"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2006.07.024"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.11.019"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1188302"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.2989"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1364\/AO.30.001369"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1002\/fld.5071"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brain.2024.100105"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsbiomaterials.8b01112"}],"container-title":["Advanced Materials"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/adma.202522459","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/adma.202522459","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/adma.202522459","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T15:45:00Z","timestamp":1788277500000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/adma.202522459"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,24]]},"references-count":51,"journal-issue":{"issue":"30","published-print":{"date-parts":[[2026,5]]}},"alternative-id":["10.1002\/adma.202522459"],"URL":"https:\/\/doi.org\/10.1002\/adma.202522459","archive":["Portico"],"relation":{},"ISSN":["0935-9648","1521-4095"],"issn-type":[{"value":"0935-9648","type":"print"},{"value":"1521-4095","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,24]]},"assertion":[{"value":"2025-11-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-23","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-24","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e22459"}}