{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T14:40:01Z","timestamp":1790347201756,"version":"4.1.0"},"reference-count":94,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"40","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2023,10,6]]},"abstract":"<jats:p>Microtia is a congenital disorder that manifests as a malformation of the external ear leading to psychosocial problems in affected children. Here, we present a tissue-engineered treatment approach based on a bioprinted autologous auricular cartilage construct (EarCartilage) combined with a bioengineered human pigmented and prevascularized dermo-epidermal skin substitute (EarSkin) tested in immunocompromised rats. We confirmed that human-engineered blood capillaries of EarSkin connected to the recipient\u2019s vasculature within 1 week, enabling rapid blood perfusion and epidermal maturation. Bioengineered EarSkin displayed a stratified epidermis containing mature keratinocytes and melanocytes. The latter resided within the basal layer of the epidermis and efficiently restored the skin color. Further, in vivo tests demonstrated favorable mechanical stability of EarCartilage along with enhanced extracellular matrix deposition. In conclusion, EarCartilage combined with EarSkin represents a novel approach for the treatment of microtia with the potential to circumvent existing limitations and improve the aesthetic outcome of microtia reconstruction.<\/jats:p>","DOI":"10.1126\/sciadv.adh1890","type":"journal-article","created":{"date-parts":[[2023,10,4]],"date-time":"2023-10-04T17:59:17Z","timestamp":1696442357000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":26,"title":["Combining bioengineered human skin with bioprinted cartilage for ear reconstruction"],"prefix":"10.1126","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7937-5216","authenticated-orcid":true,"given":"Dominika","family":"Zielinska","sequence":"first","affiliation":[{"name":"Tissue Biology Research Unit, University Children\u2019s Hospital Zurich, University of Zurich, Zurich, Switzerland."},{"name":"Children\u2019s Research Center, University Children\u2019s Hospital Zurich, Zurich, Switzerland."},{"name":"University of Zurich, Zurich, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4384-6682","authenticated-orcid":true,"given":"Philipp","family":"Fisch","sequence":"additional","affiliation":[{"name":"Tissue Engineering and Biofabrication Laboratory, Department of Health Sciences and Technology, ETH Zurich, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6418-1136","authenticated-orcid":true,"given":"Ueli","family":"Moehrlen","sequence":"additional","affiliation":[{"name":"Tissue Biology Research Unit, University Children\u2019s Hospital Zurich, University of Zurich, Zurich, Switzerland."},{"name":"Children\u2019s Research Center, University Children\u2019s Hospital Zurich, Zurich, Switzerland."},{"name":"University of Zurich, Zurich, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergio","family":"Finkielsztein","sequence":"additional","affiliation":[{"name":"Marine Polymer Technologies Inc., Tewksbury, MA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5187-3010","authenticated-orcid":true,"given":"Thomas","family":"Linder","sequence":"additional","affiliation":[{"name":"Klinik f\u00fcr Hals-, Nasen-, Ohren- und Gesichtschirurgie, Luzerner Kantonsspital, Luzern, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8522-9909","authenticated-orcid":true,"given":"Marcy","family":"Zenobi-Wong","sequence":"additional","affiliation":[{"name":"Tissue Engineering and Biofabrication Laboratory, Department of Health Sciences and Technology, ETH Zurich, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Biedermann","sequence":"additional","affiliation":[{"name":"Tissue Biology Research Unit, University Children\u2019s Hospital Zurich, University of Zurich, Zurich, Switzerland."},{"name":"Children\u2019s Research Center, University Children\u2019s Hospital Zurich, Zurich, Switzerland."},{"name":"University of Zurich, Zurich, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3521-8010","authenticated-orcid":true,"given":"Agnes S.","family":"Klar","sequence":"additional","affiliation":[{"name":"Tissue Biology Research Unit, University Children\u2019s Hospital Zurich, University of Zurich, Zurich, Switzerland."},{"name":"Children\u2019s Research Center, University Children\u2019s Hospital Zurich, Zurich, Switzerland."},{"name":"University of Zurich, Zurich, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"crossref","unstructured":"J. Avelar Ear Reconstruction (Springer-Verlag Berlin Heidelberg 2013).","DOI":"10.1007\/978-3-642-35683-4"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.32.6.453"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.sap.0000155284.96308.32"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bjps.2009.09.005"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.fsc.2017.09.006"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1097\/SCS.0000000000003751"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.fsc.2016.06.011"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00266-012-0008-x"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1097\/00006534-199308000-00001"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12663-018-1158-4"},{"key":"e_1_3_2_12_2","doi-asserted-by":"crossref","unstructured":"J. F. Reinisch Evolution of porous polyethylene ear reconstruction in Modern Microtia Reconstruction: Art Science and New Clinical Techniques J. F. Reinisch Y. Tahiri Eds. (Springer International Publishing 2019) pp. 321\u2013334.","DOI":"10.1007\/978-3-030-16387-7_19"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.fsc.2017.09.009"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamafacial.2014.30"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1097\/GOX.0b013e3182aa8784"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijporl.2018.09.035"},{"key":"e_1_3_2_17_2","doi-asserted-by":"crossref","unstructured":"J. F. Reinisch Y. Tahiri Polyethylene ear reconstruction: A state-of-the-art surgical technique in Modern Microtia Reconstruction: Art Science and New Clinical Techniques J. F. Reinisch Y. Tahiri Eds. (Springer International Publishing 2019) pp. 91\u2013110.","DOI":"10.1007\/978-3-030-16387-7_6"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.otot.2017.03.002"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bjps.2014.07.024"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bjps.2007.07.012"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijporl.2008.05.006"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0253149"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0202356"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.apmt.2020.100724"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1002\/term.2613"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1097\/00006534-199708000-00001"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0234650"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1002\/term.3332"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1177\/1947603514546740"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1177\/19476035211049556"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1002\/adfm.202008261"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1097\/PRS.0000000000005746"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1097\/BCR.0000000000000401"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1989.03430150093032"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.burnso.2021.02.002"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellbi.2007.03.009"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1111\/pcmr.12609"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-6143.2005.00790.x"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00383-013-3451-0"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1089\/ten.tec.2011.0561"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1177\/20417314221088513"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cobme.2019.09.013"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-21005-9"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1097\/GOX.0000000000001610"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbiomech.2015.12.032"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1115\/1.4042201"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2008.254"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1089\/ten.tea.2011.0543"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1002\/jbm.b.33639"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0142-9612(03)00501-5"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1089\/ten.tea.2015.0173"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1097\/PRS.0b013e31824a2c1c"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.1097\/00005537-200405000-00015"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.1088\/1758-5082\/6\/2\/024103"},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202001419"},{"key":"e_1_3_2_56_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41578-020-0213-1"},{"key":"e_1_3_2_57_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2022.02.037"},{"key":"e_1_3_2_58_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41536-020-00099-8"},{"key":"e_1_3_2_59_2","doi-asserted-by":"publisher","DOI":"10.1002\/jor.21503"},{"key":"e_1_3_2_60_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2014.04.107"},{"key":"e_1_3_2_61_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-40575-w"},{"key":"e_1_3_2_62_2","doi-asserted-by":"publisher","DOI":"10.1006\/excr.1999.4708"},{"key":"e_1_3_2_63_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmat4993"},{"key":"e_1_3_2_64_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbiomech.2014.10.017"},{"key":"e_1_3_2_65_2","doi-asserted-by":"publisher","DOI":"10.1089\/ten.tea.2016.0467"},{"key":"e_1_3_2_66_2","doi-asserted-by":"publisher","DOI":"10.1097\/PRS.0000000000006906"},{"key":"e_1_3_2_67_2","doi-asserted-by":"publisher","DOI":"10.1089\/ten.tea.2010.0125"},{"key":"e_1_3_2_68_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00383-016-4031-x"},{"key":"e_1_3_2_69_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00383-012-3217-0"},{"key":"e_1_3_2_70_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mrfmmm.2004.11.016"},{"key":"e_1_3_2_71_2","doi-asserted-by":"publisher","DOI":"10.1089\/ten.tea.2014.0327"},{"key":"e_1_3_2_72_2","doi-asserted-by":"publisher","DOI":"10.1096\/fj.06-6649rev"},{"key":"e_1_3_2_73_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3006894"},{"key":"e_1_3_2_74_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.R700026200"},{"key":"e_1_3_2_75_2","doi-asserted-by":"publisher","DOI":"10.1177\/20417314211028574"},{"key":"e_1_3_2_76_2","doi-asserted-by":"publisher","DOI":"10.1088\/1758-5090\/8\/3\/032001"},{"key":"e_1_3_2_77_2","doi-asserted-by":"publisher","DOI":"10.1089\/ten.tea.2019.0201"},{"key":"e_1_3_2_78_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.burns.2011.01.022"},{"key":"e_1_3_2_79_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.burns.2016.06.013"},{"key":"e_1_3_2_80_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-09709-6"},{"key":"e_1_3_2_81_2","doi-asserted-by":"publisher","DOI":"10.1089\/wound.2012.0393"},{"key":"e_1_3_2_82_2","doi-asserted-by":"publisher","DOI":"10.1186\/rr72"},{"key":"e_1_3_2_83_2","doi-asserted-by":"publisher","DOI":"10.1093\/rb\/rbac102"},{"key":"e_1_3_2_84_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mtbio.2021.100098"},{"key":"e_1_3_2_85_2","doi-asserted-by":"publisher","DOI":"10.1111\/joa.12840"},{"key":"e_1_3_2_86_2","doi-asserted-by":"crossref","unstructured":"A. M. Wes J. A. Taylor Anatomy and anthropometry of the ear in Modern Microtia Reconstruction: Art Science and New Clinical Techniques J. F. Reinisch Y. Tahiri Eds. (Springer International Publishing 2019) pp. 1\u201311.","DOI":"10.1007\/978-3-030-16387-7_1"},{"key":"e_1_3_2_87_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00405-013-2797-1"},{"key":"e_1_3_2_88_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bjps.2008.07.008"},{"key":"e_1_3_2_89_2","first-page":"406","article-title":"The use of a fascial flap in ear reconstruction","volume":"60","author":"Tegtmeier R. E.","year":"1977","unstructured":"R. E. Tegtmeier, R. A. Gooding, The use of a fascial flap in ear reconstruction. Plast. Reconstr. Surg. 60, 406\u2013411 (1977).","journal-title":"Plast. Reconstr. Surg."},{"key":"e_1_3_2_90_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2014.02.049"},{"key":"e_1_3_2_91_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00383-015-3808-7"},{"key":"e_1_3_2_92_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-0029-1239448"},{"key":"e_1_3_2_93_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00383-010-2777-0"},{"key":"e_1_3_2_94_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00383-010-2792-1"},{"key":"e_1_3_2_95_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00383-011-2990-5"}],"container-title":["Science Advances"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/sciadv.adh1890","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,9]],"date-time":"2024-01-09T21:25:42Z","timestamp":1704835542000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/sciadv.adh1890"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,10,6]]},"references-count":94,"journal-issue":{"issue":"40","published-print":{"date-parts":[[2023,10,6]]}},"alternative-id":["10.1126\/sciadv.adh1890"],"URL":"https:\/\/doi.org\/10.1126\/sciadv.adh1890","relation":{},"ISSN":["2375-2548"],"issn-type":[{"value":"2375-2548","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,10,6]]},"assertion":[{"value":"2023-02-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-09-01","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-10-04","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"eadh1890"}}