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We established a biomaterial-based CAVD model mimicking the biomechanics of the human AV disease-prone fibrosa layer, three-dimensional (3D)\u2013bioprinted into 96-well arrays. Liquid chromatography\u2013tandem mass spectrometry analyses probed the cellular proteome and vesiculome to compare the 3D-bioprinted model versus traditional 2D monoculture, against human CAVD tissue. The 3D-bioprinted model highly recapitulated the CAVD cellular proteome (94% versus 70% of 2D proteins). Integration of cellular and vesicular datasets identified known and unknown proteins ubiquitous to AV calcification. This study explores how 2D versus 3D-bioengineered systems recapitulate unique aspects of human disease, positions multiomics as a technique for the evaluation of high throughput\u2013based bioengineered model systems, and potentiates future drug discovery.<\/jats:p>","DOI":"10.1126\/sciadv.adj9793","type":"journal-article","created":{"date-parts":[[2024,2,28]],"date-time":"2024-02-28T13:59:54Z","timestamp":1709128794000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":33,"title":["Intracellular proteomics and extracellular vesiculomics as a metric of disease recapitulation in 3D-bioprinted aortic valve arrays"],"prefix":"10.1126","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2441-4251","authenticated-orcid":true,"given":"Cassandra L.","family":"Clift","sequence":"first","affiliation":[{"name":"Division of Cardiovascular Medicine, Department of Medicine, Center for Interdisciplinary Cardiovascular Sciences, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA 02115, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3923-9786","authenticated-orcid":true,"given":"Mark C.","family":"Blaser","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Department of Medicine, Center for Interdisciplinary Cardiovascular Sciences, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA 02115, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Willem","family":"Gerrits","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Department of Medicine, Center for Interdisciplinary Cardiovascular Sciences, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA 02115, USA."},{"name":"Department of Cardiothoracic Surgery, University Medical Center Utrecht, Utrecht, Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6431-5077","authenticated-orcid":true,"given":"Mandy E.","family":"Turner","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Department of Medicine, Center for Interdisciplinary Cardiovascular Sciences, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA 02115, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1166-6479","authenticated-orcid":true,"given":"Abhijeet","family":"Sonawane","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Department of Medicine, Center for Interdisciplinary Cardiovascular Sciences, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA 02115, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tan","family":"Pham","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Department of Medicine, Center for Interdisciplinary Cardiovascular Sciences, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA 02115, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason L.","family":"Andresen","sequence":"additional","affiliation":[{"name":"Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA."},{"name":"Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5585-9280","authenticated-orcid":true,"given":"Owen S.","family":"Fenton","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139, USA."},{"name":"Division of Pharmacoengineering and Molecular Pharmaceutics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5418-7235","authenticated-orcid":true,"given":"Joshua M.","family":"Grolman","sequence":"additional","affiliation":[{"name":"John A. 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