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Fibrin gel as a cell carrier may provide high cell seeding efficiency and adhesion property, improved cellular interaction, and structural support to enhance cellular growth in trilayer polycaprolactone (PCL) substrates that mimic the structure of native heart valve leaflets. This cell carrier gel coupled with a trilayer PCL substrate may enable the production of native\u2010like cell\u2010cultured leaflet constructs suitable for heart valve tissue engineering. In this study, we seeded valvular interstitial cells\u00a0onto trilayer PCL substrates with fibrin gel as a cell carrier and cultured them for 1\u00a0month in vitro to determine if this gel can improve cell proliferation and production of extracellular matrix\u00a0within the trilayer cell\u2010cultured constructs. We observed that the fibrin gel enhanced cellular proliferation, their vimentin expression, and collagen and glycosaminoglycan\u00a0production, leading to improved structure and mechanical properties of the developing PCL cell\u2010cultured constructs. Fibrin gel as a cell carrier significantly improved the orientations of the cells and their produced tissue materials within trilayer PCL substrates that mimic the structure of native heart valve leaflets and, thus, may be highly beneficial for developing functional tissue\u2010engineered leaflet constructs.<\/jats:p>","DOI":"10.1002\/bit.28371","type":"journal-article","created":{"date-parts":[[2023,3,9]],"date-time":"2023-03-09T04:00:36Z","timestamp":1678334436000},"page":"1678-1693","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Fibrin gel enhanced trilayer structure in cell\u2010cultured constructs"],"prefix":"10.1002","volume":"120","author":[{"given":"Yuriy","family":"Snyder","sequence":"first","affiliation":[{"name":"Department of Bioengineering University of Missouri Columbia Missouri USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Soumen","family":"Jana","sequence":"additional","affiliation":[{"name":"Department of Bioengineering University of Missouri Columbia Missouri USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,3,18]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmbbm.2016.11.023"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.3389\/fbioe.2014.00085"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2013.06.009"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/polym13020171"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/FJC.0b013e3182116e39"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/polb.23072"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1088\/1758-5090\/ac41a1"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.3389\/fbioe.2022.920929"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2015.08.022"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2015.08.034"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2012.02.021"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.0022-202X.2004.22205.x"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s42242-020-00110-7"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2021.2133"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2012.03.015"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2016.03.007"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2011.02.018"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eurpolymj.2010.03.017"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12221-019-8795-1"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aan4587"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0142-9612(03)00051-6"},{"key":"e_1_2_9_23_1","first-page":"1","article-title":"Next\u2010generation tissue\u2010engineered heart valves with repair, remodelling and regeneration capacity","volume":"18","author":"Fioretta E. 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