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In this study, we engineered large-diameter fibrin-based vascular grafts with a target inner diameter of 21\u00a0mm replicating all three layers of the native human vessel wall in vitro.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      The\n                      <jats:italic>Tunica media<\/jats:italic>\n                      was reconstructed using a compressed high-density (25\u00a0mg\/mL) fibrin matrix seeded with smooth muscle cells expressing \u03b1-SMA and calponin, differentiated from adipose-derived mesenchymal stem cells (ASCs). The\n                      <jats:italic>Adventitia<\/jats:italic>\n                      -equivalent was formed in a 5\u00a0mg\/mL fibrin gel containing ASCs, human umbilical vein endothelial cells (HUVECs), and normal human dermal fibroblasts (NHDFs) to enable the formation of a capillary-like network resembling the native adventitial\n                      <jats:italic>Vasa vasorum<\/jats:italic>\n                      . The luminal surface was endothelialized with HUVECs to replicate the\n                      <jats:italic>Tunica intima<\/jats:italic>\n                      . While controls were cultured statically for 7\u00a0days, other grafts were evaluated under pulsatile perfusion at physiological pressures using the TransMedics\n                      <jats:sup>\u00ae<\/jats:sup>\n                      \u201cOrgan Care System Heart\n                      <jats:sup>\u2122<\/jats:sup>\n                      \u201d.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The stepwise fabrication technique resulted in three-layered bioartificial vessel equivalents with a mean inner diameter of 21\u00a0mm. All constructed vessels (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20093) maintained sufficient biomechanical stability to withstand physiological pressure (120.9\u2009\u00b1\u20091.2 to 61.4\u2009\u00b1\u200912.5\u00a0mmHg) at 60\u00a0bpm throughout the perfusion period. The aortic grafts exhibited a cyclic stretch (8.95\u2009\u00b1\u20092.03%) within the physiological range of native vessels. Mechanical stimulation induced a layer-specific physiological cell morphology and alignment across all three layers of the vascular wall. Endothelial coverage was high on static grafts (81.39\u2009\u00b1\u20092.37%) and on one of three dynamic grafts. Shear stress during perfusion (0.38\u2009\u00b1\u20090.03 dyn cm\n                      <jats:sup>\u22122<\/jats:sup>\n                      ) remained below physiological levels, and further evaluation under prolonged perfusion (&gt; 21\u00a0days) is required to assess long-term biomechanical stability and vascular functionality.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This approach may be considered a proof of concept and constitutes a first step toward the development of biometric and functional large-diameter vessel replacements.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s10439-026-04087-9","type":"journal-article","created":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T14:05:00Z","timestamp":1774620300000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Generation of Fibrin-Based Aortic Vessels with Layer-Specific Cell Architecture Under Pulsatile Perfusion in a Clinical Organ Care System"],"prefix":"10.1007","author":[{"given":"Celina Delia","family":"K\u00e4ding","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clara-Sophie","family":"Glomb","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Stadler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Imke","family":"Becker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie","family":"Klingenberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans-Klaus","family":"H\u00f6ffler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Pflaum","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arjang","family":"Ruhparwar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathias","family":"Wilhelmi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5788-974X","authenticated-orcid":false,"given":"Florian","family":"Helms","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,3,27]]},"reference":[{"key":"4087_CR1","doi-asserted-by":"publisher","first-page":"2100","DOI":"10.1016\/S0140-6736(24)00367-2","volume":"403","author":"GBD 2021 Causes of Death Collaborators","year":"2024","unstructured":"GBD 2021 Causes of Death Collaborators. 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