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Here, we report a five\u2010cell\u2010type human neurovascular culture system, comprising endothelial cells, astrocytes, pericytes, microglia, and neurons, engineered within a 3D scaffold to study injury\u2010induced remodeling over multiple weeks. This PENTA\u2010culture platform captures key structural and molecular features of the neurovascular unit and supports compartment\u2010resolved profiling of vascular and neuroimmune responses. Under baseline conditions, PENTA cultures exhibit restricted tracer distribution relative to simpler culture configurations, consistent with the emergence of barrier\u2010like properties within the 3D scaffold. Following mechanical trauma, cultures exhibit a biphasic response characterized by acute endothelial disorganization, mitochondrial structural changes, and neuroimmune alterations, followed by delayed and incomplete structural recovery, accompanied by shifts in angiogenic and immunomodulatory signaling consistent with Tyrosine kinase with immunoglobulin\u2010like epidermal growth factor\u2010like domains 2\u00a0(Tie2)\u2010 and Janus kinase\/Signal Transducer and Activator of Transcription (JAK\/STAT)\u2010associated signatures. At last, the inclusion of microglia and neurons is associated with improved cytokine resolution and partial recovery of junctional organization, highlighting the influence of neuroimmune complexity on post\u2010injury vascular remodeling. Together, this long\u2010lived, human\u2010derived platform provides a structurally complex and functionally informative system for characterizing neurovascular injury signatures following TBI.<\/jats:p>","DOI":"10.1002\/adhm.202504884","type":"journal-article","created":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T08:02:27Z","timestamp":1777449747000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A Long\u2010Lived Human Neurovascular PENTA Culture Model Captures Incomplete Vascular Repair and Glia\u2010Associated Signaling After Traumatic Brain Injury"],"prefix":"10.1002","volume":"15","author":[{"given":"Daniel S.","family":"Hinrichsen","sequence":"first","affiliation":[{"name":"Biomedical Engineering Department University of Cincinnati  Cincinnati USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-4722-0884","authenticated-orcid":false,"given":"Sunghyun","family":"Jun","sequence":"additional","affiliation":[{"name":"Biomedical Engineering Department University of Cincinnati  Cincinnati USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colleen M.","family":"Arrasmith","sequence":"additional","affiliation":[{"name":"Biomedical Engineering Department University of Cincinnati  Cincinnati USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charitha C.","family":"Anamala","sequence":"additional","affiliation":[{"name":"Biomedical Engineering Department University of Cincinnati  Cincinnati USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitchell D.","family":"Thielen","sequence":"additional","affiliation":[{"name":"Biomedical Engineering Department University of Cincinnati  Cincinnati USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anapaula","family":"Garcia","sequence":"additional","affiliation":[{"name":"Biomedical Engineering Department University of Cincinnati  Cincinnati USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9409-0136","authenticated-orcid":false,"given":"Volha","family":"Liaudanskaya","sequence":"additional","affiliation":[{"name":"Biomedical Engineering Department University of Cincinnati  Cincinnati USA"},{"name":"Neuroscience Graduate Program College of Medicine University of Cincinnati  Cincinnati Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,4,29]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2021.05.025"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.3233\/rnn\u2010130354"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2017.07.010"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2013.00018"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.5414\/NP301130"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10571\u2010023\u201001372\u20102"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40478\u2010021\u201001178\u20107"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcn.2015.03.001"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1089\/neu.2023.0102"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2203199"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2021.818169"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1080\/87565641.2014.973959"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1177\/0271678X17701460"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/burnst\/tkad033"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2018.01.021"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2012.02.013"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature09613"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2019.06.002"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awx350"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419\u2010021\u201004333\u2010z"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/adfm.201909146"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1089\/neu.2018.5990"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.24271"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbm.a.37816"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0128890"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xpro.2021.100563"},{"key":"e_1_2_12_28_1","doi-asserted-by":"crossref","unstructured":"A. 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