{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T17:01:44Z","timestamp":1785258104407,"version":"3.55.0"},"posted":{"date-parts":[[2026,7,24]]},"group-title":"Neuroscience","reference-count":51,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T00:00:00Z","timestamp":1784851200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"name":"U.S. Army Research Office through the U.S. Department of Defense Multidisciplinary University Research Initiative (MURI) program","award":["W911NF2310276"],"award-info":[{"award-number":["W911NF2310276"]}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01NS119472 to HIC"],"award-info":[{"award-number":["R01NS119472 to HIC"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,7,24]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Rodent models are a mainstay of traumatic brain injury (TBI) research, including investigations into the pathophysiology and treatment of this condition. However, there are fundamental molecular and cellular differences between rodent and human neurons, as well as other cells of the brain. Brain organoids derived from human pluripotent stem cells recapitulate key features of the human brain and have been used to model a variety of neurological disorders. Here, we developed a novel\n                  <jats:italic>in vivo<\/jats:italic>\n                  model of human TBI based on controlled cortical impact (CCI) injuries of human organoid grafts transplanted into the brains of young adult rats. Cortical organoids derived from human induced pluripotent stem cells (iPSCs) were grown for 50-60 days\n                  <jats:italic>in vitro<\/jats:italic>\n                  before transplantation into rat visual cortex. Injures were performed 2 months later, and histological outcomes were examined at 7 or 30 days after injury. Injury cavities in the integrated grafts were identified at both endpoints with a progression toward larger cavities sizes with time. The injured human tissue exhibited evidence of neuroinflammation with elevated numbers of IBA1+ cells and axonal injury with APP+ cells. There was evidence of increased cell proliferation in the injured grafts acutely after injury that decreased with time. The injured grafts also showed evidence of phosphorylated tau aggregates and accumulation of PNAG, a polysaccharide associated with microbial pathogens. These results support the feasibility of using human organoid grafts in rats as a model of TBI, potentially including the study of long-term neurodegeneration and microbial penetration of the brain after injury.\n                <\/jats:p>","DOI":"10.64898\/2026.07.20.739683","type":"posted-content","created":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T01:25:11Z","timestamp":1784942711000},"source":"Crossref","is-referenced-by-count":0,"title":["Histological assessment of integrated human cortical organoid grafts after controlled cortical impact"],"prefix":"10.64898","author":[{"given":"Caitlyn","family":"Smith","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Hamimi","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mackenzie","family":"Castellanos","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma","family":"Noel","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA"},{"name":"Neuroscience Graduate Group, Biomedical Graduate Studies, University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Paulina","family":"Serrano","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Said","family":"Inaltekin","sequence":"additional","affiliation":[{"name":"The University of Texas at Dallas, 800 W. Campbell Road, Richardson, TX 75080-3021"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nirvaa","family":"Shah","sequence":"additional","affiliation":[{"name":"Bryn Mawr College, Department of Biology, 101 N Merion Ave, Bryn Mawr, PA 19010"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Willam","family":"Perez","sequence":"additional","affiliation":[{"name":"Vanderbilt University, 2201 West End Ave, Nashville, TN 37235"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank J.","family":"Rauscher","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaeha","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4204-6459","authenticated-orcid":false,"given":"Hailong","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria E.","family":"Johnson","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han-Chiao Isaac","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA"},{"name":"Institute of Regenerative Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA"},{"name":"Corporal Michael J. Crescenz Veterans Affairs Medical Center, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2816-0674","authenticated-orcid":false,"given":"Dennis","family":"Jgamadze","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026072809350852000_2026.07.20.739683v1.1","doi-asserted-by":"crossref","unstructured":"Faul, M. , Wald, M.M. , Xu, L. , and Coronado, V.G . (2010). Traumatic brain injury in the United States: Emergency department visits, hospitalizations, and deaths, 2002-2006. In N.C.f.I.P.a.C.U.S.D.o.I. 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