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Human relevant models are thus urgently required. Here, an in vitro mild TBI (mTBI) modeling system is reported based on 3D cultured human induced pluripotent stem cells (iPSC) derived neural progenitor cells (iPSC\u2010NPCs) to evaluate consequences of single and repetitive mTBI using a 3D printed mini weight\u2010drop impact device. Computational simulation is performed to understand the single\/cumulative effects of weight\u2010drop impact on the NPC differentiated neurospheres. Experimental results reveal that neurospheres show reactive astrogliosis and glial scar formation after repetitive (10 hits) mild impacts, while no astrocyte activation is found after one or two mild impacts. A 3D co\u2010culture model of human microglia cells with neurospheres is further developed. It is found that astrocyte response is promoted even after two mild impacts, possibly caused by the chronic neuroinflammation after microglia activation. The in vitro mTBI modeling system recapitulates several hallmarks of the brain impact injury and might serve as a good platform for future drug screening.<\/jats:p>","DOI":"10.1002\/adhm.202100180","type":"journal-article","created":{"date-parts":[[2021,4,23]],"date-time":"2021-04-23T03:29:49Z","timestamp":1619148589000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Design and Evaluation of an In Vitro Mild Traumatic Brain Injury Modeling System Using 3D Printed Mini Impact Device on the 3D Cultured Human iPSC Derived Neural Progenitor Cells"],"prefix":"10.1002","volume":"10","author":[{"given":"Wen","family":"Shi","sequence":"first","affiliation":[{"name":"Mary &amp; Dick Holland Regenerative Medicine Program University of Nebraska  Medical Center Omaha NE 68198 USA"},{"name":"Division of Cardiology Department of Internal Medicine University of Nebraska  Medical Center Omaha NE 68198 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pengfei","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Chemical Engineering and Science Florida Institute of Technology  Melbourne FL 32901 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitchell A.","family":"Kuss","sequence":"additional","affiliation":[{"name":"Mary &amp; Dick Holland Regenerative Medicine Program University of Nebraska  Medical Center Omaha NE 68198 USA"},{"name":"Division of Cardiology Department of Internal Medicine University of Nebraska  Medical Center Omaha NE 68198 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linxia","family":"Gu","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Chemical Engineering and Science Florida Institute of Technology  Melbourne FL 32901 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Forrest","family":"Kievit","sequence":"additional","affiliation":[{"name":"Department of Biological Systems Engineering University of Nebraska\u2010Lincoln  Lincoln NE 68583 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyung Joon","family":"Kim","sequence":"additional","affiliation":[{"name":"Mary &amp; Dick Holland Regenerative Medicine Program University of Nebraska  Medical Center Omaha NE 68198 USA"},{"name":"Eppley Institute University of Nebraska Medical Center  Omaha NE 68198 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5647-3793","authenticated-orcid":false,"given":"Bin","family":"Duan","sequence":"additional","affiliation":[{"name":"Mary &amp; Dick Holland Regenerative Medicine Program University of Nebraska  Medical Center Omaha NE 68198 USA"},{"name":"Division of Cardiology Department of Internal Medicine University of Nebraska  Medical Center Omaha NE 68198 USA"},{"name":"Department of Surgery University of Nebraska Medical Center  Omaha NE 68198 USA"},{"name":"Department of Mechanical Engineering University of Nebraska\u2010Lincoln  Lincoln NE 68588 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,4,23]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.1097\/00001199-200609000-00001"},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.4103\/1673-5374.257520"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pmr.2011.08.009"},{"key":"e_1_2_9_4_1","first-page":"623","volume":"89","author":"Mayer A. 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