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Specifically, we employ a bioengineered 3D brain\u2010like human tissue culture system composed of collagen\u2010infused silk protein donut\u2010like hydrogels embedded with human IPSC\u2010derived neurons, human astrocytes, and a human microglial cell line. We have utilized this system within an advanced blast simulator (ABS) to expose the 3D brain cultures to a blast wave that can be precisely controlled. These 3D cultures are enclosed in a 3D\u2010printed surrogate skull\u2010like material containing media which are then placed in a holder apparatus inside the ABS. This allows for exposure to the blast wave alone without any secondary injury occurring. We show that blast induces an increase in lactate dehydrogenase activity and glutamate release from the cultures, indicating cellular injury. Additionally, we observe a significant increase in axonal varicosities after blast. These varicosities can be stained with antibodies recognizing amyloid precursor protein. The presence of amyloid precursor protein deposits may indicate a blast\u2010induced axonal transport deficit. After blast injury, we find a transient release of the known TBI biomarkers, UCHL1 and NF\u2010H at 6\u2009h and a delayed increase in S100B at 24 and 48\u2009h. This in vitro model will enable us to gain a better understanding of clinically relevant pathological changes that occur following primary blast and can also be utilized for discovery and characterization of biomarkers.<\/jats:p>","DOI":"10.1002\/jnr.25123","type":"journal-article","created":{"date-parts":[[2022,10,6]],"date-time":"2022-10-06T05:47:17Z","timestamp":1665035237000},"page":"3-19","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Development of a novel bioengineered 3D brain\u2010like tissue for studying primary blast\u2010induced traumatic brain injury"],"prefix":"10.1002","volume":"101","author":[{"given":"Dustin M.","family":"Snapper","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Molecular Therapeutics Uniformed Services University  Bethesda Maryland 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