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Penetrating traumatic brain injury (pTBI) management is largely supportive, with no clinically established regenerative therapies. Neurocompatible biomaterials offer a high potential to promote regenerative mechanisms but facile, high throughput, pathomimetic in vitro pTBI models for the developmental testing of neuro-materials is lacking. Method A mouse mixed glial culture system was utilised within which penetrating injuries could be induced. DuraGen PlusTM – an FDA approved neurosurgical grade biomaterial could be implanted into lesions to assess cell-biomaterial responses. Reactive gliosis (astrocytic morphological responses/GFAP expression) and microglial infiltration (Iba1 expression) were assessed/quantified. Results Key pathological features of pTBI were observed in the model, with the ability to (i) introduce reproducible lesions (diameter 949 ± 26 μm) and (ii) for DuraGen PlusTM to be implanted into lesions. Peri-lesional astrocytes displayed hypertrophic palisading morphologies and GFAP upregulation, analogous to gliosis in vivo. Significant microglial numbers infiltrated the DuraGen PlusTM implant at 7 days post-lesion (132.41 ± 15.83 cells/mm2) versus lesion only (82.04 ± 5.11 cells/mm2), p &amp;lt; 0.05). Conclusions We have developed a novel, neuropathomimetic pTBI model, wherein biomaterial implantation enables investigation of neural cell-biomaterial responses. This model can facilitate early-stage evaluation of novel biomaterials as high throughput, inexpensive and facile screening tool.

518 New In Vitro Model of Traumatic Brain Injury to Assess Biomaterial Based Regenerative Strategies