EP-273 Magnetic nanoparticle administration to a model of penetrating neurotrauma in vitro

Abstract

Abstract Introduction/Aims Functional recovery in penetrating traumatic brain injury (pTBI) is hampered due to the lack of clinically approved regenerative therapies. Although a surgical emergency, pTBI management is largely supportive, with no targeted neuroregenerative therapies. Reactive gliotic and neuroinflammatory responses with a lack of spontaneous axonal regeneration represent a major barrier to repair. Emergent nanotechnologies including magnetic nanoparticles (MNPs) show promise to attenuate such responses through immunomodulation, with potential of delivery of neurotherapeutic molecules to lesion sites during surgical intervention. However, there is a lack of high throughput, neuropathomimetic, models for nano/biomaterial testing in experimental neurology. Our group recently showed glial cell interactions with a surgical biomaterial scaffold (DuraGen PlusTM) in a novel in vitro model of pTBI. Methods Mice cerebral cortices were extracted and cultured 8–10 days in vitro (DIV) using previous methodology (Basit et al, Mat Sci Eng C, 2021) with a modified chemical medium. At 8 DIV, a sterile pipette was used for transection of the culture simulating penetrating injury in vitro with injection of carboxymethyl dextran-coated magnetic nanoparticles and polyethylene glycol-coated magnetic nanoparticles into the lesion site. MNP-neural cell responses were evaluated using immunocytochemistry methods. Results Our model demonstrates hallmark reactive gliotic responses, immune cell infiltration and axonal transection in injury sites. We demonstrate preferential and competitive microglial uptake of delivered MNPs versus other neural cell types (p<0.05, n=5). Conclusion The model is adaptable to study neural cell responses to range of materials, offering high versatility for testing promising surgical neuromaterial based therapeutic interventions in experimental clinically relevant research.