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Abstract
Severe traumatic brain injuries (sTBI) culminate in lifelong disabilities as a consequence of the significant brain tissue loss and neuronal dysfunction encountered. Clinical management of sTBI is focused heavily on rehabilitation therapy, and there are no approved treatments to help replace brain tissue and to restore lost function. Neuroprotective “bystander” immunomodulatory and neurotrophic factor signaling that is activated after sTBI is regulated by endogenous neural stem cells (NSCs). However, these effects are transient and often overwhelmed by the cytotoxic and pro-inflammatory microenvironment surrounding the lesion site. In this work, I explore the use of cell-free approaches to promote endogenous functional repair after sTBI. I hypothesized that cell-free approaches involving the use of NSC derived extracellular vesicles (EVs), and brain-mimetic chondroitin sulfate (CS) -based 3D scaffolds can be tailored to create a localized neuroprotective microenvironment that is capable of sustaining cellular and functional repair of brain tissue after sTBI. These strategies present a novel means of accelerating endogenous functional repair mechanisms and could lead to the development of clinically relevant therapeutic interventions for sTBI patients in the future.