Innovative and Adaptive Drug Delivery System for Enhanced Neuroprotection and Repair in Traumatic Brain Injuries from Penetrating Trauma or Open Skull Fractures in Low Resource Environments

Penetrating Traumatic Brain Injuries (TBI) pose critical emergency situations with high mortality risks in both civilian and military settings, especially in remote or conflict zones where immediate surgical interventions may not be feasible. The onset of neurodegeneration in such cases can lead to catastrophic secondary injuries. This research aims to explore the potential application of a novel wound dressing/drug delivery system as a neuroprotective therapy. This system would cover and safeguard exposed brain tissue while actively delivering pharmaceutical agents to enhance survivability and long-term outcomes. The proposed project leverages a commercially available hydrogel-based wound dressing with a proven safety record in treating complex wounds and stabilizing severe trauma in resource-limited environments pending surgical intervention. This biocompatible material forms a long-lasting, oxygen-permeable, and moist matrix, preventing bacterial penetration while facilitating exudate flow through vapor transpiration. Additionally, it has demonstrated sustained release capabilities for various chemical and biological agents in large animal studies. This proposal aims to test the wound matrix in combination with therapeutic agents known to improve TBI outcomes by evaluating their safety and efficacy using rodent models. The goal is to develop a kit where a pro-healing hydrogel wound matrix can be combined with anti-inflammatory, hemostatic, and infection management agents tailored to address TBI-induced brain swelling, raw surface bleeding, and infection risks. Each active agent, in both liquid and solid forms, will undergo testing. The research will focus on incorporating each of the hemostatic, anti-inflammatory and infection management agents into the wound matrix to form a suitable cover for open brain tissue. The protoypes will then be applied to rodents subjected to the the cortical collision impact model to determine their effects post-TBI on edema, inflammatory mediators and histology/immunohistochemistry in the brain.  A prototype combining an anti-inflammatory and infection management agent will also undergo evaluation to offer a multifaceted solution. The findings will provide data to select the optimal prototypes for early discussions with the FDA in order to identify pre-clinical and clinical studies that will be necessary to advance regulatory approvals and further their development to enable better management of penetrating TBIs in diverse settings.