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 outlines laboratory testing to combine therapeutic agents known to improve TBI outcomes with the wound matrix, evaluating their controlled release profiles and identifying optimal dosages. 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. Three dosages of each active agent, in both liquid and solid forms, will undergo testing to mimic therapeutic approximations. The research will focus on incorporating these agents into the wound matrix to form a suitable cover for open brain tissue, assessed through various physical tests. Analytical methods will determine drug loading during dressing formation, while flow cells will study the release kinetics of each therapeutic agent over time, elucidating their release profiles with different loading techniques. A prototype combining an anti-inflammatory and antibiotic will also undergo evaluation to offer a multifaceted solution. The findings will inform further in vivo studies using TBI models, driving the development of effective neuroprotective strategies for managing penetrating TBIs in diverse settings.