Pilot Rodent Study Utilizing Targeted Dexamethasone Polymeric Fibers in Place of Two-Stage Decompressive Craniectomy and Cranioplasty

Abstract

Background: Traumatic brain injury (TBI) poses significant challenges due to its complex pathology with cerebral edema being a critical complication. Moderate-to-severe TBI is most often managed with a surgical intervention utilizing a two-stage decompressive craniectomy (DC) and cranioplasty. This study investigates a novel, minimally invasive approach using biodegradable polymer fibers for targeted, sustained dexamethasone (DEX) delivery as a minimally invasive surgical alternative. Method: Adult male Long Evans rats (n = 12) were used to assess the efficacy of intraparenchymal sustained-release DEX fibers for moderate-to-severe focal TBI. Rats were randomized to receive DEX fibers at the injury site or a single intramuscular DEX dose. Functional recovery was evaluated via skilled reaching tasks, and systemic DEX levels were monitored using venous sampling and high-performance liquid chromatography. Statistical analysis confirmed the potential of targeted DEX delivery for enhancing TBI recovery (P < .05). Results: Motor recovery following TBI was evaluated using the skilled reaching task, with Group #1 (targeted DEX fiber placement) showing significantly higher post-TBI recovery scores compared to Group #2 (systemic intramuscular DEX) at all timepoints (P < .0001). Longitudinal analysis confirmed sustained DEX release in Group #1 with minimal systemic absorption, whereas Group #2 exhibited negligible systemic DEX levels beyond 48 hours. These results demonstrate the efficacy of targeted DEX delivery in enhancing neurobehavioral recovery while minimizing systemic exposure, addressing limitations of conventional systemic therapies in TBI management. Conclusion: TBI remains a major global health challenge with limited treatment options and significant morbidity and mortality. This study demonstrates that intraparenchymal sustained-release DEX fibers improve motor recovery and mitigate systemic side effects compared to systemic corticosteroid use. These findings highlight the potential for targeted, localized DEX therapy as a minimally invasive alternative to DC and cranioplasty.