The effect of an ultrasound-activated electrospun piezoelectric hydrogel scaffold on post-traumatic brain injury motor function in Drosophila melanogaster

Traumatic brain injury (TBI) is a leading cause of long-term neurological disability, affecting 50-60 million people annually. Cascading secondary injury mechanisms, including oxidative stress and neuroinflammation, impair motor and cognitive function, while current therapies often manage symptoms rather than restore lost neurological function. This study investigated an ultrasound-activated piezoelectric hydrogel scaffold composed of barium titanate nanoparticles (BTNPs), sodium alginate (SA), and polyethylene oxide (PEO). The hypothesis was that TBI flies receiving the scaffold and ultrasound would display a higher climbing assay pass rate than TBI flies receiving no treatment or BTNPs alone. TBI was induced in Drosophila melanogaster with a high-impact trauma (HIT) apparatus. Treatments were applied by opening and resealing the fly head cuticle, followed by ultrasound stimulation. Motor recovery was quantified with a climbing assay across four groups (N=10 flies per group), which measured the percentage of flies that could cross a 5 cm mark within 30 seconds. Assay validity was supported by a statistically significant difference between flies without TBI and those with TBI using Mann-Whitney U testing (p=0.0035). Although TBI treatment groups did not differ significantly (p>0.05), median pass rates increased from injury control (35%) to BTNPs (45%) to scaffold (50%). However, high inter-trial variation, a 45.2% procedural mortality rate, and small sample size limited statistical power. These results suggest that piezoelectric electrospun hydrogel scaffolds may be a pathway for safer and more biocompatible restoration after TBI, but provide insufficient evidence to conclude that the scaffold significantly improved motor recovery.