Ultrasound‐Responsive Piezoelectric Fibrous Membrane Promotes Neurological Recovery After TBI by Modulating Microglial Polarization via Restoring Mitochondrial Dynamic Homeostasis

Mitochondrial dysfunction is a core pathological mechanism underlying secondary injury following traumatic brain injury, with the resulting oxidative stress and inflammatory cascade being key contributors to neurological deficits and poor clinical outcomes. This study developed an ultrasound-responsive piezoelectric fibrous membrane that, under low-intensity pulsed ultrasound (LIPUS) stimulation, generates controllable piezoelectric signals directly at the injury site to precisely regulate mitochondrial function in microglia. This regulation effectively restores mitochondrial dynamics homeostasis and enhances mitochondrial membrane potential (ΔΨm) stability, significantly suppressing the abnormal generation of mitochondrial superoxide and cellular reactive oxygen species (ROS). It promotes the polarization of microglia toward a neuroprotective M2 phenotype, reduces the expression of pro-inflammatory cytokines TNF-α, IL-1β, and IL-6, and enhances the activity of the antioxidant enzyme superoxide dismutase (SOD). In a TBI animal model, this therapeutic strategy markedly alleviated pathological brain damage, improved neuronal survival, ameliorated neurological deficits and spatial memory impairment, and facilitated the polarization of microglia toward an anti-inflammatory (M2) phenotype in the injured area. This study provides a novel strategy for TBI treatment by targeting mitochondrial function regulation, offering potential to overcome the therapeutic challenges in neuroimmunometabolic modulation.