Ultrasound Activated Piezoelectric Dural Patches to Drive Endogenous Neural Stem Cell-Mediated Repair Traumatic Brain Injury.

Abstract

Endogenous neuronal differentiation of neural stem cells (NSCs) is a promising route to restore function after traumatic brain injury (TBI), but direct transplantation of exogenous NSCs faces practical and immunological barriers and yields limited neuronal maturation. Here, a clinically relevant strategy is reported that converts a dura mater into an active piezoelectric patch to noninvasively drive endogenous NSC neurogenesis. Electrospun poly(L‑lactic acid) (PLLA) patches were subjected to surface confinement crystallization on metal substrates, producing a metastable α' crystal structure and markedly enhanced piezoelectric output. Under low‑intensity transcranial ultrasound, the treated patch generates reproducible pulsed electrical signals that remodel the local injury microenvironment. In vitro and in vivo assays show that ultrasound‑activated patches increase neuronal lineage differentiation (neurons/astrocytes ratio increased ∼9.6‑fold at 14 days) and promote greater neuronal maturation, while concomitantly modulating the immune milieu. In a rat TBI model, daily 2‑min ultrasound stimulation delivered via the patch substantially accelerated tissue repair and improved behavioral and cognitive outcomes compared with untreated controls. This work demonstrates a simple, scalable modification of clinical artificial dura mater to produce a soft, biodegradable piezoelectric implant capable of remote, noninvasive electrical modulation of endogenous NSCs, with broad implications for neural regeneration and potential clinical translation.