A Bioadhesive Wireless Bioelectric Interface for Single-Dose Prevention of Acute Lung Injury via Piezoelectric Immunomodulation.

Effective management of acute lung injury (ALI) necessitates both prolonged pulmonary retention and precise immune modulation. Here, we report a novel bioadhesive piezoelectric immunomodulator (PNS@PDA), designed to establish a persistent and wireless bioelectric interface for on-demand immunomodulation within the pulmonary microenvironment. Utilizing a mussel-inspired polydopamine (PDA) shell, PNS@PDA exhibits robust tethering to lung parenchyma, achieving a 6.3-fold higher lung accumulation than bare piezoelectric bismuth oxychloride nanosheets (PNS) 32 h postinhalation. Meanwhile, low-intensity ultrasound (1.0 W/cm2) generates on-demand bioelectric cues (>150 mV) that reprogram macrophages from a pro-inflammatory M1 to an anti-inflammatory M2 phenotype by suppressing oxidative stress and NF-κB signaling. In a murine ALI model, a single intranasal dose of PNS@PDA provides potent preventive protection, effectively quenching cytokine storms and restoring alveolar integrity. This work introduces an innovative, on-demand, and wireless biophysical strategy for ALI intervention, offering a generalizable paradigm for the nonpharmacological treatment of acute inflammatory disorders.