Ultrasound responsive microneedles for sequential antibacterial and immune regulation in keratitis treatment

Bacterial keratitis is a leading cause of corneal blindness, yet current antibiotic therapies suffer from poor ocular bioavailability and rising drug resistance. Effective treatment requires not only bacterial eradication but also coordinated anti-inflammation and wound repair. In this paper, we present a "two birds with one stone" strategy for bacterial keratitis treatment based on an ultrasound-activated cascade responsive core-shell microneedle. Upon corneal insertion and ultrasound stimulation, piezoelectric nanoparticles embedded in the microneedle shell generate reactive oxygen species (ROS) to eliminate bacteria. The elevated ROS levels subsequently trigger the degradation of an ROS-responsive hydrogel core, enabling sustained release of mesenchymal stem cell derived exosomes (MSC-Exos) that neutralize residual oxidative stress, promote macrophage M1 to M2 polarization, and facilitate epithelial barrier restoration. Our proposed formulation demonstrated enhanced therapeutic efficacy in a rat keratitis model, outperforming conventional antibiotic eye drops in bacterial clearance, inflammation resolution, and corneal repair. These findings establish the cascade-responsive core-shell microneedles as a clinically promising strategy for treating bacterial keratitis and other infectious ocular diseases.