A dual-pronged strategy for bacterial keratitis: ROS-responsive hydrogel eye drops enabling potent deep-tissue antibacterial action and NETs modulation

keratitis model, TPG@OC exhibited prolonged ocular retention, enhanced corneal penetration, and potent antibacterial efficacy, while effectively suppressing ROS accumulation, neutrophil infiltration, extracellular traps formation, and pro-inflammatory cytokine release, thereby interrupting the HMGB1-mediated inflammatory feedback loop. Notably, therapeutic evaluations in a rabbit keratitis model revealed that TPG@OC treatment extended beyond anti-infective efficacy to preserve corneal biomechanical stability, evidenced by relatively regular corneal curvature, alleviated stromal thickening, and substantially reduced deformation under intraocular pressure predicted by finite element analysis. Collectively, this work establishes a dual-pronged hydrogel platform that couples deep antimicrobial delivery with HMGB1-targeted immunoregulation to preserve corneal transparency and biomechanical integrity, offering a promising materials-based strategy for infectious keratitis therapy.