Enzyme-Mimetic Hydrogel Balancing Antibacterial Activity and Cytoprotection for Corneal Regeneration in Bacterial Keratitis.

Abstract

Current bacterial keratitis treatments, ranging from topical antibiotics to sutured corneal grafts, fail to concurrently address infection control, inflammation modulation, and tissue regeneration. To reconcile effective antimicrobial action with host-tissue protection, we developed an injectable bioinspired composite matrix that integrated photoresponsive collagen/hyaluronic acid-nitrobenzene conjugate (CHB) hydrogel with multifunctional carbon dots (CDs) derived from curcumin and chitosan (CC-CDs). Upon injection, the CHB hydrogel forms a transparent adhesive interface in situ, while the CC-CDs leverage cationic chitosan for targeted bacterial membrane disruption and curcumin-derived nanoenzyme activity for intracellular redox homeostasis. Notably, CC-CDs exhibit over 4000-fold enhanced water solubility relative to hydrophobic curcumin, which significantly amplifies their antioxidant potency and enables the dual action of near-complete bacterial eradication while preserving more than 98% cellular viability. Because of this biocompatibility, the composite hydrogel further facilitates macrophage polarization toward the regenerative M2 phenotype. <i>In vivo</i>, this has reduced the bacterial load by 90% within 24 h, increased anti-inflammatory cell recruitment 6-fold by day 4, and suppressed fibrotic markers by 91.8% while restoring 87.5% of the retinal signal amplitude by day 28. These findings highlight the synergistic capacity of the composite hydrogel for scar-free structural repair and visual function restoration through minimally invasive microenvironment modulation, establishing an alternative to conventional ophthalmic surgery.