An optically and biomechanically corneal tissue-matched dual-crosslinkable hydrogel for cell-free remodeling of the corneal stroma

Corneal trauma is a leading cause of visual impairment and blindness worldwide, yet corneal stromal repair and regeneration remain a significant challenge in ophthalmology because of its limited intrinsic repair capacity and fibrotic scar formation during healing process. Here we report an optically and biomechanically corneal tissue-matched in situ dual-crosslinkable hydrogel that enables cell-free corneal stromal remodeling. By integrating dynamic covalent crosslinking with static photocrosslinking strategy, the optimized hydrogel-based substitute achieved high optical transparency, a refractive index of approximately 1.35, and an elastic modulus of 83.8 ± 13.4 kPa, closely resembling the properties of the healthy human cornea. In a rabbit model of deep corneal defects, the optimized in situ -forming hydrogel adapted to the defect geometry, adhered stably to the wound bed, recapitulated the optical and biomechanical properties of the native cornea, and supported scarless corneal stromal remodeling. Incorporation of the antimicrobial peptide HHC36 further endowed the hydrogel with robust antibacterial activity without compromising its optical and biomechanical properties. In a rabbit model of P. aeruginosa –infected deep corneal defects, the HHC36-loaded in situ -forming hydrogel effectively mitigated clinical signs of infection and substantially promoted corneal stromal remodeling within 30 days while reducing fibrosis. Overall, this optically and biomechanically corneal tissue-matched in situ dual-crosslinkable hydrogel might be a promising substitute for corneal stromal remodeling.