Multifunctional Catechol‐Functionalized Cellulose Hydrogels for the Minimally Invasive Treatment of Acute Optic Nerve Injuries

Oxidative stress-induced retinal ganglion cell degeneration is a major pathological feature of acute optic nerve injury, yet current posterior-segment therapies are limited by poor local retention and repeated invasive administration. Here, we developed an injectable catechol-functionalized carboxymethyl cellulose hydrogel, CMCDA, as a bioadhesive and antioxidative intravitreal platform. Through dopamine grafting and oxidative crosslinking, CMCDA exhibited shear-thinning injectability, self-healing behavior, wet-tissue adhesion, controlled biodegradability, and good biocompatibility. In an optic nerve crush model, CMCDA significantly reduced retinal reactive oxygen species (ROS) accumulation, preserved retinal ganglion cells, promoted axonal regeneration, and attenuated microglial activation, with 7 wt% CMCDA showing the strongest therapeutic efficacy. Single-cell RNA sequencing further suggested that CMCDA reshaped the injured retinal microenvironment by suppressing apoptotic, oxidative-stress, and inflammatory pathways while supporting phototransduction-related programs. Importantly, these structural and molecular benefits were accompanied by improved visual function, as confirmed by visual cliff testing and electroretinography. Overall, CMCDA represents a multifunctional cellulose-based hydrogel platform for minimally invasive antioxidative neuroprotection, axonal repair, and functional recovery after optic nerve injury.