Minimally Invasive, High Transmittance, Adhesive and Antioxidative Hydrogel Complex for Treatments of Both Optic Neuropathy and Retinopathy.

Oxidative stress, primarily triggered by increased amount of reactive oxygen species (ROS), significantly contributes to the pathology of various retinal diseases. Herein, gelatin-caffeic acid (GelCA-2OH) and gelatin-caffeic acid oligomer (GelCAo-2OH) hydrogels are presented for intravitreal injections, aiming to effectively mitigate retinal oxidative damage. These advanced hydrogels are engineered with caffeic acid chemically conjugated to a gelatin backbone and stabilized using microbial transglutaminase for in situ crosslinking. Leveraging the antioxidative properties of caffeic acid, the hydrogels demonstrate enhanced injectability, self-healing capabilities, high transmittance, biocompatibility, and biodegradability, making them ideal for retinal applications. In vivo, the hydrogels significantly reduce ROS levels and promote cellular recovery across all layers of retinal neurons in a mouse retinal injury model. This highlights their transformative potential in regenerative medicine and biomedical engineering for both optic neuropathy and retinopathy. This approach provides the advantages of high concentration, extended durability, and reduced invasiveness while minimizing the risk of chorioretinal atrophy associated with subretinal injections. Overall, this study underscores the potential of caffeic acid-modified gelatin hydrogels as a novel therapeutic tool for oxidative stress in ocular tissues.