A thermosensitive chitosan hydrogel enabled MnO₂ nanozyme delivery with NO release for enhanced corneal repair

Effective intervention during the early phases of alkali burns is crucial for preventing progressive ocular damage and persistent inflammation, necessitating multifunctional solutions beyond single-component therapies. In this study, we developed a thermosensitive hydrogel based on L-arginine-modified hydroxybutyl chitosan (HBC_Arg). The hydrogel remains liquid at room temperature for easy application and undergoes thermosensitive gelation upon reaching the ocular surface temperature, ensuring prolonged retention and enhanced drug efficacy. The L-arginine modification enables the hydrogel to release nitric oxide (NO), which plays a critical role in modulating immune responses and controlling excessive inflammation. Additionally, EPL@MnO₂ nanosheets were encapsulated within the hydrogel for extended-release and enhanced scavenging of reactive oxygen species (ROS), reducing oxidative stress and mitigating alkali burn-induced damage. In a rat ocular alkali burn model, the composite HBC_Arg/MnO₂ hydrogel significantly suppressed inflammation, promoted re-epithelialization, enhanced stromal healing, and prevented corneal vascularization and opacity. This multifunctional hydrogel offers a promising advanced therapeutic strategy for treating acute ocular alkali burns, providing potential improvements in visual outcomes and overall quality of life.