An injectable shape-adaptive hydrogel system for subconjunctival injuries: In situ and permanently releases rapamycin to prevent fibrosis via promoting autophagy

Subconjunctival fibrosis (SCF) is a common and refractory eye disease that is a serious threat to vision. The severe side effects of existing drugs and low drug bioavailability due to the ocular barrier are major challenges in SCF treatment. Hence, there is an urgent need to explore safer and more effective strategies for administering anti-SCF drugs. Herein, an injectable and adaptable hydrogel system containing the antifibrotic drug rapamycin was fabricated to address this complex need. This system possesses moderate mechanical properties, self-healing and shape-adaptive capabilities, injectability, and biosafety. It is designed to promote autophagy by modulating the PI3K/AKT/mTOR/WIPI2 pathway, thereby inhibiting SCF. In vivo experiments utilizing a rat subconjunctival injury model indicated that in situ administration of this hydrogel system effectively inhibited SCF. This system constitutes a promising method for promoting autophagy to protect against SCF, which will foster its widespread application for other fibrotic diseases. An injective and adaptable hydrogel system with in situ and long-termed release of rapamycin was designed. This system will alleviate subconjunctival fibrosis via PI3K/AKT/mTOR signal mediated autophagy pathway. This method offers a great option for the treatment of subconjunctival fibrosis and can be employed as a therapeutic candidate for the other fibrosis diseases. [Display omitted] •An injectable hydrogel-based drug delivery platform was fabricated.•The in-situ gelation platform delivered rapamycin directly to injury sites with long-term efficacy.•The platform effectively inhibit subconjunctival fibrosis.•Rapamycin alleviated fibrosis via PI3K/AKT/mTOR signal promoting autophagy.