In situ spermidine-integrated dynamic hyaluronic acid-based hydrogels platforms for anti-inflammation and anti-fibrosis in subconjunctival injuries.

Subconjunctival injuries pose significant risks of vision impairment through inflammation and fibrosis. Current therapeutic strategies are hampered by suboptimal drug delivery efficiency, cytotoxic risks, and an inability to address dynamic pathophysiology due to rigid degradation profiles and poor microenvironmental responsiveness. Consequently, biosafe, efficacious treatments with dual anti-inflammatory and anti-fibrotic capabilities represent a critical unmet need. Hyaluronic acid, due to its safety and naturalness, has been investigated as a functional hydrogel dressing. Herein, we presented an innovative dual-crosslinked hyaluronic acid-based dynamic hydrogel as the carrier, which immobilizes and releases spermidine (SPD) molecules via dynamic bonds. The engineered hydrogel demonstrates injectability, self-healing capacity, and controlled, sustained release properties, enabling conformal tissue integration and continuous participation in the healing cascade. This system exhibits synergistic anti-inflammatory and antioxidant functionality. In vivo validation confirmed significant attenuation of pro-inflammatory signaling molecules and cytokines, coupled with suppression of fibrotic progression via collagen deposition modulation. This work establishes a novel therapeutic paradigm for subconjunctival injury management and provides foundational insights for addressing broader ocular surface fibrotic pathologies.