A bioactivity-enhanced thermosensitive amnion-derived hydrogel with sustained IGF-1 release: A multitargeted and efficient strategy for corneal injury repair.

Corneal alkali burn (CAB) remains difficult to treat because rapid tear clearance limits topical drug exposure, while the injured cornea develops a complex microenvironment involving inflammation, neovascularization, fibrosis, epithelial barrier loss, and impaired nerve repair. Here, we developed a human amniotic membrane-derived thermosensitive hydrogel (hAMgel) and loaded it with insulin-like growth factor-1 (IGF-1) to create a bioactive sustained-release system (IGF1@hAMgel) for CAB repair. The hAMgel transformed from a flowable precursor into a semi-transparent film on the ocular surface within 1-2 min and IGF1@hAMgel released approximately 90% of loaded IGF-1 over 24 h, with corneal IGF-1 concentration peaking at 2 h post-dose (378.5 pg/mg protein) and remaining detectable over 24 h, supporting sustained topical exposure. In a rat CAB model, IGF1@hAMgel accelerated epithelial healing, reducing the fluorescein-stained area from 31.34 ± 2.83% in controls to 16.78 ± 2.87% at day 1. By day 14, IGF1@hAMgel reduced corneal opacity (0.67 ± 0.52 vs. 4.00 ± 0.00), resolved edema with central corneal thickness approaching baseline (187.7 ± 16.31 μm vs. 178.3 ± 5.89 μm), suppressed neovascularization (CD31-positive area 4.46 ± 1.69% vs. 24.33 ± 2.07%), and promoted corneal nerve regeneration. Proteomic analysis showed that hAMgel retained abundant extracellular matrix(ECM) components, including collagens, Lumican, and fibronectin, together with repair-related and immunomodulatory proteins. These findings identify IGF1@hAMgel as a sutureless, eye-drop-like bioactive ECM platform that integrates growth-factor delivery with amnion-derived reparative cues for multitargeted ocular surface repair.