Self-assembling biomimetic peptide hydrogel regulates tissue homeostasis to promote repair of persistent corneal epithelial defects

Persistent corneal epithelial defects (PCED) remain a significant clinical challenge due to rapid tear turnover, blinking-induced shear stress, and a protease-rich ocular surface that limit the efficacy of soluble bioactive factors. We report a dual-functional self-assembling peptide hydrogel, mIGF-Gel (Biotin- D FYIGSSSR), incorporating the adhesion motif YIGSR derived from laminin and the SSSR bioactive motif derived from insulin-like growth factor 1 (IGF-1) in a single design. The peptide forms a β-sheet-rich nanofibrous hydrogel with shear-thinning, viscoelastic, and self-recovering properties, enabling adaptation to the dynamic ocular surface. Compared with recombinant IGF-1, mIGF-Gel retains IGF-1-like bioactivity while providing enhanced proteolytic stability, ocular retention, and local delivery efficiency. Mechanistically, mIGF-Gel activates IGF-1 receptor-mediated PI3K/AKT signaling to promote corneal epithelial cell proliferation, migration, and survival. In an acute corneal injury model, topical mIGF-Gel accelerates re-epithelialization and improves epithelial repair quality. In a dexamethasone-suppressed delayed-healing model, once-daily administration achieves therapeutic outcomes comparable to three-times-daily IGF-1, while further enhancing epithelial stratification, basement membrane reconstruction, and early nerve repair. Collectively, these results establish mIGF-Gel as a bioactive, wound-adaptive peptide hydrogel that overcomes pharmacokinetic limitations and holds translational potential for the treatment of persistent epithelial defects, as demonstrated in both acute injury and a PCED-mimetic delayed-healing model.