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

Authors

Mengyuan Shan, Yinghao Ding, Ping Lu, Fuqi Deng, Le Chang, Qin Zhou, Xinyu Li, He Tian, Qimiao Wang, Yi Dong, Zhimou Yang, Jiaqing Wang, Yan Wang

Published in

Bioactive materials. Volume 66. Pages 736-752. Epub Jul 18, 2026.

Abstract

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-^DFYIGSSSR), 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.

PMID:
42502320
Bibliographic data and abstract were imported from PubMed on 26 Jul 2026.

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