Stress Relaxation-Mediated Corneal Epithelial Repair Enabled by a Dynamic Hydrogel With Controlled Drug Release

Facilitating cell migration to injury sites is critical for repair. This process is significantly influenced by mechanotransduction, where cells sense and dynamically respond to extracellular mechanical cues, especially viscoelasticity. However, within viscoelastic microenvironments, the relative dominance of stiffness versus stress relaxation in directing migration remains unresolved. This necessitates biomaterials enabling independent tuning of viscoelasticity. In this study, we engineered a transparent hydrogel platform by synergistically crosslinking oxidized hyaluronic acid (oxi-HA) and gelatin methacryloyl (GelMA) via covalent bonds and dynamic Schiff base linkages. Precise modulation of the bond ratios achieved decoupled control over stiffness and stress relaxation. In vitro studies assessing fibroblast and epithelial cell migration on hydrogels with varying stiffness (2.3-11.5 kPa) and relaxation times (2.3-17.2 s) revealed substrate stress relaxation as the dominant cue governing migration. Furthermore, the cornea-like optical transparency (>90%), through the optimized formular, was achieved, and the hydrogel's drug release capacity was evaluated.