Tailoring Silk Fibroin-Based Hydrogels for Enhanced Corneal Epithelial Repair

The therapeutic potential of silk fibroin (SF) and hyaluronic acid (HA) composite hydrogels for corneal epithelial wound healing was assessed, focusing on the molecular weight of SF related to outcomes. Initially, SF of varying molecular weights was analyzed, and a medium molecular weight (M-SF; 10–72 kDa, average 40 kDa) was identified as most effective in promoting cell proliferation, attachment, and migration in various assays. A hydrogel formulation, H-SF/HA gel@M-SF, was then developed by incorporating M-SF (10–72 kDa, average 40 kDa) into a base hydrogel composed of high molecular weight SF (H-SF; 18–100 kDa, average 60 kDa) and HA. The physicochemical properties of the hydrogels, including pH balance, extensibility, and swelling rate, were characterized. The biological functions of the hydrogels were evaluated by using human corneal epithelial (HCE-T) cells and a mouse corneal injury model. H-SF/HA gel@M-SF exhibited supported enhanced expression of key genes associated with corneal repair, such as NOTCH I, GSK3β, ACTG, and VCL when compared with a serum-free medium. In vivo studies using mice demonstrated that H-SF/HA gel@M-SF achieved complete wound closure within 48 h, outperforming the H-SF/HA gel. These results underscore the significance of the SF molecular weight and concentration in hydrogel design and highlight the potential of H-SF/HA gel@M-SF for ophthalmic applications.