Tissue-engineered artificial corneas could eventually replace cadaveric corneal transplantation, enabling sight-restoring procedures to many who do not have access to eye banking facilities. We investigated compositions of silica–collagen hybrid materials as potential artificial corneal substitutes. Hybrid materials were created from different proportions of collagen and silica precursors and manufactured to specific dimensions. Materials were implanted into animal corneas to determine if they supported epithelialization of their surface. The refractive indices of the hybrid materials ranged from 1.33 to 1.40 depending upon the composition and manufacturing characteristics. Transmissibility of 3:1 (silica:collagen ratio by weight) and 9:1 rehydrated xerogels was similar to that of normal rabbit corneas. Re-epithelialization of 5- to 6-mm-wide rabbit corneal epithelial defects was complete in 5.5 ± 2.4 days (n = 6), with evidence of epithelial stratification. Silica–collagen hybrid materials have properties that are promising for use as an artificial corneal substitute. Additional studies are required to determine long-term outcomes in vivo.