Purpose. To investigate compositions of silica-collagen hybrid materials as potential artificial corneal substitutes, how these components affect the optical and biomechanical properties of the hybrids, and their biocompatibility in an organ culture model. Methods. Hybrid materials were created from different proportions of collagen and silica precursors and manufactured to specific dimensions. The microstructure of the materials was determined by electron microscopy and mechanical strength was measured by using suture pullout tests. The refractive index and transmittance were measured by using an Abbe refractometer and a spectrophotometer. Materials were implanted into rabbit corneas to determine their epithelialization in organ culture. Results. Scanning electron microscopy demonstrated that the hybrid material consisted of silica-encapsulating collagen fibrils. The refractive index ranged from 1.332 to 1.403 depending upon the composition and manufacturing characteristics. The rupture strength of a 3:1 (silica:collagen ratio by weight) rehydrated xerogel was 0.161 ± 0.073 N/mm (n = 12), while the hydrogels and 9:1 xerogel were too fragile for suturing. 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. Conclusions. Silica-collagen hybrid materials can be manufactured to specific dimensions to serve as a possible artificial corneal substitute. In preliminary studies, the materials had favorable optical, biomechanical, and biocompatibility properties necessary for replacing the corneal stroma.