Abstract: | Corneal blindness is explained by a large reduction in vision loss caused by acute and chronic corneal diseases and/or disorders. Due to the severe unavailability of donor corneas, immune rejection, and the side effects of keratoprosthesis (KPro), vision-impaired patients are often unable to restore their vision. Corneal tissue engineering appears to be a promising method using natural polymers made from different layers of corneal cells such as epithelium, stroma, and endothelium or full tissue equivalents. Proteins and polysaccharides are able to mimic the chemical composition of the native extracellular matrix (ECM), which has been extensively studied for corneal tissue engineering. Additionally, protein-based materials are highly favored in corneal regenerative therapy as they have the proper cell-binding sites for cell adhesion, corneal innervation regeneration, and oxidative stress suppression, while polysaccharide-based materials can also promote cell proliferation and adhesion as well as ocular permeability. Herein, a comprehensive review of various biomaterials based on natural proteins (fibrin, fibrinogen, silk fibroin, collagen, gelatin, and serum albumin) and polysaccharides (chitin, chitosan, hyaluronic acid, alginate, cellulose, and gellan gum) for corneal tissue engineering are provided. The protein-polysaccharide biomaterials are mainly used in the form of hydrogels, films, scaffolds, sutures, eye drops, nanocarriers, and nanocapsules to treat ocular diseases that cause blindness, such as corneal wounds, corneal ulcers, Goldenhar syndrome, corneal endothelium and stroma defects, corneal neovascularization, etc. In this review, insight is provided into recent developments in the areas of biomaterial design, cross-linking strategy, corneal cell selection, and frontiers that are expected to offer researchers support and creativity in the development of corneal regenerative medicine. |