This Small Business Innovation Research Phase I submission proposes to design and produce nanofiber-based corneal tissue scaffolds to treat corneal diseases, the second most common cause of blindness worldwide, affecting 10-15 million people. This innovative approach uses electrospun mats from biocompatible polymers, which will be characterized for mechanical and optical properties. Candidate mats will be functionalized using a unique poly(acrylic) acid chemistry, conjugating extracellular matrix proteins laminin and fibronectin to the highly porous, high surface area nanofiber mats. Mats will then be sterilized, seeded with cultured human limbal stem cells, and attached to the scaffolds via laminin and fibronectin protein ligands. Cell viability and adhesion will be studied to determine the optimal transparent, biocompatible, pathogen-free, corneal scaffold for implantation in the eye. The broader impacts of this research include other ocular transplantation needs, such as corneal endothelial cell and retinal pigment epithelial cell transplantation (for macular degeneration), as well as tissue engineering for virtually all body tissues, from cardiac valve leaflets to tendon repair. Newer partial keratoplasty procedures, such as the rapidly evolving Descemet?s stripping endothelial keratoplasty (DSEK), would similarly benefit from a transparent tissue scaffold seeded with human endothelial cells. Worldwide, the need for healthy donor tissues far exceeds the available supply. This corneal transplant market is in excess of $22 billion annually worldwide. Experience gained from ocular bioengineering will translate into customization of other stem cells on nanofiber scaffolds for applications in diverse areas of the human body, broadening the impact of this technology for an aging population