Porous Gelatin Carriers for Rabbit Corneal Cell Sheet Delivery and Therapy

Human corneal endothelium has essentially no regenerative capacity. When the cell density is less than 500 cells/mm2, the endothelium no longer functions, causing irreversible corneal edema and loss of visual acuity. Because the supply of donor corneas is insufficient, corneal endothelial cell transplantation using expanded cultures is a potential alternative to penetrating keratoplasty. Numerous investigators have focused on engineering corneal endothelial replacements by seeding and culturing cells on different substrates. However, the approaches involving the use of culture substrates may be responsible for several postoperative complications. To overcome the permanent residence of foreign substrates in the host, we have presented a novel cell-based strategy for corneal endothelial reconstruction. The results of our previous study indicate the application of gelatin carriers for cell sheet transplantation is capable of improving the graft-host integration in a xenogeneic model. However, the implantation of gelatin membranes with dense structure in the anterior chamber may cause elevated intraocular pressure and decreased glucose transport. This project aims to address the drawbacks of existing cell sheet delivery systems by developing a highly efficient carrier. In the first year of this project, porous gelatin hydrogels will be prepared by lyophilization and carbodiimide cross-linking. The effect of porous structure and cross-linking degree on the functionality of gelatin carriers for cell sheet delivery will be investigated to optimize the preparation conditions. In the second year of this project, the carrier-cell sheet construct-mediated tissue remodeling will be examined in an allogeneic model of rabbit corneal endothelial deficiency. A long-term (i.e., 12 months) study will be undertaken to evaluate the efficacy of using porous gelatin carriers for corneal regenerative medicine. It is expected that the proposed cell sheet transplantation and therapy technique in this project will be beneficial in helping people who are experiencing vision loss.

Project ID:PB9808-2372
External Project ID:NSC98-2221-E182-012