Porous Hydrogels Containing Cyclosporine-Loaded Polycaprolactone Nanoparticles as Delivery Carriers for Corneal Endothelial Cell Transplantation

Full-thickness corneal transplantation (penetrating keratoplasty, PK) is currently the most common way to treat corneas that are opacified owing to endothelial dysfunction. Because the supply of donor corneas is insufficient, corneal endothelial cell transplantation using expanded cultures is a potential alternative to PK. 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 sheet-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. Furthermore, immune rejection of allogeneic or xenogeneic materials is well known from cell transplantation biology. This project aims to address the drawbacks of existing cell sheet delivery systems by developing porous gelatin hydrogels containing cyclosporine-loaded polycaprolactone nanoparticles (CyA-loaded PCL NPs) as carriers for corneal endothelial regenerative medicine. In the first year, a study will be performed on the preparation, characterization, and biocompatibility assessment of biomaterial carriers. The next year will focus on the investigation of cellular structure and function of sheet grafts and drug biodistribution. In the final year of the study, the tissue reconstruction in an allogeneic model of rabbit corneal endothelial deficiency will be examined after intraocular grafting of cell sheets using porous gelatin hydrogels containing CyA-loaded PCL NPs. It is expected that the proposed delivery system in this project will be beneficial in helping people who are experiencing vision loss.

Project ID:PB10101-3616
External Project ID:NSC100-2628-E182-004-MY3