Glycosaminoglycan Modified Gelatin Scaffolds for Corneal Stromal Tissue Engineering

Every year, about 2 million people lose their vision due to cornea-related problems. In these cases, corneal grafts are applied, but donor shortage, graft rejection and disease transmission risks necessitate the development of artificial substitutes. A tissue-engineering scaffold, as a wound-healing guide for corneal stromal reconstruction, should be able to provide the physical and chemical environment that would facilitate the growth of keratocytes and deposition of newly synthesized extracellular matrix components upon remodeling. Gelatin is a naturally occurring biopolymer obtained by the thermal, chemical, or physical denaturation of collagen. In recent years, the use of gelatin has generated increasing interest in corneal cell transplantation and regenerative medicine. Chondroitin sulfate, one of the most physiologically important glycosaminoglycans, is an attractive natural-origin polymer present in corneal stromal layer. This component plays an essential role on wound healing and can be applied essentially in corneal stromal tissue engineering. The purpose of this study is to develop an effective scaffold for corneal stromal tissue engineering applications. The chondroitin sulfate is grafted onto porous gelatin scaffolds using a carbodiimide-mediated coupling reaction. In the first year of this project, the characteristics and in vitro compatibility of chondroitin sulfate-grafted gelatin scaffolds are investigated. The scaffolds are evaluated by determinations of porous structure, mechanical property, cross-linking degree, water content, chondroitin sulfate content, in vitro degradability, nutrient permeability, light transmittance and in vitro cytocompatibility. In the second year of this project, the effect of grafting yield on the biofunctionality of chondroitin sulfate-grafted gelatin scaffolds is investigated. The scaffolds are evaluated by means of cell/material interaction study and biomechanical test. In addition, an in vivo study of scaffold implantation in a rabbit model is undertaken to evaluate the efficacy of corneal stromal replacements composed of gelatin and chondroitin sulfate. It is expected that the proposed tissue-engineered technique in this project will be beneficial in helping people who are experiencing vision loss.

Project ID:PB9907-10766
External Project ID:NSC99-2221-E182-008