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J.-Y. Lai; Development of Cross-Linked Gelatin Membranes as Potential Delivery Carries for Retinal Tissue Engineering Applications. Invest. Ophthalmol. Vis. Sci. 2010;51(13):5253.
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Retinitis pigmentosa and age-related macular degeneration are clinical entities that cause reduced visual acuity. This study aims to investigate the possibility of using cross-linked gelatin membranes as tissue carriers for retinal sheet delivery applications.
The gelatin membranes were prepared by solution casting method, and were subsequently modified by physical or chemical cross-linking treatment. Ninhydrin assays were used to determine the extent of cross-linking. The effect of cross-linking on mechanical properties was investigated by tensile testing. In addition, the degradability was studied by incubating the gelatin carriers at 37°C in balanced salt solution containing collagenase. The interaction between cross-linked gelatin materials and human retinal pigment epithelial cells was analyzed for indication of cytocompatibility. Retinal sheet delivery studies using various gelatin carriers were performed to evaluate the easiness of handling in surgery.
In comparison with physical cross-linking approaches (i.e., UV irradiation and dehydrothermal treatment), chemical cross-linking methods involving the use of formaldehyde and carbodiimide could produce gelatin membranes with higher extent of cross-linking. While the physically modified gelatin materials were unstable, the chemically cross-linked counterparts had strong mechanical strength and exhibited good degradation resistance. The results indicate that the gelatin carriers treated with formaldehyde and carbodiimide may provide temporary support for retinal sheet delivery and tissue regeneration. However, it was noted that the cells exposed to formaldehyde cross-linked gelatins had relatively higher lactate dehydrogenase activity, cytotoxicity, and interleukin-1β and interleukin-6 levels than did those to carbodiimide cross-linked samples. In contrast to other three types of cross-linked gelatins, the carriers modified with carbodiimide showed better capability for delivering intact retinal sheets.
The present study suggests that carbodiimide cross-linked gelatin carriers may have great potential for retinal tissue engineering.
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