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K. Hori, C. Sotozono, K. Yamasaki, M. Ozeki, Y. Kimura, Y. Tabata, S. Kinoshita; Gelatin Hydrogel as Controlled–Release Carrier of Growth Factor on Ocular Surface . Invest. Ophthalmol. Vis. Sci. 2005;46(13):2153.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: We have prepared several variations of biodegradable hydrogels from gelatin that has the ability to physicochemically interact with some growth factors, enabling their controlled release, have thereby successfully enhanced growth factor biological activities. Growth factor is released as a result of hydrogel degradation. The object of this study is to investigate the feasibility of using gelatin hydrogel for the controlled release of growth factor on the ocular surface. Methods: We used epidermal growth factor (EGF) as a representative growth factor. A biodegradable hydrogel was prepared from a cationic derivative of gelatin that can interact with EGF. The cationized gelatin hydrogel, with 125I–labelled EGF incorporated, was placed in the conjunctival sacs of mice, and the residual radiation was measured at different time intervals to evaluate the in vivo profile of EGF release. Hydrogel incorporating 5 µg of EGF was placed on a round defect of rabbit cornea (177 mm2) and the defect area was measured by image analyzing software to evaluate the healing process (n=6). In addition, epithelial proliferation was assessed immunohistochemically by counting the number of Ki67–positive cells. EGF–free cationized gelatin hydrogel was used as control. Results: Cationized gelatin hydrogel incorporating EGF remained over 7 days in the conjunctival sacs. When hydrogel incorporating EGF (E+) was applied to the corneal epithelial defect, defect area decreased to 10.0 ± 13.7 mm2 at 4 days after wounding; this was a significantly greater decrease than that seen with EGF–free hydrogel (E–) (49.3 ± 22.4 mm2) (p=0.01). The number of Ki67–positive cells at the peripheral unwounded cornea was 11 (E+) and 1.4 (E–) cells/mm. Conclusions: Cationized gelatin hydrogel is a promising carrier for controlled release of biologically active EGF on the ocular surface. This growth factor controlled–release system can be applied to other growth factors and may provide a novel treatment option for severe ocular surface diseases.
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