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H. Du, P. D. Hamilton, N. Ravi; In-situ Cross-Linking, Injectable Hydrogel for Lens and Vitreous Substitutes. Invest. Ophthalmol. Vis. Sci. 2010;51(13):3607.
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We are developing in-situ cross-linking, injectable hydrogels for accommodative lens materials and vitreous substitutes using biopolymers based on deacylated gellan, which possesses double-helical structure, mimicking the function of the native collagen found in human vitreous.
Deacylated gellan (Gelzan, Sigma, St. Louis, MO) was thiolated by the covalent attachment of cysteine via thiol and carbodiimide chemistry [J. Pharm. Sci. 92: 1234-1241, 2003]. Thiolated gellan in aqueous solution forms a hydrogel in physiological medium at room temperature (RT) upon exposure to air by oxidation of the thiol groups (-SH) into disulfide bonds (-S-S-). The double-helical structure of the gellan molecules are thus covalently connected via disulfide bonds and could provide a hydrogel substitute for artificial vitreous and accommodative lens materials.
Thiolated gellan was successfully obtained without disrupting the double-helical structure of native gellan. A transparent, injectable hydrogel formed at 0.2 wt% within 15 min in physiological medium at RT. The resulting hydrogel was water-insoluble and thermally stable. The mechanical properties (storage modulus and loss modulus) can be engineered to match that of human ophthalmic materials by adjusting the polymer concentration and/or degree of the thiol substitution (Figure 1).
An in-situ cross-linking, injectable, and transparent hydrogel was obtained in physiological medium at low concentrations with reasonable gelation time at RT. By covalently cross-linking the gellan via disulfide bonds, the hydrogel is water-insoluble, thermally stable and is expected to be more resistant to degradation in vivo. These characteristics make the thiolated gellan a promising candidate for long-term lens materials and vitreous substitutes.
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