April 2010
Volume 51, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2010
In-situ Cross-Linking, Injectable Hydrogel for Lens and Vitreous Substitutes
Author Affiliations & Notes
  • H. Du
    Research,
    VA Medical Center, St Louis, Missouri
    Ophthalmology & Visual Sciences, Washington University, School of Medicine, St. Louis, Missouri
  • P. D. Hamilton
    Research,
    VA Medical Center, St Louis, Missouri
  • N. Ravi
    Executive Branch,
    VA Medical Center, St Louis, Missouri
    Energy, Enviromental and Chemical Engineering, Washington University, St. Louis, Missouri
  • Footnotes
    Commercial Relationships  H. Du, None; P.D. Hamilton, None; N. Ravi, None.
  • Footnotes
    Support  This research was supported by a Department of Veterans Affairs review grant to Dr. Nathan Ravi, Research to Prevent Blindness, Inc., NIH Core Grant (P30 EY 02687), and Washington University.
Investigative Ophthalmology & Visual Science April 2010, Vol.51, 3607. doi:
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    • Get Citation

      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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Abstract
 
Purpose:
 

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.

 
Methods:
 

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.

 
Results:
 

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).

 
Conclusions:
 

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.  

 
Keywords: vitreous substitutes • accommodation • vitreoretinal surgery 
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