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K. E. Swindle, P. D. Hamilton, Y.-B. Shui, D. C. Beebe, S. Kaushal, N. Ravi; Evaluation of an in situ Forming Hydrogel as a Vitreous Substitute. Invest. Ophthalmol. Vis. Sci. 2007;48(13):2247.
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We developed polymeric hydrogels that form in situ as potential vitreous substitutes. The use of a disulfide crosslinker enables the polymer to be injected as a liquid and form a gel by reacting with oxygen. Rheological testing was performed to compare the viscoelastic properties of the hydrogels to that of the porcine vitreous and the polymers were gelled under simulated physiological conditions.
Hydrogels were prepared as previously described (Aliyar et al., Biomacromolecules, 6, 204, 2005). The polymer formulation was modified to contain 4.5% disulfide crosslinker and 3.0% hydrophobic monomer. The molecular weight was determined using Viscotek HPLC-GPC. Hydrogels were prepared at 2% and 3% (w/w) concentrations in water. Gelation was tested in simulated physiological conditions by equilibrating the reduced polymer in 18 mm Spectra/Por dialysis tubing in DPBS under a controlled oxygen concentration of 5%. The mechanical properties of the porcine vitreous and hydrogels were determined using a Vilastic-3 oscillatory capillary tube rheometer.
The number average molecular weight of the polymer was 207.2 kDa with 0% below a molecular weight of 10 kDa. The hydrogel formulation gelled in 1 hour under simulated physiological conditions in the dialysis tubing. The storage and loss modulus of the 2% hydrogel formulation matched those of the natural porcine vitreous.
This in situ forming hydrogel has viscoelastic properties close to that of the natural vitreous and gels in 1 hour at a reduced oxygen concentration similar to that of the eye. Previous in vitro toxicity tests coupled with the current in vitro gelling studies indicate that this hydrogel formulation will be a good candidate for in vivo testing.
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