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K. E. Swindle, P. D. Hamilton, N. Ravi; Development of a Biomimetic Hydrogel Vitreous Substitute That Forms in situ. Invest. Ophthalmol. Vis. Sci. 2008;49(13):5967.
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Due to the successful trials of our previous formulation, we developed more biocompatible poly(acrylic acid) hydrogels that form in situ under physiological conditions as potential vitreous substitutes. The biomimetic hydrogel formulation was optimized to match the refractive index and viscoelastic properties of the natural vitreous humor.
Stat-Ease Design Expert 6.0 (Minneapolis, MN) was used to develop a crossed model to optimize the properties of the vitreous substitute. Various poly(acrylic acid) hydrogel formulations were synthesized containing a reversible disulfide crosslinker and a hydrophobic comonomer. The hydrophobic comonomer, crosslinker, and hydrogel concentrations were varied. The refractive index and rheological properties from the young porcine vitreous were used as a model for optimizing the hydrogel formulation. The storage and loss moduli of the hydrogels were determined using a Vilastic 3 capillary rheometer (Houston, TX) holding frequency or shear rate constant. The refractive indices of the hydrogels were determined using an Abbe refractometer. In vitro toxicity of the hydrogels was determined using retinal pigment epithelial cells.
The storage and loss moduli of the hydrogels were compared to those of the porcine vitreous. Only the formulations with a higher storage than loss modulus exhibited gel-like behavior, similar to the vitreous humor. Decreasing the polymer concentration in the hydrogel optimized the refractive index and toxicity. Conversely, the desired viscoelastic properties were obtained by increasing the polymer concentration in the hydrogel. The statistical model was used to analyze the experimental results and solve for an optimal vitreous substitute formulation that would closely match both the refractive index and viscoelastic properties of the natural vitreous humor using surface response methodology.
Statistical experimental design enabled rapid screening of hydrogel formulations as candidate vitreous substitutes. The optimal formulation will be tested in vivo in future work.
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