Alginate- and Hyaluronic Acid-Based Hydrogels as Vitreous Substitutes: An In Vitro Evaluation

Purpose: To study alginate- and hyaluronic acid-based hydrogels in vitro as vitreous substitutes. Methods: Biopolymeric hydrogels based on high-molecular alginate (0.5% and 1.0%) and hyaluronic acid (1.0% and Healaflow) were compared with extracted human vitreous bodies and silicone oil (SIL-5000) regarding their optical properties (refractive index, transmission) and viscoelastic characteristics (storage modulus G', loss modulus G"). The cytotoxic (metabolic activity, apoptosis) and antiproliferative profiles were determined using cultured human fibroblasts, ARPE-19, and photoreceptor cells. The hydrogel systems were applied to human fetal retinal pigment epithelial cells cultured for two months until maximum transepithelial electrical resistance (TEER) to investigate the effect of the gel matrices on tight junctions using TEER measurements and immunostainings against the tight junction protein ZO-1. Results: Tested alginate- and hyaluronic acid-based hydrogels resembled the natural refractive index of human vitreous bodies (1.3356-1.3360) in contrast to SIL-5000 (1.4034) and showed high optical transparency (>90%) within the visible light region. The biopolymeric hydrogels exhibited viscoelastic properties similar to juvenile vitreous bodies with G'>G" adjustable via different gelation times, contrary to SIL-5000 (G'<G"). The metabolic activity, apoptosis and tight junctions of all tested ocular cells were unaffected by the alginate- and hyaluronic acid-based vitreous substitutes. Conclusions: The present in vitro study demonstrates good optical, viscoelastic, and biocompatible properties of alginate- and hyaluronic acid-based hydrogels required for their use as vitreous substitutes. Translational Relevance: Biopolymer-based hydrogels represent a promising vitreous replacement strategy to treat vitreoretinal diseases.