Poly(acrylamide co-acrylic acid) for use as an in situ gelling vitreous substitute

Our objective is to improve on our previous work developing thiol-containing water-soluble copolyacrylamides that form hydrogels in situ for use as vitreous substitutes. In this study, we evaluate the incorporation of acrylic acid by varying the feed ratio of acrylic acid monomer from 0 to 40 mol% in combination with acrylamide, and bis-acryloylcystamine as the reversible cross-linker. After polymerization, the formed copolymer hydrogels were reduced with dithiothreitol to cleave the disulfide cross-linkers. Purified, lyophilized copolymers were made in a concentration range of 12.5-17.5 mg/mL (polymer in deionized water) and were gelled by oxidation. Chemical, physical, optical, and rheological characterizations along with in vitro biocompatibility studies were performed using thiazolyl blue and Electric Cell-substrate Impedance Sensing. Increasing the percentage of acrylic acid caused the polymer to gel at 12.5 mg/mL as opposed to 20 mg/mL without acrylic acid. Storage modulus values covered the range of natural vitreous (1-108 Pa). Biocompatibility testing in tissue culture with retinal pigment epithelial cells (ARPE-19) showed no toxicity at 10 mg/mL or less when compared to controls, higher concentrations. In contrast to our previously reported copolyacrylamide hydrogels, these hydrogels remain optically clear and gel at lower concentrations and have the potential for use as vitreous substitutes.