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

Abstract

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.

Vitreous Substitutes from Bench to the Operating Room in a Translational Approach: Review and Future Endeavors in Vitreoretinal Surgery

“…The low toxicity of hydrogels-based biomaterials can avoid the extraction of the employed current tamponades (e.g., SiOs, HSiOs) after the chorioretinal adhesion has occurred. Many natural and synthetic polymers showed promising results as hydrophilic tamponades such as HA [ 182 , 183 , 184 , 185 , 186 , 187 , 188 ], alginate [ 183 , 189 ], collagen [ 187 , 190 ], gellan [ 191 , 192 ], chitosan [ 188 , 189 , 193 ], polyvinyl alcohol methacrylate [ 194 ], polyvinyl alcohol [ 195 , 196 , 197 , 198 , 199 ], poly (ethylene glycol) [ 200 ], acrylic acid [ 201 ], acrylamide [ 185 , 202 ], poly N-acryloyl [ 203 ] and glycinamide-polycarboxybetaine acrylamide [ 203 ]. However, the clinical application of many of the previously described materials has been hampered by their lack of transparency, deviating refractive indices, degradation, or poor biocompatibility, and even the toxicity of the crosslinking agents.…”

Advances in Polysaccharide- and Synthetic Polymer-Based Vitreous Substitutes

“…Vitreous substitutes must be transparent and permeable. The natural vitreous maintains the shape of the eye by behaving as a viscoelastic fluid or gel [ 12 , 21 ] and a vitreous substitute must mimic this. An ideal vitreous substitute should also not degrade with time [ 15 ].…”

“…In vivo rabbit studies of the hydrogel indicated no inflammation or toxicity after 1 week [ 108 ]. Recently, Davis et al [ 21 ] incorporated acrylic acid into the hydrogel formulation. Various concentrations of this hydrogel were developed and characterised.…”

Synthesis, and antimicrobial and anticancer activities of sodium acrylate copolymers

“…[18][19][20] There are also subjects studied differently in the literature. 21,22 According to biocompatibility testing in tissue culture with poly(acrylic acid) retinal pigment epithelial cells (ARPE-19), it was found to be a non-toxic polymer of 10 mg/mL compared to controls and polymers with higher concentrations. Unlike the previously reported copolyacrylamide hydrogels, these hydrogels remained optically clean and gelled at low concentrations and have the potential to be used as vitreous substitutes.…”

“…Unlike the previously reported copolyacrylamide hydrogels, these hydrogels remained optically clean and gelled at low concentrations and have the potential to be used as vitreous substitutes. 21 In previous studies, we have investigated the efficacy of different types of antimicrobial polymers against different pathogenic microorganisms. [22][23][24][25][26][27][28][29] This polymer differs from the existing antimicrobial polymers in that it removes harmful properties due to dermatophyte fungi found in the skin, nails and hair.…”