Analysis of a Blend of Poly(acryamide) Gels with Varying Sodium Acrylate Formulations for Use in Vitreous Hydrogel Substitutes

Abstract

 

Purpose

 

We are developing vitreous substitutes that employ disulfide reversible cross-linkers, allowing the resultant copolymers to be reduced, dissolved, and purified ex-vivo and then re-gelled in situ. The mixture of the poly(acrylamide/sodium acrylate) brings improvements to previously reported poly(acrylamide) materials

 

Methods

 

Acrylamide [Am], acrylic acid neutralized to sodium acrylate [NaA], n-phenyl acrylamide [NPA] and bis-acrylol cystamine [BAC] were coplymerized using an ammonium persulfate/TEMED free radical polymerization system. The two formulations synthesized were #1= [72.5% Am: 20% NaA: 4.5% BAC: 3% NPA] and #2 = [82.5% Am: 10% NaA: 4.5% BAC: 3% NPA]. After reduction by dithiothreitol, the reconstituted copolymers were regelled at varying concentrations by oxidation. Physical, chemical and biocompatibility characterization was performed.

 

Results

 

The reduced copolymer #1 had a number average MW (Mn) of 285 kD, a polydispersity (PD) of 2.228, a hydrodynamic radius (Rh) of 21.19 nM and an intrinsic viscocity (IV) of 1.213 dl/g; and the reduced copolymer #2 had a Mn of 268kD, a PD of 1.814 a Rh of 14.76 nM and an IV of 0.491 dl/g. The copolymers were regelled at 1.25-1.75 w/w%. Refractive indices of the hydrogels ranged from 1.335-1.337. Graphs illustrating the rheology and biocompatibility are shown in the figures. Gels were optically transparent and similar to the vitreous in appearance.

 

Conclusions

 

Increasing the percentage of sodium acrylate acid results in lowering the critical concentration needed for gelling along with increasing the storage modulus. Moduli values cover the range of natural vitreous and biocompatibility was acceptable up to 15 mg/mL. These materials have advantages over our previously reported polyacrylamide hydrogels in their rheological properties, optical clarity and refractive index values and have potential for use as vitreous substitutes.

 

 

Storage modulus of a frequency scan of four copolymer formulations, two each of 10 and 20% NaA regelled copolymers. Values range from ~5-40 Pa.

 

 

MTT in vitro cell viability studies using human retinal epithelial cells (ARPE-19) were conducted on blends of acrylamide copolymers of 0-20% NaA. Cells were exposed for 70 hours to the polymers that were gelled in 10% FCS MEM. Staining was compared to cells grown in the absence of polymer.

 

Keywords: 764 vitreous substitutes • 762 vitreoretinal surgery