Characterization of Poly(Ethylene Glycol)–Poly(Acrylic Acid) (PEG–PAA) Double Networks Designed for Corneal Implant Applications

Abstract

Abstract: : Purpose: To assess the potential of poly(ethylene glycol)–poly(acrylic acid) (PEG–PAA) double network hydrogels for application as a corneal implant material on the basis of three criteria: tensile strength, permeability to glucose, and capacity for cellular adhesion. Methods: The mechanical properties of optically clear PEG–PAA double networks (water content 80%) prepared by two–step photopolymerization were measured using a MTS Bionix 100 materials testing device. Permeability of PEG–PAA to glucose was determined using a modified Boyden chamber apparatus. Poly(2–hydroxyethylmethacrylate) (pHEMA) hydrogels (water content 40%) prepared by photoinitiation served as controls for both mechanical strength and permeability tests. Cell adhesion to PEG–PAA, and PEG–PAA covalently–modified with collagen type I, as well as tissue–culture polystyrene was assessed using a primary rabbit corneal epithelial cell line which was cultured in DMEM/F12 media with 5% FBS, 0.5% ITS, and 1% Pen/Strep and seeded on substrates at a concentration of 1.0 x 10⁵ cells/cm². Cell morphology and spreading were evaluated by inverted phase contrast microscopy at designated intervals over 5 days. Results: PEG–PAA (modulus at break 3.1 MPa, max. stress = 1.07 ± 0.13 MPa, max. strain = 0.93 ± 0.08) was 10 times stronger than PEG or PAA alone and comparable to that of pHEMA (modulus at break 1.1 MPa, max. stress = 0.96 ± 0.15 MPa, max. strain = 1.20 ± 0.07). Permeability of PEG–PAA to glucose (diffusion coefficient D_PEG–PAA = 0.9 ±0.1 x 10^–6 cm²/s) was 2 times less than that of PEG and PAA single networks but 30 times more than that of pHEMA (D_PHEMA = 3.0 ± 0.7 x 10^–8 cm²/s). Cell spreading assays showed no spreading of cells on unmodified PEG–PAA. In contrast, cells exhibited excellent spreading (>75%) on collagen–bound PEG–PAA within 2 hours, achieved confluency within 48 hours, and had migrated over the remainder of the unseeded surface by day 5. Morphology of cells spreading on collagen–bound PEG–PAA was comparable to that of cells seeded on tissue–culture polystyrene. Conclusions:PEG–PAA double networks are mechanically strong, permeable, and can be modified to facilitate corneal epithelial cell growth on their surface. These properties make PEG–PAA double networks promising materials for corneal implant applications such as keraprostheses and corneal onlays for correction of refractive error.

Keywords: keratoprostheses • cornea: epithelium • nutritional factors