Toward the development of an artificial cornea: Improved stability of interpenetrating polymer networks

Abstract

A novel interpenetrating network (IPN) based on poly(ethylene glycol) (PEG) and poly(acrylic acid) was developed and its use as an artificial cornea was evaluated in vivo. The in vivo results of a first set of corneal inlays based on PEG-diacrylate precursor showed inflammation of the treated eyes and haze in the corneas. The insufficient biocompatibility could be correlated to poor long-term stability of the implant caused by hydrolytic degradation over time. Adapting the hydrogel chemistry by replacing hydrolysable acrylate functionalities with stable acrylamide functionalities was shown to increase the long-term stability of the resulting IPNs under hydrolytic conditions. This new set of hydrogel implants now shows increased biocompatibility in vivo. Rabbits with corneal inlay implants are healthy and have clear cornea and non-inflamed eyes for up to 6 months after implantation.

Biocompatibility of poly(ethylene glycol) and poly(acrylic acid) interpenetrating network hydrogel by intrastromal implantation in rabbit cornea

“…Their implant was also smaller (4 mm versus 6 mm). We previously reported the results of three rabbits with a 6 mm diameter implant with cornea remaining clear for up to 175 days [39]. Our current results show a higher rate of complications prior to 6 months as well as a high rate of corneal thinning and associated complications in implantations for longer than 6 months.…”

“…Poly(ethylene glycol) diacrylamide was synthesized using a protocol previously described [39]. A precursor solution of polyethylene glycol-diacrylamide (PEG-dAAm) (MW 8000) and a stock solution of photoinitiator, Irgacure 2959 (0.55 mol L −1 ) in acetone/water (50 v/v%), was prepared and a 5 M excess per PEG-endgroup was added to the polymer solution (50 w/v% in water).…”

“…Although both PEG and PAA are relatively weak materials, when combined to form a mesh-like network, they yield good mechanical properties, while retaining a water content of 70~90% and glucose diffusion coefficients similar to the cornea (~10 −6 cm 2 /s) [25, 38]. In previous work, PEG/PAA was shown to be non-cytotoxic [39]. In addition there had been encouraging results from a short term implantation of a small piece of this material as a corneal inlay in rabbits [40].…”

In vivo biocompatibility of two PEG/PAA interpenetrating polymer networks as corneal inlays following deep stromal pocket implantation

“…The IPN was then washed in phosphate buffer saline (PBS) until the pH and salt concentrations were equilibrated. To incorporate the second network, the single network hydrogel was removed from the mold and immersed overnight in an aqueous acrylic acid monomer solution (50 v/v %) containing photoinitiator stock solution (0.14 mmol per 1 ml acrylic acid) and triethyleneglycol dimethacrylate/tetra-ethyleneglycol diallylether as a crosslinking agent (0.04 mmol per 1 mL acrylic acid) [23]. The difference between the two IPNs used in this study was the choice of PEG based monomer.…”

T-style keratoprosthesis based on surface-modified poly (2-hydroxyethyl methacrylate) hydrogel for cornea repairs

“…Long-term vision restoration depends on adequate host integration, which is based on cell and tissue ingrowths into the spongy skirt and the retention of the artificial cornea in the host [19,45]. Uncontrolled cell growth and debris adsorption on the column's bottom should be discouraged to maintain its optical clarity, while the porous skirt of the Kpro should be encouraged to promote cell and tissue ingrowths.…”