Corneal Inlay of Biomimetic Interpenetrating Network Hydrogel in Rabbit

Abstract

Purpose: : The Artificial Cornea Project at Stanford University has developed an interpenetrating network (IPN) hydrogel that is transparent and mimics the mechanical and physiological properties of current human corneal implants. This study reports on the biocompatibility of two sets of hydrogel polymer inlays surgically implanted into the corneal stroma of New Zealand rabbits.

Methods: : Rabbits were used to test for biocompatibility and nutrient diffusion through the polymer. Each animal was first anesthetized with 35 mg/kg Ketamine and 5 mg/kg Xylazine and prepared for surgery. The eye was proptosed and sterilized before creating a 180 or 250 micrometer thick corneal flap with a Hansatome or Amadeus II microkeratome, respectively. The IPN hydrogel inlay was inserted under the flap and sutured. Implants were 6 mm in diameter, and composed of poly(ethylene glycol)/poly(acrylic acid) with different terminal network linkages for the poly(ethylene glycol) component. The first group (n = 6) contained ester network linkages and second group (n = 3) contained acrylamide network linkages. The experimental eye was then treated with prednisolone 1% and topical antibiotic four times daily, for eight days following the surgery. The sutures were removed on the fifth day. Periodic examinations under anesthesia were performed until the animal was euthanized and the eye histologically sectioned. The animals were observed over a mean period of 122 days (range 91-163 days).

Results: : Photographic data comparing different subjects from the first and second hydrogel groups demonstrates marked improvement in the overall clarity of the overlying cornea and biocompatibility of the implants. The poly(ethylene glycol)/poly(acrylic acid) hydrogel prepared with ester network linkages resulted in a white opaqueness and inflammation directly above the inlay. In contrast, inlays and overlying cornea from the second set of implants containing acrylamide network linkages remain clear with no opacity or inflammation with healthy surface epithelium. We attribute these changes to the new hydrogel formulation and the concurrent reduction in polymer thickness used during surgery that resulted in increased nutrient diffusion and biocompatibility.

Conclusions: : We conclude that the poly(ethylene glycol)/poly(acrylic acid) interpenetrating hydrogel network corneal inlay based on acrylamide network linkages is biocompatible and allows for adequate nutrient diffusion to support surface epithelialization for up to 5 months.

Keywords: keratoprostheses • cornea: stroma and keratocytes • transplantation