Dale J. Waters

Glucose-Permeable Interpenetrating Polymer Network Hydrogels for Corneal Implant Applications: A Pilot Study

Epithelialization of a keratoprosthesis requires that the implant material be sufficiently permeable to glucose. We have developed a poly(ethylene glycol)/poly(acrylic acid) (PEG/PAA) interpenetrating polymer network (IPN) hydrogel that can provide adequate passage of glucose from the aqueous humor to the epithelium in vivo. A series of PEG/PAA IPNs with varying PEG macromonomer molecular weights were synthesized and evaluated through swelling studies to determine their water content and diffusion experiments to assess their permeability to glucose. One of the PEG/PAA hydrogels prepared in this study had a glucose diffusion coefficient nearly identical to that of the human cornea (∼ 2.5 × 10− 6 cm2/sec). When implanted intrastromally in rabbit corneas, this hydrogel was retained and well-tolerated in 9 out of 10 cases for a period of 14 days. The retained hydrogels stayed optically clear and the epithelium remained intact and multilayered, indicating that the material facilitated glucose transport from the aqueous humor to the anterior part of the eye. The results from these experiments indicate that PEG/PAA hydrogels are promising candidates for corneal implant applications such as keratoprostheses and intracorneal lenses, and that the PEG/PAA IPN system in general is useful for creating permeable substrates for ophthalmic and other biomedical applications.

Interpenetrating polymer network hydrogel scaffolds for artificial cornea periphery.

Three-dimensional scaffolds based on inverted colloidal crystals (ICCs) were fabricated from sequentially polymerized interpenetrating polymer network (IPN) hydrogels of poly(ethyleneglycol) and poly(acrylic acid). This high-strength, high-water-content IPN hydrogel may be suitable for use in an artificial cornea application. Development of a highly porous, biointegrable region at the periphery of the artificial cornea device is critical to long-term retention of the implant. The ICC fabrication technique produced scaffolds with well-controlled, tunable pore and channel dimensions. When surface functionalized with extracellular matrix proteins, corneal fibroblasts were successfully cultured on IPN hydrogel scaffolds, demonstrating the feasibility of these gels as materials for the artificial cornea porous periphery. Porous hydrogels with and without cells were visualized non-invasively in the hydrated state using variable-pressure scanning electron microscopy.

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

We evaluated the biocompatibility of a poly(ethylene glycol) and poly(acrylic acid) (PEG/PAA) interpenetrating network hydrogel designed for artificial cornea in a rabbit model. PEG/PAA hydrogel measuring 6 mm in diameter was implanted in the corneal stroma of twelve rabbits. Stromal flaps were created with a microkeratome. Randomly, six rabbits were assigned to bear the implant for 2 months, two rabbits for 6 months, two rabbits for 9 months, one rabbit for 12 months, and one rabbit for 16 months. Rabbits were evaluated monthly. After the assigned period, eyes were enucleated, and corneas were processed for histology and immunohistochemistry. There were clear corneas in three of six rabbits that had implantation of hydrogel for 2 months. In the six rabbits with implant for 6 months or longer, the corneas remained clear in four. There was a high rate of epithelial defect and corneal thinning in these six rabbits. One planned 9-month rabbit developed extrusion of implant at 4 months. The cornea remained clear in the 16-month rabbit but histology revealed epithelial in-growth. Intrastromal implantation of PEG/PAA resulted in a high rate of long-term complications.