Gelatin Methacrylate as an Enzyme-Controlled Release Vehicle of Hyaluronic Acid for the Treatment of Recurrent Corneal Erosion

Abstract

Recurrent corneal erosion (RCE) is a condition where the superficial corneal epithelial cells sporadically shed because of poor attachment to the underlying basement membrane, resulting in pain and discomfort. RCE-afflicted corneas exhibit elevated biological factors and enzymes, such as matrix metalloproteinase (MMP)-9. Soft bandage contact lenses (BCLs) are a commonly recommended treatment as they permit continued vision during recovery. However, they do not outperform alternative treatments as they currently lack active ingredients for ocular surface repair. Development of BCLs with a sustained release of active ingredients to promote RCE wound healing over an extended period of time would be clinically valuable. We fabricated gelatin methacrylate (GelMA) hydrogels with MMP-9-triggered controlled release for further BCL development. GelMA disks were characterized to determine the optimal concentration and methacrylation degree for sustained release in the presence of MMP-9. The chosen active ingredient, 60 kDa hyaluronic acid (HA), was verified to promote wound healing in rabbit corneal epithelial cell and human corneal epithelial cell wound assays. The active ingredient was loaded into GelMA hydrogels, and the bioavailability of the vehicle was determined. The GelMA hydrogels revealed a tunable profile for diffusion and enzyme-mediated controlled release of a model molecule. The 60 kDa HA-loaded GelMA disks showed improvement in wound healing at HA loadings of 150 and 250 μg by improving the wound healing rates by 28% (68.7% wound closure) and 26% (67.9% wound closure), respectively, compared to the control (50.5% wound closure) at 24 h. The HA-loaded GelMA disks with 150 and 250 μg HA also exhibited shortened wound closure time of 75 h compared to >147 h with a bolus daily delivery of HA for wound closure. Overall, we demonstrated that the fabricated GelMA hydrogels offered an enzyme-triggered option as a sustained release material for future RCE treatments.