In-Situ Repair of Corneal Stroma using A Light-Curable Hydrogel from Porcine Corneal Extracellular Matrix

Abstract

Purpose : A Light-curable COrnea Matrix (LC-COMatrix) derived from decellularized corneal extracellular matrix was fabricated. LC-COMatrix application to repair corneal stromal defects was evaluated ex-vivo and in vivo.

Methods : The LC-COMatrix was produced from porcine cornea by decellularization, digestion, and methacrylation. The in-situ cross-linking was achieved by combination of LC-COMatrix with a photo-initiating cocktail and curing with visible light (520 nm). The biodegradation, swelling behavior, viscosity, and rheological gelation kinetics of LC-COMatrix were studied. The adhesion-strength, burst-pressure (BP) following perforation repair, and tissue adhesiveness of LC-COMatrix were assessed ex-vivo using human corneas as substrate and compared to fibrin glue (FG) and 20% gelatin methacrylate (GelMA). The potential of LC-COMatrix to repair corneal stromal defects and full-thickness perforations was examined in a rabbit model.

Results : LC-COMatrix has proper swelling behavior, biodegradation, and viscosity for user-friendly corneal repair applications. The storage modulus of LC-COMatrix is 7.8±0.5kPA and is higher than FG (4.8±0.3kPa) and GelMA (5.1±3.2kPa). The adhesion-strength of LC-COMatrix is 21.8±2.3kPa which is significantly higher than that of GelMA (11.1±3.8kPa, p<0.0001) and FG (4.9±2.3 kPa, p<0.0001). The BP of a 2 mm perforation made by punch-biopsy and repaired with LC-COMatrix is 327±175 mmHg, while this value for GelMA is 151±48 mmHg (p=0.007) and for FG is 11±4 mmHg (p<0.0001). LC-COMatrix consistently repaired a human corneal stromal defect (10 mm diameter, 300 µm depth) and remained stable for 30 days with a smooth surface and comparable transparency to native human corneas. However, the FG degraded by day 15. In the corneal defects repaired with GelMA, the hydrogel shrank to the center of the corneal stromal defect during follow-up. Moreover, LC-COMatrix successfully integrated and repaired 3-mm lamellar defect in rabbit corneas which the epithelium regenerated, and the defect area remained transparent at 28 days follow-up. Additionally, the corneal macro-perforation (1-mm) in rabbit cornea was repaired with LC-COMatrix with healed epithelium and no subsequent leakage for 28 days.

Conclusions : LC-COMatrix is a natural ready-to-apply bio-integrating adhesive that is representative of the native corneal matrix with potential applications in corneal and ocular surgeries.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.