A biomimetic hydrogel-based therapeutic approach for preventing corneal scarring

Abstract

Purpose : Corneal wounding, due to infection, injury or inflammation, heals by stromal scarring and opacification. There is an unmet clinical need for a biomaterial that can prevent the development of corneal stromal scar or as therapeutics to treat these scars. This study reports the possible prophylactic potential of biomimetic hydrogels derived from non-transplant grade human cadaveric and bovine corneas.

Methods : Human (h) and Bovine (b) cornea were decellularized using 1.5M NaCl solution to prepare decellularized corneal extracellular matrix hydrogel (DCMH). In-vitro characterization of retained DNA, sulfated glycosaminoglycans (sGAG) and collagen of native tissue and hDCMH, bDCMH were evaluated. Physical, Chemical and environmental stability of the DCMH was looked into for viscosity profile, shear recovery and gelation property. In-vivo investigation for a scar-free cornea regeneration was conducted by corneal injury model in New Zealand white rabbits (n=6) removal of 200µm depth and 3mm diameter of stromal tissue. DCMH from both sources were topically applied to treat the surgically induced cornea wounds in rabbits, followed by clinical evaluation and comparison with collagen and sham controls. Statistical analyses were performed using ANOVA and Student's t-test.

Results : The total dsDNA, sGAGs and collagen content retained was found to be 2.07 ± 0.23% and 2.12 ± 0.51%; 73.35 ± 7.05% and 66.47 ± 4.01%; 66.47 ± 4.01% and 50.57 ± 4.73% respectively in hDCMH and bDCMH. Viscosity recovered after shear thinning was 307100 mPa.s and 281600 mPa.s for hDCMH and bDCMH. In the in vivo study, the average epithelial thickness recovered was 103.5 ± 12.3 % in the collagen group, 95 ± 11.44% in hDCMH, and 81.95 ± 15.8% for the sham group, significant between collagen and sham control. The central corneal thickness (CCT) regained was 88.85 ± 4.08% collagen group, 78.39 ± 5.059% sham control, 97.07 ± 1.59% hDCMH, 96.52 ± 0.12 % bDCMH with significant difference between hDCMH and bDCMH group.

Conclusions : Our DCMH promotes early re-epithelialization, stromal regeneration, and transparency, indistinguishable from a healthy cornea. These findings suggest that the application of our formulated decellularized corneal matrix hydrogel could be a new promising approach as a minimally invasive and easily performable procedure to prevent scarring followed by traumatic injuries in the cornea.

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