Abstract
Purpose :
Corneal tissue engineering is effective in treating corneal defects and restoring the vision of millions worldwide. In situ-forming gels are advanced because they avoid complex surgical procedures and adverse events. We have previously developed 2 bio-orthogonal in situ-forming hydrogels, which enhanced corneal wound healing in ex vivo and 1-week in vivo studies: a collagen-only gel (Col) 1 and collagen-hyaluronan gel (HA-Col) 2, both crosslinked via strain-promoted azide-alkyne cycloaddition reaction (SPAAC). Here we compared the long-term performance of the two gels on corneal wound healing in rabbits. We studied the impact of using SPAAC versus UV-based photocrosslinking in terms of their effects on corneal wound healing. Our purpose is to identify the best gel components and crosslinking chemistry to make translatable in situ-forming hydrogels for corneal wound healing in human patients.
Methods :
The Col and HA-Col gels were synthesized following our previous protocol.1, 2 The UV-crosslinked collagen-hyaluronan gel (HA-Col UV) shares the same polymer contents with the HA-Col but differs in the crosslinking chemistry. The H-C UV gel was formed by exposing a mixture of HA-methacrylate and collagen-methacrylate using LAP as a photoinitiator. Anterior lamellar keratectomies were performed in the corneas of rabbits followed by adding freshly made gels.
Results :
No ocular inflammation or damage was found in the surrounding epithelial, stromal, and endothelium in the eyes treated with the bio-orthogonal Col and HA-Col gels, while inflammation, corneal edema, and corneal neovascularization were observed in the eyes treated with the UV-crosslinked gel counterparts. The epithelium was completely healed within 30 days for the control (untreated) and bio-orthogonally gels treated groups, while epitheliopathy was still noted after 2 months in the UV-crosslinked gel-treated eyes. The HA-Col gel exhibited significantly faster re-epithelialization at 1 week than the other gels. At 2 months, the HA-Col gel-treated corneas exhibited significantly greater transparency and improved restoration of corneal curvature.
Conclusions :
In summary, SPAAC-crosslinked HA-Col facilitated superior corneal wound healing than SPAAC-crosslinked Col and UV-crosslinked HA-Col gels. Further preclinical work is merited on studying the therapeutic potential for the treatment of corneal injuries and scars.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.