Abstract
Purpose :
The cornea is the dome-shaped and transparent outermost part of the eye that focuses light onto and protects intraocular neurosensory structures. A diseased cornea can quickly lead to scarring, thinning, and blindness. Patients with corneal blindness are currently treated with corneal transplantation from cadaveric donors. However, less than 2% worldwide can be treated by corneal transplantation due to a lack of donor tissue. Hence, tissue engineering to replace donor corneas can meet a major global public health need. The ideal biomaterials for cornea replacement should be biocompatible, transparent, mechanically stable, promote corneal epithelial cell growth and stromal regeneration, and be degradable in a way that promotes tissue regeneration and bio-integration.
Methods :
Collagen is a major component of corneal stroma and is cell-adhesive. Hyaluronate is known to promote corneal epithelial wound healing and has been used in eye drops and intraocular surgery. We used a bio-orthogonal strain-promoted azide-alkyne cycloaddition reaction to crosslink collagen and hyaluronic acid to each other. The collagen is modified with dibenzocyclooctyne and the hyaluronate is modified with azide and a fluorophore. The modified hyaluronate and collagen are added to the corneal wound respectively and mixed on the corneas of rabbits under ambient conditions without a catalyst or light activation. A contact lens and tarsorrhaphy are then applied. The curvature of the treated cornea is monitored by OCT and photography. After seven days, the cornea is fixed, and immunofluorescence staining is performed to evaluate the biological response to the gel.
Results :
The co-polymeric hydrogel formed in situ at the corneal wound site under ambient conditions without a catalyst or light energy. No ocular inflammation or damage was found in the surrounding tissue. The hydrogel maintained the curvature of the wounded cornea for 7 days in the rabbit. Immunofluorescence staining showed that the hydrogel supported the growth of corneal epithelial cells on its surface.
Conclusions :
Here, we developed collagen and hyaluronate-based copolymer which can form a transparent gel in the wound of the cornea in situ without the need for an external catalyst or trigger such as light. Future studies will focus on the therapeutic potential for vision restoration in animal models.
This is a 2020 ARVO Annual Meeting abstract.