No abstract

Visually significant corneal injuries and subsequent scarring collectively represent a major global human health challenge, affecting millions of people worldwide. Unfortunately, less than 2% of patients who could benefit from a sight-restoring corneal transplant have access to cadaveric donor corneal tissue. Thus, there is a critical need for new ways to repair corneal defects that drive proper epithelialization and stromal remodeling of the wounded area without the need for cadeveric donor corneas. Emerging therapies to replace the need for donor corneas include pre-formed biosynthetic buttons and in situ-forming matrices that strive to achieve the transparency, biocompatibility, patient comfort, and biointegration that is possible with native tissue. Herein, we report on the development of an in situ-forming hydrogel of collagen type I crosslinked via multi-functional polyethylene glycol (PEG)-N-hydroxysuccinimide (NHS) and characterize its biophysical properties and regenerative capacity both in vitro and in vivo. The hydrogels form under ambient conditions within minutes upon mixing without the need for an external catalyst or trigger such as light or heat, and their transparency, degradability, and stiffness are modulated as a function of number of PEG arms and concentration of PEG. In addition, in situ-forming PEG-collagen hydrogels support the migration and proliferation of corneal epithelial and stromal cells on their surface. In vivo studies in which the hydrogels were formed in situ over stromal keratectomy wounds without sutures showed that they supported multi-layered surface epithelialization. Overall, the in situ forming PEG-collagen hydrogels exhibited physical and biological properties desirable for a corneal stromal defect wound repair matrix that could be applied without the need for sutures or an external trigger such as a catalyst or light energy.

Timely treatment of corneal injuries injury can help to prevent corneal scarring, blindness, and the need for corneal transplantation. This work describes a novel hydrogel that can fill corneal defects and assist in corneal regeneration. This hydrogel is a simultaneous interpenetrating polymer network (IPN) composed of collagen cross-linked via strain-promoted azide−alkyne cycloaddition reaction and hyaluronic acid cross-linked via thiol−ene Michael click reaction. The formation of the IPN gel was confirmed via FTIR spectra, UV−vis spectra, and morphological changes. We compared the gelation time, mechanical properties, transmittance, and refractive index of the IPN gel to the collagen gel, hyaluronic acid gel, and semi-IPN gel. The IPN combined the advantages of collagen and hyaluronic acid gels and supported corneal epithelial cell growth on its surface. When applied to corneal stromal defects in vivo, the IPN avoided epithelial hyperplasia, decreased stromal myofibroblast formation, and increased tight junction formation in the regenerated epithelium.