Injectable, in situ crosslinked hydrogels by Fenton’s Reagent (Fe (II) & H2O2) for corneal perforations

Abstract: Corneal perforations are medical emergencies in which the cornea is partially or completely ruptured, resulting in the loss of stability of the whole eye. Such situations can be caused by bacterial or fungal keratitis, autoimmune, or ocular-surface related disorders. Corneal perforations, if left untreated, can cause partial or total blindness. Therefore, immediate treatment is necessary. The best treatment available is corneal transplantation; however, due to donor limitation, this treatment is non-feasible. Alternatively, applying cyanoacrylate or fibrin glue is the treatment used clinically. Nonetheless, these treatments have been shown to cause inflammation and result in recurrence of the perforation which may lead to a full thickness donor transplantation in future. Thus, an easily available and applicable, biological and non-immunologic solution is required for a better treatment. For this, injection of in situ crosslinked and biocompatible hydrogels can provide a better long-term solution. Even though there are several different strategies for crosslinking of hydrogels such as chemical crosslinking, enzyme mediated, or UV-initiated crosslinking, there are several limitations in these methods such as cytotoxicity or immunogenic potential of the method. This study involves the development of injectable in situ forming gel crosslinked by Fenton´s reaction, a chemical mimic of horseradish peroxidase (HRP), which can have potential applications for corneal perforations. The polymers used in this study were both synthetic polymers such as poly (ethylene glycol) (PEG) and ECM-derived such as gelatin.The results demonstrated that it is possible to tune the mechanical properties and gelling kinetics of the resulting hydrogel by adjusting the reactant compositions. In vitro cytotoxicity tests were performed for relevant concentrations of Fe (II) and hydrogen peroxide, and have shown that the cells remained viable.