An Injectable, Shape-Retaining Collagen Hydrogel Cross-linked Using Thiol-Maleimide Click Chemistry for Sealing Corneal Perforations

Injectable hydrogels show great promise in developingnovel regenerativemedicine solutions and present advantages for minimally invasive applications.Hydrogels based on extracellular matrix components, such as collagen,have the benefits of cell adhesiveness, biocompatibility, and degradabilityby enzymes. However, to date, reported collagen hydrogels possesssevere shortcomings, such as nonbiocompatible cross-linking chemistry,significant swelling, limited range of mechanical properties, or gelationkinetics unsuitable for in vivo injection. To solvethese issues, we report the design and characterization of an injectablecollagen hydrogel based on covalently modified acetyl thiol collagencross-linked using thiol-maleimide click chemistry. The hydrogel isinjectable for up to 72 h after preparation, shows no noticeable swelling,is transparent, can be molded in situ, and retainsits shape in solution for at least one year. Notably, the hydrogelmechanical properties can be fine-tuned by simply adjusting the reactantstoichiometries, which to date was only reported for synthetic polymerhydrogels. The biocompatibility of the hydrogel is demonstrated in vitro using human corneal epithelial cells, which maintainviability and proliferation on the hydrogels for at least seven days.Furthermore, the developed hydrogel showed an adhesion strength onsoft tissues similar to fibrin glue. Additionally, the developed hydrogelcan be used as a sealant for repairing corneal perforations and canpotentially alleviate the off-label use of cyanoacrylate tissue adhesivefor repairing corneal perforations. Taken together, these characteristicsshow the potential of the thiol collagen hydrogel for future use asa prefabricated implant, injectable filler, or as sealant for cornealrepair and regeneration.