>Significance: Hyaluronic acid (HA, or hyaluronan) is a ubiquitous naturally occurring polysaccharide that plays a role in virtually all tissues in vertebrate organisms. HA-based hydrogels have wound-healing properties, support cell delivery, and can deliver drugs locally.>Recent Advances: A few HA hydrogels can be customized for composition, physical form, and biomechanical properties. No clinically approved HA hydrogel allows for in vivo crosslinking on administration, has a tunable gelation time to meet wound-healing needs, or enables drug delivery. Recently, a thiolated carboxymethyl HA (CMHA-S) was developed to produce crosslinked hydrogels, sponges, and thin films. CMHA-S can be crosslinked with a thiol-reactive crosslinker or by oxidative disulfide bond formation to form hydrogels. By controlled crosslinking, the shape and form of this material can be manipulated. These hydrogels can be subsequently lyophilized to form sponges or air-dried to form thin films. CMHA-S films, liquids, and gels have been shown to be effective in vivo for treating various injuries and wounds in the eye in veterinary use, and are in clinical development for human use.>Critical Issues: Better clinical therapies are needed to treat ophthalmic injuries. Corneal wounds can be treated using this HA-based crosslinked hydrogel. CMHA-S biomaterials can help heal ocular surface defects, can be formed into a film to deliver drugs for local ocular drug delivery, and could deliver autologous limbal stem cells to treat extreme ocular surface damage associated with limbal stem cell deficiencies.>Future Directions: This CMHA-S hydrogel increases the options that could be available for improved ocular wound care, healing, and regenerative medicine.
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