Repair of wounds after traumatic or surgical injury is of significant clinical and research importance. The cornea of the eye is one such site where tissue remodeling after injury is critical since the cornea serves an important role in refracting and focusing light rays necessary for clear vision. The cornea possesses the unique characteristics of an orderly arrangement of stromal collagen fibrils and a lack of blood vessels that result in transparency. Inadequate healing of the cornea after injury can result in decreased or loss of vision. We have designed, synthesized, and evaluated new dendritic polymer-based hydrogel sealants for the repair of corneal wounds.
Hydrogel-based tissue adhesives are attractive materials for sealing corneal wounds compared to sutures since hydrogels can not only close the injury but also serve as a temporary scaffold until new corneal tissue remodels the wound. The current surgical practice of using monofilament nylon sutures inflicts additional trauma to the wound and can be associated with a number of post-operative complications including microbial keratitis, extended healing time and astigmatism.
Crosslinking of these dendritic macromolecules affords the hydrogel adhesives. The crosslinked hydrogel adhesives are transparent, pliable, and soft. Hydrogel networks can be formed using two strategies (see Figure). In the first approach, the end groups of the dendritic macromolecule are modified to contain an acrylate or other free-radical polymerization group which is subsequently corsslinked using light. The second approach relies on multiple chemical ligation reactions between the macromers to form the hydrogel adhesive. This chemical ligation crosslinking strategy for hydrogel formation is favorable since it is a mild reaction that can be performed in aqueous solution (pH 7.4 and 37 oC) in the presence of functional groups, and it does not generate any side-reaction products.
The adhesives based on a photocrosslinkable ABA dendritic-linear copolymer composed of glycerol, succinic acid, and polyethylene glycol have been successfuly used to seal ex vivo and in vivo full-thickness corneal lacerations, secure ex vivo laser in-situ keratomileusis (LASIK) flaps, and close ex vivo corneal transplants. The second type of adhesive developed, that self-gels upon mixing of a peptide dendron and a PEG dialdehyde, has been successfuly used to seal ex vivo cataract incisions, to repair ex vivo corneal lacerations, and to secure ex vivo corneal transplants using a reduced number of sutures.