Designing hydrogel adhesives for corneal wound repair

Abstract

Today, corneal wounds are repaired using nylon sutures. Yet there are a number of complications associated with suturing the cornea, and thus there is interest in an adhesive to replace or supplement sutures in the repair of corneal wounds. We are designing and evaluating corneal adhesives prepared from dendrimers--single molecular weight and highly branched polymers. We have explored two strategies to form these ocular adhesives. The first involves a photocrosslinking reaction and the second uses a peptide ligation reaction to couple the individual dendrimers together to form the adhesive. These adhesives were successfully used to repair corneal perforations, close the flap produced in a LASIK procedure, and secure a corneal transplant.

Figure 1

Schematic of a linear (A) and dendrimer (B) polymer. The three main structural zones of the dendrimer consisting of the central core, internal branching layers, and peripheral groups are labeled.

Figure 2

Divergent synthesis of a generation three dendimer showing the step-wise coupling and deprotection reactions. The monomer consists of three parts – the portion for coupling to a growing dendrimer, a portion which has two potential coupling sites which is capped by a protecting group. After the monomer is coupled, the protecting group is removed, and the monomer is added again to create the large dendrimer. This process is repeated until a specific dendrimer generation is prepared.

Figure 3

Chemical structures of a generation 4 poly( ) dendrimer ([G4]-P -OH), a generation 3 dendritic-linear copolymer (([G3]-P -OH)₂- ), and a generation 2 lysine-cysteine dendron ([G2]- ).

Figure 4

Schematic of the two crosslinking strategies: (top) photocrosslinking reaction and (bottom) nucleophile-electrophile reaction.

Figure 5

Photographs of the closure procedure for a 4.1 mm full thickness corneal laceration. (left) Placement of the adhesive solution on the wound. (middle) Photocrosslinking of the solution to form the adhesive. (right) Sealed corneal laceration.

Figure 6

Seidel test confirming the closed corneal laceration.

Figure 7

H & E stains of the repair chicken cornea after treatment with a dendrimer adhesive (top) and suture (bottom).

Figure 8

(top) A 3 mm clear corneal wound leaking before closure. (bottom) A sealed wound with the dendritic adhesive composed of ([G2]- and -DA.