By introducing just the right biocompatible molecules to one another, a research team led by Mark Grinstaff, an associate professor of biomedical engineering and of chemistry at Boston University, has produced an elastic, transparent gel that sets so fast and adheres so surely to the eye’s surface that it could soon become the first and best choice for sealing corneal incisions.
The substance, known as a hydrogel, promises to be a useful tool in the kit used for the most common of ophthalmic surgeries: cataract removal. Currently, 11 million such surgeries are performed worldwide annually, a figure expected to increase as the world’s population grows older.
A cataract is a clouding of the eye’s lens, a condition that obscures vision by gradually blocking the light that enters the eye. To remove a clouded lens, a surgeon makes a small incision in the conjunctiva, the margin between white area (tunica) and the clear area (cornea) of the outer eye. Through this tiny opening, the surgeon works to break up the lens, often by using high-frequency sound waves; extracts the destroyed lens; then implants a synthetic lens. Currently, the procedure finishes with the surgeon following one of two accepted paths: allowing the incision to seal itself or stitching the incision shut using nylon sutures.
Each closing method has its drawbacks. Self-sealing, in which the open wound closes gradually over time, carries the risk of infection as well as leakage of intraocular fluid. Suturing likewise can carry the risk of infection and inflammation, as well as the abnormal development of blood vessels, a condition known as vascularization.
To potentially stave off these post-operative complications, Grinstaff’s team decided to build a biological bandage using versatile materials known as dendritic macromolecules. Capable of extensive molecule-to-molecule linking, these polymer complexes can be designed to meet very precise specifications, making them ideal substances for medical applications.
By controlling chemical composition, structure, and molecular weight of the molecules that make-up dendritic macromolecules, researchers can produce structures with surface functions that facilitate surface adhesion or biological recognition. When used to formulate hydrogels, these macromolecules show several advantages, including the capacity to cross-link well at low concentrations and to form low viscous solutions that can be injected into irregularly shaped sites. The solutions can then “cure” to fill the designated space.
Grinstaff and colleagues built their hydrogels from a biocompatible peptide dendritic macromolecule and poly(ethylene glycol) (PEG). When solutions of the two components were mixed together, the cysteine residues of the dendritic macromolecule quickly linked up with the PEG molecules to form the hydrogel.
Working with research collaborator Terry Kim, an associate professor in the Department of Ophthalmology at Duke University Medical Center, the researchers applied the hydrogel to corneal incisions made in enucleated eyeballs. The gel sealed the incision in a few minutes, less than the time needed for suturing. The hydrogel also developed a seal that was hard to breach, refusing to leak intraocular fluids at pressures approximately 12 times greater than those in the normal human eye (184 ± 79 millimeters of mercury [mmHg] and 12 – 16 mmHg, respectively). Incisions that had been left alone or that had been sutured withstood pressures approximately two times (24 ± 8 mmHg) and four times (54 ± 16 mmHg) greater, respectively, than those in the normal human eye.
The team speculates that the physical barrier that the hydrogel forms on the eye will help prevent infection and that the ease with which the hydrogel is applied will inflict less trauma to the eye, especially when compared with suturing. The team noted, too, that the gels are transparent and have a refractive index similar to that of the human cornea (thus it will not interfere with light reaching the retina), both solid pluses for repairing incisions to the outer eye.
“We are excited about these results,” says Grinstaff, “since there is significant clinical interest for an alternative to sutures in the repair of ophthalmic wounds created during surgical procedures, trauma, or disease.”
The team’s findings will appear in the October 13 issue of the Journal of the American Chemical Society.