Biomedicine

Artificial Cornea Mimics Natural Counterpart

A new material could increase the availability of corneal transplants.

Millions of people around the world are blind due to corneal disease or damage. In hopes of making corneal transplants more widely available, researchers have designed an artificial cornea made from a water-filled polymer that closely resembles the eye’s natural cornea. Compared with existing commercially available artificial corneas, the new implant could reduce the likelihood of infection and other complications that arise from surgery.

Seeing clearly: This hydrogel-based artificial cornea developed by researchers at Stanford University contains microscopic pores that were patterned using photolithography. Once implanted in a patient, cells migrate through the pores and help integrate the artificial cornea with the surrounding tissue.

Approximately 40,000 patients undergo corneal transplant surgery in the United States every year. The vast majority of these people receive a replacement cornea from a human donor. Although the surgery has a high success rate, the supply of donor tissue is limited, and wait lists can be long. In the developing world, access to donor tissue is even more difficult. And yet “most cases of corneal blindness are in developing countries,” says Tueng Shen, an expert in cornea and refractive surgery at the University of Washington Medical Center, in Seattle.

To overcome this problem, researchers have been developing artificial corneas using synthetic materials. The most successful of these to date is the Dolhman-Doane keratoprosthesis, which received approval from the U.S. Food and Drug Administration in 1992 and has been used in hundreds of patients. It consists of a hard, clear plastic core surrounded by human donor tissue to help attach the cornea to the eye.

However, because the implant is prone to infection and other complications, patients must take a lifelong course of antibiotics. As a result, the artificial cornea is used only as a last resort in patients who have repeatedly rejected natural donor tissue or who are otherwise not eligible for such transplant surgery.

Instead of using hard plastic, Stanford University chemical engineer Curtis Frank and former graduate student David Myung have created an artificial cornea based on a soft hydrogel. The water-swollen gel is made of a mesh of two polymer networks. The first network is made of polyethylene glycol, the second of polyacrylic acid. “It’s like filling up the holes in the sponge with a second material,” says Frank. “You can’t separate one from the other. They become inextricably intertwined.”

The resulting clear material is mechanically robust, despite being 80 percent water. The high water content, explains Stanford ophthalmologist Christopher Ta, is critical for allowing glucose and other nutrients to diffuse through the cornea and encourage the growth of epithelial cells on the implant’s surface. “We think this is important for minimizing risk of infection,” says Ta. “In the natural cornea, the epithelial layer is very important for protection.”

For instance, one type of artificial cornea currently marketed under the name AlphaCor is also based on a hydrogel. Yet the material contains only half the amount of water as the Stanford implant. As a result, it can’t support the growth of epithelial cells, which many researchers say could explain AlphaCor’s high failure rate.

Because the Stanford hydrogel is inert, cells don’t normally stick to it. So, with the help of Stanford bioengineer Jennifer Cochran, the researchers devised a way of tethering collagen to the artificial cornea’s surface. The collagen, in turn, binds to the epithelial cells. Cochran is working on incorporating growth factors and other components of the cell’s natural environment into the material.

Using photolithography, Frank’s team can also create patterns of microscopic pores around the edges of the implant. That way, he says, when the cornea is implanted in the patient’s eye, cells will migrate through the pores, anchor the cornea, and help integrate the material with the native tissue. This will also reduce the number of sutures required to keep the artificial cornea in place, says Frank.

Shen, who was not involved in the Stanford effort, says that the development of new artificial corneas will be important for solving a critical health problem. However, she wonders whether the design of these new implants is well suited for use in the developing world. For instance, hydrogel-based implants might require relatively complicated surgery. “That could be difficult in terms of training surgeons abroad,” Shen says. She is also concerned about the potentially high cost of the materials, whether they can be applied to large populations, and whether they will require a lot of follow-up care.

So far, the Stanford group has shown that the diffusion of glucose across the material is equal to that of the human cornea, and preliminary studies in rabbits show that implants can support the growth of epithelial cells. The researchers say that studies in human patients are still several years away.

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