Biomedical engineers are developing a number of techniques to 3D print corneal transplants to overcome shortages of donated corneas.
Bioengineers around the world are devising various methods of making different kinds of corneal transplants, aimed to treat a gamut of debilitating eye diseases.
Cornea, the eye's protective outer layer, serves as a barrier against dirt, germs, and other damaging agents. It is a complex organ that consists of several layers: the epithelial layer, the Bowman's layer, the corneal stroma, the Descemet's membrane, and the inner corneal endothelium made of endothelial cells. Different eye diseases affect different layers, hence different solutions are necessary for each layer.
Cornea can be easily damaged by infection, an injury by a sharp or blunt object, and even by contact lenses. The resulting scars can affect vision, and block or distort light as it enters the eye. The World Health Organization estimates that worldwide about 4.9 million people suffer from blindness due to corneal scarring.
Certain diseases such as Fuchs’ dystrophy, caused by endothelial cells’ death, can damage cornea as well. Normally, the endothelial cells maintain a healthy balance of fluids within cornea, but when they die out, fluids accumulate and cause swelling, which interferes with vision.
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The only option to restore vision in patients with a severely impaired corneal endothelial layer is a donated transplant.
There are 40,000 to 50,000 corneal transplants performed in the U.S. each year, with about half of them replacing the damaged endothelium layer, whether due to Fuchs dystrophy or other causes. These transplants are received through eye banks and patients often have to wait a long time for them.
“Generally, there is a big shortage of corneas,” said Lior Shav of Precise Bio, a North Carolina-based biotechnology company working on creating endothelial implants. “There’s about one donor for every 70 people that need that cornea.”
To solve this problem, scientists at Precise Bio devised a novel way of culturing and 3D printing corneal endothelial cells. While their method still relies on corneas donated to eye banks, it would allow producing about 70 transplants from only one donated cornea—to match the existing demand.
At the company’s facilities, cells from donor corneas are first cultivated to generate more cells, and then 3D printed into functional implants.
To produce a living tissue, corneal cells are 3D printed together with a supporting bioink—an extracellular matrix (ECM)—the structural material comprised of collagen and other vital compounds that support all body tissues.
“To be viable, cells must feel comfortable in their environment, otherwise they don't proliferate or adhere to each other,” Aryeh Batt, the company’s co-founder, explained. The ECM bioink provides that nurturing media.
“So when a drop comes out of the printer it comes out together with the cell and with the material that structures the tissue,” he said. “This way we can maintain the properties and viability of the cells throughout the process.”
Lastly, the cells undergo a maturing process at body temperature, fusing into a viable implant, with a quality similar to that of a human cornea at birth.
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Other research teams are also experimenting with corneal transplants. Earlier this year, bioengineers from Newcastle University in the U.K. 3D printed a corneal stroma equivalent, matching the naturally curved corneal shape.
The team also used a printable bioink solution fashioned from donor cells and the necessary supporting compounds such as alginate and collagen. Their method yields a material stiff enough to hold its shape but soft enough to squeeze through the nozzle of a 3D printer—during which the cells are kept alive thanks to the bioink. The mixture is printed according to a preset pattern generated by a computer, and it takes about 10 minutes to 3D print the cornea-shaped implant.
That curved shape is essential, said Che Connon, professor of tissue engineering at Newcastle University.
“Curvature is an important aspect of cornea,” Connon said. “We regard it as a critical part of a functional tissue to have that curvature.”
He added that the realm of corneal implants is a rapidly developing field, in which multiple teams are experimenting with different approaches and are at different stages of progress. For instance, Precise Bio engineers have experimented with transplanting corneal grafts in animals, but their results have not been published yet.
Human trials have not commenced, but researchers are hoping that once implanted, the transplants will serve patients for a long time. “I can’t tell definitively because we haven’t done that yet,” Connon said. “But we hope they will last for years.”
Lina Zeldovich is an independent writer.
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