Professor Develops Artificial Cornea Grown on a Chip
By: Amanda Bowman
Technological medical advancements have enhanced our way of life in unprecedented ways, from leadless pacemakers to gene therapy treatments. Such breakthroughs continue to happen, thanks to professors in the Texas Tech University System.
Jungkyu (Jay) Kim, an assistant professor in the Department of Mechanical Engineering in the Edward E. Whitacre Jr. College of Engineering at Texas Tech University and an adjunct professor in the School of Medicine at Texas Tech University Health Sciences Center (TTUHSC), collaborated with Dr. Ted Reid, a professor in the Department of Ophthalmology & Visual Sciences in the School of Medicine, to develop an artificial, human cornea-on-a-chip. The findings were recently published in the Royal Society of Chemistry's scientific journal, "Lab on a Chip."
The cornea-on-a-chip helps determine how much medication is getting through to the eye. Currently, the most common way to test this is to use rabbit eyes. The developers hope this new chip will reduce the use of animal testing for eye medication.
"Nobody knows how much eye medicine is really released into the eye because of certain barriers," Kim said. "The first barrier is the cornea. The cornea itself is made up of five layers of cells. Companies usually use rabbit eyes because of structural similarity with slow blinking speed. However, the outcome of drug test won't be the same with that of human cornea. To estimate pharmacokinetics of ocular drugs precisely, we try to replicate the human cornea structures instead of extracting eyes from animals."
This isn't the first eye-on-a-chip produced, but it is one of a kind because the chip developed by Kim provides the required tear flow associated with blinking patterns of an eye, a vital component missing from previous chips.
"There are some previously developed tools, but their problem is they just use a static well," Kim said. "What people who test these medications do is dissect the cornea, put it on a slide, drop the drug on top and let it sit for a while to see how much medication was released through the layers. The problem is, when you drop medicine in your eyes, tears form. If tears get in, a drug will dilute at certain levels. Tears get in because a facial muscle is pressurized on the lacrimal gland which causes us to blink. So, we incorporated the blinking speed to see how much drug is diluted and how much drug is really available on the top and bottom layers of the cornea."
Eliminating a step in the development of a drug could mean major cost savings, which potentially could trickle down to consumers.
"The overall drug-development process is a billion-dollar business," Kim said. "If you eliminate one step, then you could save millions of dollars, potentially a billion dollars. They can now test first with a chip and save money by getting rid of something that's not working. Also, that decreases the drug cost at the end."
How it's made
The chip itself is a microfabricated polymer microchip similar to the structure of human cornea and can be created in a few hours. Kim uses an additive biomanufacturing process that helps the cellular layers of the cornea stack on top of one another, forming a multilayer cell instead of growing in different directions.
"Culturing the cell inside the chip takes longer than we thought," Kim said. "It's almost impossible to wait for five layers of cells to grow. You need about a month to grow a miniscule amount, and nutrients are limited. If you wait and you stack them, the middle layer cells always need more nutrients because the top and bottom layers take all the nutrients. This is the reason why we use an additive biomanufacturing process. We inject the cells into the channel on the chip, let them grow and repeat. It's a much faster multilayer process."
Dr. Reid and his team provided the cells Kim needed to complete the chip.
"They're real cells," Kim said. "It's cornea epithelial cells; immortalized cells that are really useful for testing those kinds of structure analysis."
Some people may think of immortalized cells in the sense of cancer, where certain cells continue to divide at a rapid, unchecked rate. However, these immortalized cells are the kind anyone would want.
"Immortalized means these cells maintain their phenotype, or observable traits," Kim said. "It makes them easy to deal with during testing. If you have a cell switching its phenotype quickly, then it's really hard to work with."
Regenerative wound healing
Though Kim mainly started this research to help improve and speed up the drug development evaluation process for eye medication, there is another area he'd like to explore: regenerative wound healing.
"Wound healing is unique on the cornea because you can scrape it many times, but it's OK," Kim said. "The first layer of the cornea can be removed by quickly rubbing your finger over your eyes. After a day or two, everything is fine and normal. How come?"
The reason for this incredible regenerative power is the eye's corneal epithelial cell at the basal layer of the limbus.
"Limbal corneal epithelial cells have stem cell-like wound-healing properties that is a really unique feature of the eyeball," Kim said. "Other parts of your body have some healing process, but not as quickly as the eye. We're trying to figure out the spatial temporal analysis, the timeline, of how fast these cells move around on the eye."
Even though the eye has incredible self-healing properties, it's not immune to infections. Anyone with a child knows conjunctivitis, or pink eye, can wreak havoc. According to Kim, the corneal epithelial junction is one of the strongest barriers in the body, which makes drug penetration so difficult. So how can bacteria get in seemingly so easily?
"That process is really unknown," Kim said. "Somehow, the bacteria dissolve junction proteins by releasing toxic materials. We can inoculate the bacteria and see how fast they swim into and break up these junctions. After they penetrate through, our immune system is picked up and that's why you see the red eyes, because blood starts getting to it. So, we also can use the chip to study that process."