Associate professor Gudiseva Chandrasekher, left, and doctoral student Somshuvra Bhattacharya of South Dakota State University’s Department of Pharmaceutical Sciences view an image of the collagen architecture in a human cornea cross-section. They are using a patented biomaterial made from pig corneas to create a scaffold with which to fabricate a human corneal implant.
A patented biomaterial developed by South Dakota State University associate professor Gudiseva Chandrasekher has the potential to repair corneal damage and to create corneal implants. Chandrasekher been doing research on corneal tissue in the Department of Pharmaceutical Sciences since 2008.
This spring, he will begin a two-year research project through the Drug, Disease and Delivery Center to determine whether the patented biomaterial can be used to construct corneal implants. The SDSU-led 3D Center recently received a five-year, $3.9 million award from the South Dakota Research and Commercialization Council.
Corneal damage is the third-leading cause of blindness, according to a study in the 2016 Journal of the American Medication Association Ophthalmology that assessed the availability of corneal tissue worldwide. At that time, more than 12 million people worldwide were waiting for transplants. In 2020, the Eye Bank Association of America reported the number of cornea donors was down by 20% worldwide, but corneal transplants decreased by only 2.8%.
Researchers have also found that eye tissue, including the cornea, can harbor the virus that causes COVID-19, presenting a risk to transplant patients, according to an article in the 2020 EBAA Year in Review. In addition, corneas from patients who have had LASIK surgery cannot be used as transplants; therefore, the number of natural donors may be dwindling, Chandrasekher said.
“We want to use natural materials from different sources to make an implant that is as close to the natural cornea as possible,” he continued. This biomaterial will make corneal tissue more readily available and minimize the potential for rejection and other complications.
Healing power of corneal tissue
The cornea, which protects the pupil and iris and focuses light on the back of the eye, is more susceptible to damage than other ocular tissues. However, about 95% of the time the cornea can heal itself, Chandrasekher said. The cornea, which has three layers, is like skin in that the outer layer, known as the epithelium, routinely sheds and replaces cells so that it essentially regenerates every seven to 14 days.
Originally, Chandrasekher’s research focused on understanding the cellular mechanisms through which this wound healing occurs. The research was part of two centers—the 2010 Center for Research and Development of Light-Activated Materials, a collaboration among the University of South Dakota, SDSU and the Avera Research Institute, and the Translational Cancer Research Center, which involved the South Dakota State University and Sanford Research
“The cornea contains lots of collagens which have been shown to promote healing,” Chandrasekher said. However, when he asked a summer intern to extract collagens from pig corneas, the student adjusted the process and was able to completely dissolve the cornea, he recalled. “No one had done this before.” A patent for the biomaterial called liquid cornea extracellular matrix proteins, or ECMIX, was issued in 2020.
Because all of the natural materials were present in the liquified cornea, the next step was to culture the cells to see if they could create epithelial cells for wound healing. “No matter how we did it, the cells started growing,” he said.
The next summer, an undergraduate student and a graduate student worked on crosslinking the dissolved material, so it could possibly be used to treat keratoconus, a condition that causes the cornea to thin and eventually bulge, or as a film to protect a damaged cornea while it heals.
Using biomaterial for implants
Thus far, Chandrasekher has cultured cells of the outer epithelial and the middle stroma layers of the cornea on a cross-linked biomaterial scaffold. These scaffolds could be used as corneal implants. Next, he needs to tackle the innermost endothelial layer.
To take the research to the next level, he will work with South Dakota School of Mines assistant professor of nanoscience and engineering Scott Wood, whose expertise is in tissue engineering. Ophthalmologist Dr. Vance Thompson will provide guidance.
“We know the scaffold is good and grows the cells, but now comes fabrication of the scaffolding for a real cornea,” Chandrasekher said. “That is where the 3D (Drug, Disease and Delivery) center project will help.” A postdoctoral research associate, doctoral student and an undergraduate student will also work on the project at SDSU.
After the researchers have fabricated the corneas, they will do preclinical testing to both make sure the implants do not cause toxicity and determine their longevity.
Original Article: Biomaterial may help repair, replace damaged corneas
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