Bioengineered Cornea Can Restore Sight to the Blind and Visually Impaired

Researchers and entrepreneurs have created an implant that resembles the human cornea and is made of collagen protein from pig skin. In pilot research, 20 patients with damaged corneas—the majority of whom were blind before the implant—had their eyesight returned.

Nature Biotechnology has published the work jointly led by Linköping University (LiU) and LinkoCare Life Sciences AB.

The promising results offer a bioengineered implant as an alternative to the transplantation of donated human corneas, which are limited in nations where there is the highest demand for them, giving hope to those who suffer from corneal blindness and low eyesight.

“The results show that it is possible to develop a biomaterial that meets all the criteria for being used as human implants, which can be mass-produced and stored up to two years and thereby reach even more people with vision problems. This gets us around the problem of shortage of donated corneal tissue and access to other treatments for eye diseases”, says Neil Lagali, professor at the Department of Biomedical and Clinical Sciences at LiU, one of the researchers behind the study.

An estimated 12.7 million people around the world are blind due to their corneas, which is the outermost transparent layer of the eye, being damaged or diseased. They can only regain their vision by having a human donor's cornea implanted into them.

However, just one out of every 70 patients get a corneal transplant. Additionally, the majority of people in need of corneal transplants reside in low- and middle-income nations where access to medical care is extremely restricted.

“Safety and effectiveness of the bioengineered implants have been the core of our work, says Mehrdad Rafat, the researcher and entrepreneur behind the design and development of the implants. He is an adjunct associate professor (senior lecturer) at LiU’s Department of Biomedical Engineering and founder and CEO of the company LinkoCare Life Sciences AB, which manufactures the bioengineered corneas used in the study. 

“We’ve made significant efforts to ensure that our invention will be widely available and affordable by all and not just by the wealthy. That’s why this technology can be used in all parts of the world”, he says.

The cornea consists mainly of the protein collagen. The researchers employed collagen molecules from pig skin that were created under strict conditions for human use and that were extensively purified to create an alternative to human cornea. Since pig skin is a byproduct of the food business, it is convenient and cost-effective.

The loose collagen molecules were stabilized by the researchers as they built the implant, creating a strong, transparent material that could endure handling and implantation in the eye. While bioengineered corneas can be preserved for up to two years before use, donor corneas must be used within two weeks.

A brand-new, minimally invasive technique has also been devised by the researchers to treat the condition known as keratoconus, in which the cornea becomes so thin that it can result in blindness. The cornea of a keratoconus patient is now surgically removed at an advanced stage and replaced with a donated cornea that is stitched into place using surgical sutures. This type of invasive surgery is only performed at larger university hospitals.

“A less invasive method could be used in more hospitals, thereby helping more people. With our method, the surgeon doesn’t need to remove the patient’s own tissue. Instead, a small incision is made, through which the implant is inserted into the existing cornea”, says Neil Lagali, who has led the research group that has developed this surgical method. 

With this novel surgical technique, no stitches are required. A sophisticated laser can be used to make the corneal incision with extreme precision, but it can also be done manually using basic surgical tools when necessary. The procedure was initially tried on pigs and shown to be less complicated and potentially safer than a standard cornea transplant.

In Iran and India, two nations with high rates of corneal blindness and impaired eyesight but a dearth of donated corneas and available treatments, doctors used the surgical technique and implants. Twenty individuals who had advanced keratoconus and were either blind or in danger of losing their sight took part in the pilot clinical research and were given the biomaterial implant.

The surgeries went smoothly, the tissue recovered quickly, and an eight-week course of immunosuppressive eye drops was sufficient to prevent implant rejection. Traditional corneal transplants require medication to be taken for several years. No problems were observed throughout the two years that the patients were followed.

The pilot clinical study's main goal was to determine whether using the implant was safe. However, the results of the implant startled the researchers. Both the thickness and curvature of the cornea were restored to normal. The patients' sight improved collectively to the same extent as it would have following a corneal transplant using donor tissue.

Before the operation, 14 of the 20 participants were blind. After two years, none of them was blind anymore. Following surgery, three of the Indian volunteers who had been blind before the trial had perfect (20/20) eyesight.

Before the implant can be used in healthcare, a larger clinical trial and regulatory authority market approval are required. Additionally, the researchers aim to investigate whether the technology can be applied to the treatment of additional eye conditions and whether the implant can be personalized for even higher efficacy.

LinkoCare Life Sciences AB, which is responsible for the production, certification, packaging, and sterilization of the implants used in the study, with the support of Care Group India, covered the cost of implant manufacturing, ISO-compliant preclinical testing, and clinical testing.

The European Union's Horizon 2020 Programme, as well as ALF grants from Linköping University and the stergötland Region, provided further support for the investigation of biomaterials and surgical creation and testing. These funders were not involved in the planning or carrying out of the study. The patent is owned by LinkoCare AB, whose board member is Mehrdad Rafat. Shideh Tabe, another research co-author, is a member of the corporation's board of directors.