Young Innovators Award to Miguel González-Andrades from the Biosanitary Research Institute of Granada

Miguel González-Andrades, 29 years old and belonging to the Grupo Ingeniería Tisular del ibs.GRANADA receives the Innovators Under 35 Award for having created artificial human corneas to treat severe vision problems. 

Is it possible to manufacture artificial tissues that integrate into the human body without rejection? Thanks to the great advances of the last decades in tissue engineering, the answer is yes. However, on a daily basis, there are still very few tissues of this type in the service of the surgeon. The best known, artificial skin, is used in the treatment of people who have suffered serious burns, but what if the damage has occurred in a biological structure as delicate as the human cornea?

Until now, the alternatives for patients suffering from vision loss due to severe corneal diseases are scarce, in some cases non-existent. In the coming years, thanks to the work of the young innovator Miguel González-Andrades, medicine may finally be able to offer you an answer.

This 29-year-old researcher and ophthalmologist has designed together with his team at the Tissue Engineering Group of the ibs.GRANADA several models of artificial human corneas based on biodegradable materials that could be used to treat problems such as corneal blindness, a pathology that affects 28 million people in the world. The most advanced of these models has already been tested in vitro and in vivo with good results. In addition, the team led by González-Andrades began a multicenter trial in humans in February this year to demonstrate its safety and good integration in the recipient eye.

Currently, the most common way to treat corneal blindness is through an allogeneic transplant (performed using a cornea from a donor) and through the implantation of so-called keratoprostheses (non-biological artificial corneas). Regarding the former, donors are scarce, and will become increasingly so given the growing popularity of surgeries to correct defects such as myopia, in which the corneas of those who undergo them are rendered unusable for transplantation. Keratoprostheses, on the other hand, have several disadvantages: they are expensive and carry a high risk of complications, requiring lifelong medical treatment and follow-up. "They are usually used as a last resort in patients who have rejected human donor corneal tissue," explains González-Andrades, who, in view of these drawbacks, emphasizes the "undeniable need to develop optimal human artificial corneas."

Despite this urgency, only one comprehensive trial of biosynthetic artificial corneas implanted in humans has been conducted so far. In 2010, the team led by Professor May Griffith of Linkoping University (Sweden) used a model composed of a collagen gel in a group of 10 patients with pathologies in the most anterior region of the cornea. According to González-Andrades, "at first, it was going well, but then they saw that they weren't achieving all the visual acuity they had hoped for, and the model was halted to work on improving its strength and manageability."

Unlike this system, the cornea proposed by the González-Andrades team is composed of an artificial matrix on which a layer of epithelial corneal cells is placed (the epithelium is the most superficial part of the cornea). This matrix is ​​formed by agarose (a biomolecule that comes from an alga), and by fibrin, a protein obtained from blood plasma essential for the formation of clots. Within this fibrin-agarose scaffold, the researchers introduce cells from the stroma, the second layer of the cornea, which accounts for more than 90% of its total thickness. The two populations of corneal cells that they use, epithelial and stromal, come from cultivating small pieces left over from donor corneas after a conventional transplant in the laboratory. 

Seeking complete corneal replacement

Although in clinical practice it is possible to replace the corneal epithelium with cells generated in the laboratory to treat patients who have lost the ability to regenerate this layer, this procedure only solves part of the cases. In addition, it is an expensive treatment and it is not performed worldwide. González-Andrades, on the contrary, seeks a complete regeneration of the cornea: to be able to remove it entirely when it is damaged and to place a new one. 

At the moment, the fibrin-agarose cornea created by this young man replaces both the epithelium and the stroma, and his team continues to search for a way to recreate the third layer, the endothelium, a very thin sheet of a single cell thick located in the innermost part and especially difficult to imitate. 

Unlike patients with more superficial damage, the ones González-Andrades is recruiting for his trial have ulcers that have affected both the epithelium and the stroma, and for which there is currently no standardized or optimal treatment. According to the researcher, "these are extreme patients, where all is lost, and not even a corneal transplant can be performed because it will almost certainly be rejected."

González-Andrades states that, so far, in vitro tests with his fibrin-agarose prototype have resulted in very good levels of transparency and total absorption of ultraviolet radiation (similar to the natural cornea). Experiments in rabbits have also yielded good results in transparency and integration. He adds: "Now, depending on the results with patients of this type, its application could be extended to other corneal pathologies."

In addition to this model, this innovator is also working on two other possible corneal configurations: one based on decellularizing animal corneas and then introducing human cells; and a multilayer model of collagen sheets that "overlap with a certain orientation and improve transparency." One of the possible lines González-Andrades is considering pursuing in the future would involve combining several of these approaches and manufacturing multilayered fibrin-agarose corneas.

For this young man, who currently divides his time between university and the Ophthalmology Department at San Cecilio Hospital in Granada, research has always been "a hobby and a source of fun," and he acknowledges that he's unable to understand clinical practice without research, nor research without clinical practice. "When a patient asks you, 'Isn't there something else?' and you're unable to provide a solution to their problem, it's time to move to the laboratory and start researching," explains González-Andrades.

According to Carmen Eibe, director of project coordination for the Zeltia Group and member of the jury for the MIT Technology Review Innovators Under 35 Spain awards, this young innovator presents a "concrete and promising project." She emphasizes that the development of artificial corneas is "a field of great industrial and therapeutic application" that, once it reaches the market, "will provide significant benefits."