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 (carried out with a cornea from a donor) and through the implantation of so-called keratoprostheses (non-biological artificial corneas). As far as the first option is concerned, donors are scarce, and they will be more and more so given the growing popularity of operations to correct defects such as myopia, in which the corneas of those who undergo them are rendered useless to be transplanted. For their part, keratoprostheses have several disadvantages: they are expensive and have a high risk of complications, which requires 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, highlights the “undeniable need to develop optimal human artificial corneas”.
Despite this urgency, so far only one complete biosynthetic artificial corneas implantation trial has been carried out in humans. In 2010, the team led by professor at Linkoping University (Sweden) May Griffith used a model made up of a collagen gel in a group of 10 patients who presented pathologies in the most anterior area of the cornea. According to González-Andrades, "a priori it went well, but then they saw that they did not gain all the visual acuity they wanted and the model stopped to work on improving its resistance and handling."
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, those that González-Andrades is recruiting for his trial have an ulcer that has affected both the epithelium and the stroma and currently does not have a standardized or optimal treatment. According to the researcher, "these are extreme patients, where everything is lost and not even a cornea transplant can be done because it will almost certainly be rejected."
González-Andrades assures that, for the time being, in vitro tests with his fibrin-agarose prototype have resulted in very good levels of transparency and total absorption of ultraviolet radiation (the same as the natural cornea). Experimentation in rabbits has also yielded good transparency and integration results and 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 to then introduce human cells; and a multilayer model of collagen sheets that "overlap with a certain orientation and improve transparency." One of the possible lines that González-Andrades is considering undertaking in the future would consist, precisely, in combining several of these approaches and fabricating multilayer fibrin-agarose corneas.
For this young man, who currently divides his time between the university and the Ophthalmology Department of the San Cecilio Hospital in Granada, research has always been "a hobby and fun", and he admits that he is not capable of understanding clinical practice without research or non-clinical research. “When a patient asks you “and isn't there something else?” and you are unable to solve their problem, it is time to go to the laboratory and start investigating”, explains González-Andrades.
In the opinion of the project coordination director of the Zeltia Group and member of the jury of the MIT Technology Review Innovators under 35 Spain awards, Carmen Eibe, this young innovator presents a project "concrete and with a great future", and highlights that the development of artificial corneas is "a field of great industrial and therapeutic application" that when it reaches the market "will provide great benefits".