Perspective

Biomimetic 3-D printed corneas may revolutionize corneal transplantation

This new technology has potential to create highly biocompatible customized grafts tailored to individual patients.

A biomimetic cornea that combines stem cell technology and 3-D printing may be the future of corneal transplantation.

“Research is still at the early stages, but what the future may bring is a customized graft, perfectly tailored for the patient, derived from the patient’s own cells, with no risk of rejection. A concept that is entirely different from the types of artificial corneas we have now, and also a potential solution to the cornea transplant tissue shortage that is currently a global concern,” Nadia Zakaria, MD, PhD, said.

The project of 3-D printed biomimetic corneas, co-funded by the Belgian government, involves the University of Antwerp and the Catholic University of Leuven, Belgium.

Nadia Zakaria

“It is a very interdisciplinary project because my background is ophthalmology, stem cells and regenerative medicine, but we needed engineers on board and biomaterial manufacturing experts,” Zakaria said.

The technology of computer-aided design and 3-D printing has raised increasing interest as a potential resource for tissue engineering. What it entails is a layer-by-layer deposition of tissue to create biomimetic 3-D models of any shape and architecture. One of the groups researching in this area is the Wake Forest Institute for Regenerative Medicine, currently working to print kidney tissue.

“An enormous challenge, mainly because you have an enormous amount of blood vessels, so it’s a very complex organ that needs to be designed,” Zakaria said.

The human cornea, she said, is more easily reproducible because it is small, has a defined shape and curvature, and is completely devoid of blood vessels. In addition, the stroma is essentially made of one cell type, the keratocyte.

Winning combination with femtosecond laser

With the advent of the femtosecond laser, corneal transplantation has overcome suture-related issues and has achieved a high degree of customization. Combination with 3-D printing could become another step toward tailoring the corneal graft to each patient.

“With the Pentacam measurement, Scheimpflug imaging and 3-D rendering, you can determine what the ideal curvature would be to have the best possible correction post-PK. I am talking about the future here, but the idea, the vision, is someone comes in, has his or her scan done, and we determine what the optimal geometry is. This would be a huge step forward because now patients on a waiting list can only accept whatever corneas become available. There is no matching for geometry done whatsoever right now,” Zakaria said.

The combination of these new technologies “allows us to start thinking along these lines,” she said. Corneas of micron-perfect thickness and curvature could be 3-D printed for individual patients, and the femtosecond laser could create a matching bed where they fit with no sutures, leading to precise vision.

Work in progress

“This is what we aspire to. Of course, we have a long way to go. We are now able to print with a resolution of 1 µm to 4 µm, and we are still working on developing samples between 20 µm and 60 µm thick. We need to go much further to full-thickness grafts of 400 µm to 500 µm with a much higher resolution,” Zakaria said.

The group has been working with recombinant human collagen type 3 as a bio-ink for printing. Samples have been tested for biocompatibility and have been used as a scaffold for primary human corneal stroma-derived mesenchymal stem cells cultured in vitro. In vivo data may be available as soon as this year.

“That’s where we are. First of all, we have to make sure that the printing process doesn’t alter the collagen in any way. Then, we must test biocompatibility in animals. Human clinical trials will follow, but we are not there yet. Meanwhile, 3-D printing technology is moving fast,” Zakaria said.

“It all looks very promising. Besides the advantages of customization, there is biocompatibility because each graft could be made from the patient’s own mesenchymal or corneal stem cells, with no risk of rejection or disease contamination. In addition, although producing tissue is not going to be cheap, additive manufacturing reduces the costs and produces very little wastage,” she said. – by Michela Cimberle

Disclosure: Zakaria reports no relevant financial disclosures.

A biomimetic cornea that combines stem cell technology and 3-D printing may be the future of corneal transplantation.

“Research is still at the early stages, but what the future may bring is a customized graft, perfectly tailored for the patient, derived from the patient’s own cells, with no risk of rejection. A concept that is entirely different from the types of artificial corneas we have now, and also a potential solution to the cornea transplant tissue shortage that is currently a global concern,” Nadia Zakaria, MD, PhD, said.

The project of 3-D printed biomimetic corneas, co-funded by the Belgian government, involves the University of Antwerp and the Catholic University of Leuven, Belgium.

Nadia Zakaria

“It is a very interdisciplinary project because my background is ophthalmology, stem cells and regenerative medicine, but we needed engineers on board and biomaterial manufacturing experts,” Zakaria said.

The technology of computer-aided design and 3-D printing has raised increasing interest as a potential resource for tissue engineering. What it entails is a layer-by-layer deposition of tissue to create biomimetic 3-D models of any shape and architecture. One of the groups researching in this area is the Wake Forest Institute for Regenerative Medicine, currently working to print kidney tissue.

“An enormous challenge, mainly because you have an enormous amount of blood vessels, so it’s a very complex organ that needs to be designed,” Zakaria said.

The human cornea, she said, is more easily reproducible because it is small, has a defined shape and curvature, and is completely devoid of blood vessels. In addition, the stroma is essentially made of one cell type, the keratocyte.

Winning combination with femtosecond laser

With the advent of the femtosecond laser, corneal transplantation has overcome suture-related issues and has achieved a high degree of customization. Combination with 3-D printing could become another step toward tailoring the corneal graft to each patient.

“With the Pentacam measurement, Scheimpflug imaging and 3-D rendering, you can determine what the ideal curvature would be to have the best possible correction post-PK. I am talking about the future here, but the idea, the vision, is someone comes in, has his or her scan done, and we determine what the optimal geometry is. This would be a huge step forward because now patients on a waiting list can only accept whatever corneas become available. There is no matching for geometry done whatsoever right now,” Zakaria said.

The combination of these new technologies “allows us to start thinking along these lines,” she said. Corneas of micron-perfect thickness and curvature could be 3-D printed for individual patients, and the femtosecond laser could create a matching bed where they fit with no sutures, leading to precise vision.

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Work in progress

“This is what we aspire to. Of course, we have a long way to go. We are now able to print with a resolution of 1 µm to 4 µm, and we are still working on developing samples between 20 µm and 60 µm thick. We need to go much further to full-thickness grafts of 400 µm to 500 µm with a much higher resolution,” Zakaria said.

The group has been working with recombinant human collagen type 3 as a bio-ink for printing. Samples have been tested for biocompatibility and have been used as a scaffold for primary human corneal stroma-derived mesenchymal stem cells cultured in vitro. In vivo data may be available as soon as this year.

“That’s where we are. First of all, we have to make sure that the printing process doesn’t alter the collagen in any way. Then, we must test biocompatibility in animals. Human clinical trials will follow, but we are not there yet. Meanwhile, 3-D printing technology is moving fast,” Zakaria said.

“It all looks very promising. Besides the advantages of customization, there is biocompatibility because each graft could be made from the patient’s own mesenchymal or corneal stem cells, with no risk of rejection or disease contamination. In addition, although producing tissue is not going to be cheap, additive manufacturing reduces the costs and produces very little wastage,” she said. – by Michela Cimberle

Disclosure: Zakaria reports no relevant financial disclosures.

    Perspective

    Gary N. Wörtz

    Technology is advancing that allows ophthalmologists and patients to consider new options for corneal refractive, therapeutic and regenerative treatments. Three-dimensional printing has many nonbiological applications, and it may have crossover applications in designing and creating human tissue from host cultured components. And, if tissue printing becomes a reality, the cornea will likely be the first viable product.

    This technology, while vastly interesting and exciting, will clearly need to be developed and tested to prove safety and benefit above our current options. We are not there yet, but we can perhaps give our patients with corneal pathology more hope for the future.

    • Gary N. Wörtz, MD
    • OSN Technology Board Member

    Disclosures: Wörtz reports no relevant financial disclosures.