November 2018

NEWS & OPINION
Meet the first 3D-printed “human” cornea

by Liz Hillman EyeWorld Senior Staff Writer


Dr. Connon (left) and Dr. Swioklo (right) watch a 3D cornea made of human corneal stromal cells being printed.

Dr. Swioklo and Dr. Connon show a dyed, 3D-printed cornea.
Source (all): Newcastle University

Watch a video of this
process on EWAR

Human corneal stromal cells printed with a bio-ink that is shelf stable for more than 1 week

For more than 2 decades Che Connon, PhD, professor of tissue engineering, Newcastle University, Tyne, U.K., has been working with corneal cells. Most recently, his work led to the development of the first 3D-printed cornea made with human cells.
There are several conditions that might require corneal transplants. And while several procedures are available to address this need, for those that require a graft, there is a “world shortage” of donor tissue, Dr. Connon said, prompting the desire for an on-demand tissue source that’s not reliant upon human donors but meets similar biocompatibility, safety, and efficacy standards.
“Working toward the 3D-printed cornea is a good way of addressing this need,” Dr. Connon said.
In the journal Experimental Eye Research,1 Dr. Connon and coresearchers Steve Swioklo, PhD, and Abigail Isaacson, guest researcher, Institute of Genetic Medicine, Newcastle University, describe how they used 3D “bio-printing” to create corneal structures that were similar to that of the human cornea with a “collagen-based bio-ink containing encapsulated corneal keratocytes.” The keratocytes in this 3D-printed cornea showed high viability at day 1 and 1 week post-printing.
The cornea printed by the team was a curved tissue. In separate research, Dr. Connon and his team discovered that the curvature of the cornea, in addition to being responsible for some refractive properties, actually affected the corneal cells (keratocytes).
“The keratocytes respond to a curved surface and align in response to that curved surface. What we’ve taken from that is that the curvature of the eye is also important for the maintenance of keratocytes within it,” Dr. Connon explained. “When we’re looking at making an engineered cornea, we knew we wanted to create a curved tissue because this would be a cue for the cells within it to behave appropriately, given enough time.”
Dr. Connon said the printer they used was relatively cheap (about $8,000), and that decision was made on purpose with the idea being that the technology could someday be accessible to doctors around the world.
“We’re thinking ahead, and also because we think that it’s not necessary to create every single facet of the cornea. We don’t need to print in the finest possible detail. We’ve previously shown cells can do that fine tuning, under the right conditions,” Dr. Connon explained.
The ink itself is composed of collagen and a polysaccharide extracted from seaweed that, as Dr. Connon put it, “gives it the right characteristics to keep cells alive.” What’s more, it’s extrudable but also stable enough to hold its shape once printed. The keratocytes with the hydrogel encapsulation technology are shelf stable for several weeks in a sealed tube.
“For printing, we’re thinking ahead and imagining a situation in a doctor’s surgery [where] they have a 3D printer in the corner of the room and there they have a range of inks containing cells that are sealed and can be stored for days or weeks, and the doctor takes the bio-ink off the shelf, plugs it in the printer, and immediately prints an eye, cornea, skin, or some other tissue,” Dr. Connon said.
The hope in the future is that this technology could be used to print on-demand, customized corneas of the correct size and matching patient’s refractive needs, but there are a number of challenges that remain.
Dr. Connon said this paper provides a proof-of-principle that you can take a topographical image of a patient’s cornea, render it in 3D on a computer, and recreate the corneal shape on a 3D printer using corneal stromal stem cells in a bio-ink.
“The challenges will be numerous but the first one would be, what needs to be done to that printed cornea to make it perhaps suturable, for example. How is it going to be transplanted directly into the eye, how will it stick in there? … Then there are safety and efficacy studies in animal, into human, etc., that would need to be done,” Dr. Connon said.
Dr. Connon and coinvestigators are not alone in their work using 3D printing to solve ophthalmic problems. Kyle Packer, MD, a captain in the U.S. Army, and chief of refractive surgery, Womack Army Medical Center, Fort Bragg, North Carolina, is working on developing a 3D-printed biomaterial for simulation training purposes. Dehghani et al. designed a 3D-printed membrane for conjunctival reconstruction and found it could offer a “promising” alternative to amniotic membrane use.2 3D printing has been used to customize orbital implants for facial reconstruction and as a planning tool for stereotactic radiosurgery in eyes with uveal melanomas.3,4 3D printing has also been used to create a “smart storage glide” for the preservation and delivery of posterior lenticules for Descemet’s stripping automated endothelial keratoplasty, used to model fundus range viewing research, and more.5,6

References

1. Isaacson A, et al. 3D bioprinting of a corneal stroma equivalent. Exp Eye Res. 2018;173:188–193.
2. Dehghani S, et al. 3D-printed membrane as an alternative to amniotic membrane for ocular surface/conjunctival defect reconstruction: an in vitro & in vivo study. Biomaterials. 2018;174:95–112.
3. Callahan AB, et al. Low-cost 3D printing orbital implant templates in secondary orbital reconstructions. Ophthalmic Plast Reconstr Surg. 2017;33:376–380.
4. Furdova A, et al. Early experiences of planning stereotactic radiosurgery using 3D printed models of eyes with uveal melanomas. Clin Ophthalmol. 2017;11:267–271.
5. Ruzza A, et al. Preloaded donor corneal lenticules in a new validated 3D printed smart storage glide for Descemet stripping automated endothelial keratoplasty. Br J Ophthalmol. 2015;99:1388–95.
6. Xie P, et al. Application of 3-dimensional printing technology to construct an eye model for fundus viewing study. PLoS One. 2014;9:e109373.

Editors’ note: Dr. Connon has no financial interests related to his comments.

Correction: This article was updated in March 2019 to correct Abigail Isaacson’s affiliation with the university as a guest researcher. EyeWorld had erroneously misidentified her as a doctoral student and apologizes for the error.

Contact information

Connon: Che.Connon@newcastle.ac.uk

Meet the first 3D-printed “human” cornea Meet the first 3D-printed “human” cornea
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