Bioprinting isn’t a new phenomenon. In fact, research into the printing of various body parts has been going on since the late 1990s. It’s potentially offering medical professionals alternative ways of conducting medical transplants. For 20 years, Che Connor, Professor of Tissue Engineering, Newcastle University has had his focus on the component of the eye that gives us the ability to focus in the first instance. After successfully printing a customised human cornea, TCT Magazine asked how and why.
Can you explain why there is a need for this kind of research to be undertaken?
Che Connon (CC): Globally, there are almost 5 million people who are corneal blind in both eyes, and the people that are corneal blind in one eye raises that number to 23 million. Currently, corneal donor tissue transplantation is the only widely accepted treatment to restore sight. It’s estimated over 12 million people are on a waiting list for transplantation. There’s a severe shortage of donor corneas worldwide, and that means only 1 in 70 individuals in need receive transplants. Another point is that over 50% of the world’s inhabitants don’t have access to corneal transplantation. That’s why this work needs to be done.
Can you explain how the process of bio-printing a human cornea works?
CC: We take a population of corneal stromal stem cells that sit inside the corneal matrix, extract those cells, grow them up and then combine them with a bio ink. The bio ink is extruded through the printer to make a printed tissue. It needs to have several attributes. It needs to flow. It needs to maintain viable cells. And it needs to have enough mechanical properties to hold its shape following the extrusion. We developed a novel bio ink that contains collagen, one of the main structural components of the cornea. We combine that with alginate, a polysaccharide derived from seaweed, which has some good characteristics: it’s very self-friendly, it also cross links and forms a very stable matrix without harming the cells. Once we have that bio ink, we extrude it into a mould which has been taken from an actual patient’s corneal shape. That data is collected using normal ophthalmic cameras that they use for fitting contact lenses. That gives you the shape of the cornea. We recreate the negative images of that cornea in a mould, and then we extrude the positive image through the bio ink into that mould, holding its shape, forming a corneal shaped tissue that has the appropriate stromal cells within it.
How important is customisation for 3D printed corneas to work in the human body?
CC: The shape of the cornea is important in terms of transplantation and that isn’t easily addressed with the current systems for donors. The shape of your donor cornea is not bespoke and that can cause problems with the patient’s vision, stigmatism, for example, is often caused by a poor match of the shapes of the donor tissue with the patient’s own eye. With 3D printing, you should have complete control over the final shape of the tissue. That means the patient’s vision should be predictable following that transplant.
What were the biggest challenges you faced during this research?
CC: These challenges have been addressed over 20 years of my research. They include how you extract and grow the cells appropriately so they maintain the right phenotype, the right function; what materials can you use to mix them with; and also when we print the cornea, we are giving the cells within that printed cornea very specific cues, which then direct those cells to become organised in a way that they would do in the normal cornea. Some of those challenges were ‘what are those cues? What is it inside a normal cornea that directs those cells to be corneal-like?’ And it’s our understanding of those cues which form a fundamental part of our breakthrough technology.
And what challenges lie ahead?
CC: One challenge is how do we keep the printed cornea in place once it is transplanted. We need to think about how exactly they are going to surgically implant this cornea. Is it going to be sutured? Is it going to be glued? This is a challenge we face.
How much of an impact do you think this research can have?
CC: The need for corneal transplants is growing. Our idea with a 3D printing approach is that it facilitates the manufacture at the site of need. The printing process should be low cost so the impact will come from having accessibility to corneas at an affordable price. A combination of those two will lead us to have a real impact across the world.”