With a growing need for donor corneas, researchers are looking for new ways to meet tissue demand. Enter the self-curving cornea. Created by a team at Newcastle University’s Institute of Genetic Medicine – responsible for the first 3D printed cornea – these ‘self-curving’ biological tissues take just five days to develop. In the study, a flat circle of stromal cells – derived from limbal rings left over from corneal transplantation – were activated by a serum that caused the edges of the circle to contract at a different rate to the cells at the center. The result is a bowl-shaped structure similar to that of a human cornea.
So how did the idea come about? “A few years ago, we discovered that a particular peptide amphiphile had an RGD sequence similar to that of collagen, and that cells recognize peptides in that sequence and, as a result, bind readily to them.” explains Che Connon, Professor of Tissue Engineering at the University. “We were making a gel of the RGD peptide amplifier and found that cells didn’t contract very much – even in the presence of serum, whereas cells in a collagen gel without peptides will readily contract in a serum medium,” says Connon. “We then thought if you can spatially localize the peptides within a 3D gel, then you can infer shape into the contraction.” And that’s what they did. Indeed, the team spent a lot of time investigating the effect that shape has on corneal cell function.
“The curvature isn’t just important for refractive purposes. Recent papers have shown that corneal stromal cells actually change their type if they are grown in a curved environment. The cells have developed and evolved within a curved material and only behave appropriately (by which I mean, form aligned collagen, which is the structural part of the cornea) in a curved environment,” explains Connon. “And that’s why we created two forms of hydrogel – one that the cells can bind to and pull against, and another where the cells can’t. If you position those hydrogels next to each other within a contiguous system, you will find that one half of the overall hydrogel will contract and the other half will not – it is this combination that infers a shape overall.”
Though there are other ways of manufacturing corneas, such as 3D printing, a relatively simple approach to generating transplantable corneas is advantageous, says Connon. Though the concept is still in its infancy, the team hopes that the principle can be applied elsewhere in the body. “Imagine a tubular vessel, which could contract in response to certain factors flowing through that tube – like a stent placed into the heart,” says Connon.
“Just the idea of being able to create complex shaped tissues in response to external environment is a game changer.”
