Meet our researchers: Dr Karl Brown
Research Fellow, Corneal Research
Dr Karl Brown is a research scientist working to develop engineered tissues and cell therapies to treat corneal disease.
What inspired you to pursue tissue engineering – specifically in corneas?
When I came to CERA, I was asked: “Why are you interested in studying the eye?” Truthfully, I wasn’t really interested in the eye itself but rather in tissue engineering – and the cornea is a great model for that.
One of the biggest hurdles faced in tissue engineering is connecting blood vessels, but the cornea doesn’t have any blood vessels. It’s a simple structure with three types of cells. You could say I was attracted to studying the eye – and the cornea in particular – because it seemed like it was really ‘do-able’ for tissue engineering.
Tissue engineering in many ways is a creative pursuit – every day you see problems and must think about the materials, processes and capabilities you need to solve those problems.
I left school set to be an artist. That didn’t work out, but the skills I learned in combinatorial thinking and forced creativity I use every day in science. I get to test solutions and see how cells behave, and then see my creative solution succeed or fail.
What is the most innovative or exciting aspect of your research?
We’re working on a tissue-engineered corneal endothelium, using a synthetic hydrogel produced by our University of Melbourne collaborators.
We grow the cells in a flat sheet on the hydrogel, which is half the thickness of a human hair but really strong and transparent. We then place the sheet onto the back of a diseased cornea, and then the hydrogel dissolves and you’re left with the cells.
In Australia, we’re lucky because organisations like the Lions Eye Donation Service (LEDS) can obtain many corneas, but other developed nations suffer from shortages and run out. This has the potential to replace around sixty per cent of corneal transplants in developed nations, and treat many patients waiting for tissue in developing nations, which is important because there is a massive shortage of donor corneas.
Another exciting thing is we’re part of the MRFF-funded BIENCO consortium to produce a full-thickness cornea, which, in its final form, would completely replace corneal transplants. I sometimes joke with LEDS that they’re helping me to put them out of business. The reality, of course, is we’ll need donor tissue for transplant for many years yet.
What are the potential real-world outcomes you could imagine arising from your research?
A tissue-engineered corneal endothelium will restore vision to a lot of people who otherwise would not be able to get donor tissue. You only have so many corneal endothelial cells and gradually lose them over time. If humans live long enough, eventually you just won’t have enough. Currently, most people have enough to last a lifetime, but if the corneal endothelium is damaged, it does not repair itself and many eventually need a transplant.
Why is it important to come up with therapies to replace transplantation?
In developed nations, there are shortages of corneas for transplantation. The issue is worse in developing countries, so I’d like to see tissue-engineered corneas there first.
I also hope the treatment we create will be cheaper than transplanted tissue. If you think about every corneal transplant from a donor, it is bespoke tissue. A team of people have to find a donor, retrieve the tissue, store it and then prepare it.
There is a misconception that emerging treatments will all be high tech and expensive, and only rich people will be able to afford them. If we can mass produce tissue-engineered corneas, it will hopefully be cheaper.
Why are collaborations important for tissue research?
No single laboratory has the capacity to produce a tissue-engineered treatment – particularly in Australia where the labs are quite small. If you want to kick goals, you must work together.
If you want high-impact papers, you either need to be lucky and find something no one else has noticed, or collaborate and bring together cutting-edge techniques to uncover information that couldn’t be found without using those new techniques.
We collaborate with chemical engineers, immunologists, clinicians, cell biologists and people who do single-cell genomic sequencing. Other important collaborators are people who work in eye donor organisations and commercial people to understand if this makes economic and logistic sense.
As part of the BIENCO consortium, we’re involved in an interesting collaboration with a group in Wollongong. They have a process called electro-compaction that uses magnetic fields to align collagen fibres at a microscopic level.
They make a mat out of that and then rotate the magnetic field and put another layer down. This mimics the fibres the cells make inside the cornea. I can’t do that!
Tissue engineering is really at the pointy end of the need for collaboration, because of the nature of what we are trying to do. We need all this expertise that in previous generations were placed in separate silos.