In most cases, a patient with a blocked or damaged blood vessel in their heart will rely on a procedure to treat their condition called an autograft. During the surgery, a large vein is harvested from elsewhere in the body, such as from the leg, and used to repair or bypass the faulty vessel in the chest. It’s a highly invasive procedure, which many older patients can be too frail to undergo. While synthetic vascular grafts are also available, they are prone to infection and blood clotting in smaller diameter vessels – but this is where tissue engineering can start to come in handy.
University of Sheffield research fellow Dr Sam Pashneh-Tala is pioneering the study of cardiovascular disease through scaffold based stereolithography (SLA) tissue engineering techniques powered by the Formlabs Form 2 3D printer. The scaffolds enable him to construct blood vessels with complex geometries, which can be customised to the vascular contours of individual patients.
The mould is designed with Solidworks CAD software, and the desired shape is printed with the Formlabs 3D printer. The moulds are then assembled and secured on top of each other with a cavity in the centre, which is filled with a custom biodegradable polymer emulsion developed by Pashneh-Tala and his colleagues. When the polymer sets, a porous scaffold with microscopic holes that the cells can grow into is left behind. Over time the structure will dissolve, leaving just the cells in the desired shape.
Once the scaffold has been seeded the with patient’s cells, it needs to be cultured inside a bioreactor. The Sheffield researchers use the Form 2 SLA printer to do so, meaning they can design and print a new piece of tissue within a matter of hours.
Straight vessels are more complex for surgeons and less primed for the natural shape of the body, but growing tissue around 3D printed scaffolds has proven itself an ideal solution to the problem. Pashneh-Tala is able to create organic, custom moulds freely with same-day iterations, and has brought rapid prototyping to his laboratory. In an interview at the recent Formlabs User Summit 2019 in Berlin, he discusses the potent combination of 3D printing and tissue engineering.
Chloe Kent: What are you currently working on?
Sam Pashneh-Tala: I’m a tissue engineer at the University of Sheffield. I focus on tissue-engineered blood vessels and associated things, such as vein valves. I have two separate undergrad degrees in biology and mechanical engineering, two very different disciplines which are really combined now in what I do.
I wanted to produce blood vessels in different shapes. There were people doing blood vessels, they were doing quite well there in clinical trials. But everything was just a straight tube; I couldn’t really see how they were going to be able to do different shapes, and there are lots of different shapes of blood vessel. So we really built this method from the ground up, in terms of making these scaffolds that we grow cells on, and then producing bioreactors where we culture these vessels in the lab.
I have projects on vascular graft, developing blood vessels for use in clinics, and vein valves are a new project. I also now work on growing blood vessels for use in research, so if you’re a company that’s making stents or synthetic vascular processes, rather than testing on an animal vessel or some sort of synthetic silicon, I’m trying to grow a better test platform.
CK: How is testing on a lab-grown human vessel superior to animal or silicone?
SPT: We don’t know yet, that research has only just begun. The company I’m working with, Terumo Aortic, is a leading vascular device manufacturer and they use silicon tubes to test their devices on, or they get bovine aortas from the abattoir. Animal tissues can be of variable quality and they degrade quite quickly.
The hope is that we can produce a lab-grown vessel that is better than those two platforms in terms of its mechanical properties. Something we can definitely do that those platforms don’t do is try to measure some sort of biological response as well, seeing how endothelial cells inside a blood vessel respond to a certain stent.
CK: What are the advantages of implanting this kind of tissue over donor tissue?
SPT: With transplants of organs nowadays, rejection is a major problem. You can do tissue matching between individuals, but transplant recipients generally have to be on rejection drugs for their whole life. The advantage of tissue engineering is that if we do a patient map solution, take your cells, make tissue for you and implant it back into you, there are no logical rejection issues. Your body doesn’t notice the difference.
CK: Which 3D printers have you used in your work?
SPT: I use the Formlabs Form 2 printer most extensively in my work. Before this, is used the Form 1 and the Form 1+ – I’ve had all the Formlabs products. I have also used an Ultimaker 2+ printer for some parts of my research work and a Kudo3D Titan 2 for experimenting with new print materials.
CK: Where do you see the medical applications of 3D printing going in the future?
SPT: Medicine really is one of the places where 3D printing is going to have a huge impact because of the power you get in terms of having a customised and personalised solution. All of us are unique and even stratified solutions don’t work for everybody, but 3D printing can make it economically viable to give patients personalised prosthetics or tissues.
In terms of what I do, I think it’s going to enable me to produce patient-matched tissues. My vision is to produce and engineer vascular grafts which are designed specifically for individual patients’ clinical needs and anatomy. Going beyond that, bioprinting has a long way to go but it’s powerful as well in terms of being able to reproduce the complexity of our bodies.
We’re talking about establishment over decades, but I think in 50 to 100 years’ time we might look back and think how it was incredibly archaic to have this system where we tried to treat everybody with the same device or drug.