Making heart valves from collagen

Researchers from Carnegie Mellon University have developed a way of 3D printing components of the human heart, which could be beneficial considering there are around 7.4 million people in the UK living with heart and circulatory disease. The parts are made of collagen, the main structural protein in our bodies, and they work just like real heart tissue.: Printing collagen has been a major hurdle in biomedical engineering, but now the team has made a big leap forward. Andrew Hudson, one of the lead authors on this paper, spoke to Phil Sansom...

Phil - A group of biomedical engineers at Carnegie Mellon University have been working on something amazing: 3D printed bits of human heart. It's all thanks to their special 3D printing technique called FRESH.

Andrew - Fresh stands for Free-form Reversible Embedding of Suspended Hydrogels, and this is a technique that's pretty powerful in that it kind of allows us to 3D print fluids.

Phil - That's researcher Andrew Hudson. He says the reason it's helpful to print a fluid, is that you can print collagen. Collagen is a protein, the most abundant protein in our bodies. Some have called it the holy grail of bio-prints, and it's very difficult to 3D print.

Andrew - Even just printing, really, any length scale of any material or any geometry from collagen has been very, very difficult for the field.
 
Phil - That's because to get collagen into a useful gel form, you have to print it when it's still a liquid.

Andrew - And if you were to just try and 3D print that in air it would collapse on your build plate, you'd end up with a puddle.

Phil - People have tried to solve this by solidifying it with gelatin, but the end result isn't very natural. The FRESH technique takes a different approach.

Andrew - We 3D print inside a tub of support material, and that support material has a really important physical property in that it has what's called a yield stress, and what that means is; there is a minimum amount of force that you have to exert on this material and then it starts flowing like a fluid. It's very similar to mayonnaise, where if you turn a jar of mayonnaise upside down it doesn't slosh to the bottom because it has a yield stress. But whenever you can scoop it out with your knife you can spread it on bread because at that point you're shearing it enough so that it can start flowing like a fluid. So what we're printing into, has that physical property and that's what allows us to inject material into it, and then have it be cushioned and prevent it from collapsing during the printing process.

Phil - This support material, the lab’s own secret sauce, is what they've really improved in their recent paper. They've been able to 3D print at much higher resolution by making the particles of the support material smaller.

Andrew - And you can think of it, really, much like drawing a picture in the sand at the beach. So if you try and draw say, the Mona Lisa in gravel, you can't get as much of a high resolution picture as if you were to try and print in fine sand. Now in that analogy the precision with which I can move my hand is just dictated by how expensive is your printer and what hardware do you have, the thickness of my finger is just analogous to the width of my needle, and then, the most important part which is what we've improved upon in this paper is reducing the size of those particles to try and therefore get a higher resolution picture that we're trying to print layer by layer.

Phil - With this fine control they can print all sorts of structures from cylinders, to networks of tubes that are like arteries and veins.

Andrew - So in the paper what we had done, we had taken patient specific data from someone's heart arteries, and then we merged that and we kind of, computationally filled in some gaps and so we have this really interesting structure that's combined of patient based data, along with computationally generated tubes.

Phil - They can even 3D print a custom heart valve.

Andrew - Notably we made the first proof of concept, functioning heart valve. And there's a huge market in terms of heart valve replacement, heart valve repair.

Phil - At the moment, there are two treatments to replace heart valves. You can either get mechanical ones or bio-prosthetics. The mechanical ones are often metal and can be really well engineered but there's a high risk of blood clotting, so you need to be on blood thinners for the rest of your life. Bio-prosthetics might be from a pig or a cow, and you won't need blood thinners but these don't last nearly as long.

Andrew - We can kind of combine the best of both worlds with bioprinting, where we can in theory, have engineering design and all the criteria that we can simulate before we build anything first, but we can print it from the materials that we know, that we like from bio prosthetic valves that are very blood compatible. It's obviously a very long 10 plus year regulatory pathway but we're really excited to try and actually do patient specific bioprinted medical devices.

Phil - Andrew Hudson and his colleagues see a massive scope for this FRESH 3D printing technique.

Andrew - What's really powerful about our technique is that we can use it on printers that cost around 1,000 dollars. The current bioprinters go from a bare minimum of 10,000 up easily to a million. And what we think we show very convincingly in our paper, is that the hardware that you have does not matter as much as how you print these things. And we're really showing that with just a 1000 dollar 3D printer, using the FRESH technique you can outperform a one million dollar printer. So it's very realistic to have any university, even high school start to have bioprinters. So we're really driving down the cost of bioprinting and really trying to get more people into the space so that they can innovate.