Printing Living Tissue Within Seconds
A technology with science fiction qualities: one second, you are staring at a solution in a barrel and just a few seconds later, you are looking at an object that literally appeared out of nowhere. The nerds among us will quickly recognise the resemblance of 3D volumetric printing to Star Trek-style teleportation; the only difference is that the materialising object has never existed before – only as code. Objects materialise by projecting a laser hologram through a rotating barrel that contains a light-responsive solution. The object is created by solidification of the solution at the locations where the light is directed.
RMU researcher Paulina Nuñez Bernal visited the École Polytechnique Fédérale de Lausanne (EPFL), Switzerland, to learn this fascinating technique and to be the first to merge it with biological components. Her goal was to apply 3D volumetric printing to create complex living structures. A few months later, Paulina and her colleagues published a paper, in which they describe the printing of ears, menisci and bones.
I met Paulina to get a glimpse behind the scenes.
Hello Paulina! Please, tell us who you are.
Sure! My name is Paulina, I am originally from Mexico and have lived in Europe for 10 years. I went to high school in Germany and moved to Utrecht for my Bachelor’s and Master’s. My academic background is pretty broad; mostly biology focused, but I also did my bachelor’s in liberal arts, so I was able to do a minor in psychology as well. I have a master’s degree in Regenerative Medicine and Technology, and now I am doing my PhD at the department of Orthopedics at the Regenerative Medicine Center Utrecht (RMCU, UMC Utrecht).
Only a few months have passed since you started your PhD, and you already published a paper that attracted quite some media attention!
Yes, it was really cool to get this much attention from the media! I was in Switzerland for a month, and I am still amazed about how fast the whole process went, from initial pilots to the actual publication. My supervisor, Dr. Riccardo Levato, became aware of this technique, and swiftly contacted the inventors of the printer in Switzerland. They were eager to collaborate and invited us to visit for a few days. We brought some material with us for feasibility studies, and it went surprisingly well.
So, I went back, this time with cells and a lot of materials. The research group I worked with has no biology facilities, so we had to work with another group in the building and set up our own cell-culture on the other end of the facility. After this, it was all about culturing the cells and keep printing, printing, printing. Any set-back in the beginning like infections or failed prints would have delayed things for weeks and thwarted the whole mission. But the odds were in our favor and we managed to complete the main experimental work during the month I was there!
In your view, what is so special about your publication?
I would say it is science fiction feel of the technology. I think and hope that it has the potential to become a true game changer for biofabrication and regenerative medicine. When fabricating biological tissues with additive manufacturing techniques, we are facing a major challenge: time. With current 3D printing techniques, we are already able to print high resolution structures, but to achieve clinically-relevant sized constructs, printing times can be very long. With 3D volumetric printing, we were able to print 1 cm3 structures in 20 seconds. This makes a big difference, especially for the survival and functionality of the printed cells. Of course, there are still a lot of unanswered questions and plenty of options for optimisation. But with this project, we were the first to print living structures within a
You printed ears, bones, menisci… which tissue is your favorite?
(laughs) Well, I like the ear! This was the tissue that I focused on during my first research internship, so it’s kind of a soft spot for me. But in my PhD, I will focus on meniscus regeneration.
Will other organs be printable, too?
Yes, in theory all kinds of tissue are possible. I would think that soft tissues will advance more quickly, but at this point we can try a lot of things!
Have you been contacted already from other groups for collaborations?
Not yet, since the printer is in Switzerland. It would be great to bring one to RMCU and have more time to optimise the printing process for our materials and the cells. For now, we are only collaborating with the group from EPFL.
Who are not biologists, are they?
No, they are physicists in optics and photonics. Their technical skills go far beyond mine, so we definitely benefited a lot from their expertise and technology. From our side, we provided the biological and tissue engineering background that was needed to use this technique for bioprinting, so it was a win-win. It was a very nice collaboration where we all managed to learn a little bit of each other’s expertise. But more importantly, we were able to combine our knowledge for a very cool publication that hopefully paves the way for more collaborations.
So, after this publication, what’s next for the technology?
I think the next step is to look at the limitations we came across in this first paper, like improving the resolution and complexity of our printed constructs. Then, the idea is to dive more into the biology of our constructs, test different cell types, multimaterial printing, etc. There are many things we can try, since no one has tried them before, but I think it’s good to keep in mind that we do not have to do everything with only one machine. Our biofabrication facility offers plenty of possibilities. I’m excited to see how far the technology can go in the field of biofabrication!
I noticed that you are the only female author of your paper. Women in STEM are an often-discussed topic. How do you experience being a woman in a technical field?
Actually, with exception of one, all PhD candidates in our group are female, and I would say that we work in a pretty technical group! Among my female colleagues there are chemists, biologists, engineers, medical doctors and so on, so from my personal experience, gender has no influence on what each of us can do and choose to specialise in, it’s more about the topics and skills you enjoy and seek to develop.
At RMCU, we have state-of-the-art technologies, many different areas of expertise and an environment where you are encouraged to learn from each other. Personally, I am not very technically affine and have always had a stronger focus on biology. Knowing this, I have dedicated quite some time since my Master’s to learn more about this area. Now, I am able to work and optimise different printing techniques and have a better understanding of how they work. And when I run into trouble or get stuck, I can ask any one of our experts who has the necessary know-how. The diversity in technologies, expertise and people, that’s why I wanted to stay here after my Master’s. I could not think of a better place to learn and develop new skills!
Do you already have future plans for your career?
Not really, I don’t want to limit my options yet. Early in my Master’s, I told everyone that I was absolutely NOT going to pursue a PhD track, but here we are. If my PhD goes well and I continue to enjoy the work after 4 years, I will look into doing a postdoc for sure, but I am also attracted by industry. For now, I don’t say no to anything, only yes to opportunities. I am also running the Fundamentals of Biofabrication e-course since I like teaching, and we recently launched the Malda lab website. For now, I’m trying to learn and experience as much as I can about the different sides of academia.
Is there anything you would want to share with the RMU community? Any advice?
Collaborate! From my short time working as a researcher I’ve really come to value the advantages of collaborating and learning from each other. I think that when we try to do things by ourselves, we miss out on a lot of different perspectives and knowledge that is already out there. Get the support of experts and things become easier, faster and better.
Thank you, Paulina!
This blog is written by Katja Jansen (RMU communications officer (2019-2020) and PhD candidate in Drug Innovation (2016-2020)).