About this Interview
Check out this informative interview between Dr. Mayasari Lim (Roosterbio/3DHEALS) and Adam Feinberg, Professor at Carnegie Mellon University, CTO and co-founder at FluidForm. Learn how Adam first got into 3D printing and bioprinting (years ago!), and how his team at CMU discovered the FRESH technique. Adam also shared his view on how to stay critical of convention and learn to think outside of the box. Adam will be speaking at the Organogenesis/Bioprinting panel at 3DHEALS2020 in June 2020.
What inspired you to start your journey bio-fabrication/bio-printing?
Yes, I have been interested in 3D printing for a very long time. When I was a co-op student at Cornell, I did a co-op at Abiomed in the Boston area, working on total artificial hearts and at the time, rapid prototyping was used to make these mocks-up (in the late 90s) all in SLA but the resins were all phototoxic. I was enthralled by the idea of why can’t we just use this to build medical device directly, and why did we have to use this only to prototype and then as we moved to a device we need to test, we had to cast, machine it or mold it.
So, it was really clear what the potential was. Since then, 3D printing has also evolved from rapid prototyping to additive manufacturing entirely because the materials we were using and the systems in some degree have now progressed to the point where we can use what comes off the machine.
So since I was 20 years old, I have been fascinated by this technology. I started my lab in 2010 at Carnegie Mellon, this is when MakerBot appeared, FDM patent expired, the RepRap community started to grow and MakerBot is the company that really brought this to my attention. The first 3D printer we had was a Cupcake which is made out of laser cut wood in the lab, someone made a horrible extruder, perhaps not so at the time, but it was really poor that could just spit out a paste.
We were intrigued by the idea – we know we want to be able to additively manufacture some of the stuff, these technologies are becoming cheap and we had a Fab at Home, a project from Cornell at the time. I started the project at the time because EnvisionTec bioprinters at the time was $200,000 which at the time, I did not have. The idea of how we can bootstrap and the great thing about CMU is that we have engineering students everywhere.
So when I pitched the idea to students, they were ready to roll up their sleeves and get into it at CMU. Unlike many labs, we have been in this open-source bioprinter platform. All our publications have been based on open-source designs, mostly desktop grade FDM printers that we modified with custom extruders and turn them into bioprinters, that has been what we have used ever since. To me, it is exciting that we have been able to publish the paper last year in Science on a printer that we built under $1000, (I kinda like that).
There is so much innovation still in the space. If you can identify the problem that needs to be solve, very often it is the creativity and ingenuity that gets us the solutions and step changes, not necessarily a giant pile of cash. At least from an academic standpoint, and now we are trying to transition some of this work into a commercialized product in the bioprinting field, which is still very nascent compared to the rest of additive manufacturing which is a lot more mature.
FRESH printing technique – how did you come up with this idea?
This was a project that was driven by my Masters then Ph.D. student, TJ Hinton. I challenged him to print hydrogels, there was not a great way to print at the time, they are soft and cannot support their own weight. We were kicking around different ideas and he had an epiphany about using gelatin microparticle support. For those who are not familiar, we basically print inside a gel, like a hair-gel material, we extrude inside of this material and whatever gets extruded directly into it, gets stuck in place. The reason the support bath we use is made of gelatin is that we can print at room temperature and then we just raise to body temperature so that the gelatin can melt away without destroying any parts of it.
He started this out with buying a packet of gelatin that you buy from the grocery store for baking which has a really rough powder. He basically put it into a dish, made it into a slurry, and printed into it and it kinda works. At first, when he showed it to me, he wasn’t too excited about it but when I saw it, I got super excited because I knew that we can fix the particles but this basic idea is going to work. That was probably 2012. We had our first paper in 2015 and another one last year and started our company in 2018. For a relatively simple idea to transition into commercialization, it is not a quick transition for sure.
Tell me more about your startup FluidForm – what is your vision?
Fluidform is focused on what FRESH enables, which is 3D printing of liquid materials. That is the unique thing that what we bring into the marketplace, by printing into this gel environment we can print a wide variety of fluids, some might gel and solidify right away, some might take days to cure. For example, you can print a silicon that you might normally mold but it will stay in a liquid shape for days until it adheres if that’s what you want. The vision of the company right now is focused on what we do best, which is in bioprinting of collagens and other hydrogels.
We are looking at this in 2 different ways – (1) the research market, which today there are already a lot of research grade bioprinters like Cellink and Allevi, and EnvisionTec, Regenhu and Advanced Solutions. We are looking to support all of the existing printers with our FRESH support materials, essentially to make them work better. Almost any extrusion based printer is compatible with FRESH so if you go to Allevi’s or Cellink’s website, you will find LifeSupport. We also sell through Advanced BioMatrix, LifeSupport works really great with LifeInk, a bioink we use in our Science paper.
We do this because we hope that the research today is going to be applications for tomorrow. A lot of the tissue engineering and RM application are still early. Maybe they are in early clinical trial stage, but most are in animal studies but what we want to do is support that and hopefully provide better results with FRESH and people will become more successful. From a company’s standpoint we are hoping to look at other markets as well, and other areas of printing of collagen is of high value.
For example, in the area of tissue modeling and surgical planning, people are familiar with making models out of plastics from an MRI or CT scan. We are also making this out of a rubber like materials to give it a tissue feel but if we are print collagen then we can actually printing something that has the exact tissue feel. We see this as a potential interesting market, it’s not exactly TE or RM but it is using our core technology that can be used today. Also without worrying about regulatory challenges.
Can you share some of your early successes and failures in your work that change how you approach your work/research today?
Success/failure, to me, is part of the same thing. Research is really about learning from your failures and figuring out what the right path and success look like. In our Science paper, we had this 3D printed ventricle, and for the longest time, we thought that you have to mix the cells with your hydrogel bioinks cos that’s how everyone “bioprints” and that was really not giving us good results. Eventually, after hitting our heads against the wall many times, but we took a step back and looked at real tissue. For example, if you looked at muscle tissue, how it is organized? It has high-density collagen that makes fascia and other kinds of no-cell, just ECM that helps to organize muscle fibers. And muscles are just all cells, at very high concentrations, 1-2 orders of magnitude greater than what most people bioprint with.
So, we took that strategy and printed collagen by itself to define tissue compartments and changed our cell inks to 200-500,000 cells /mL (very high) and by doing that, we were finally able to get muscle constructs that we can print, function and beat. What was interesting is that this whole time we had MRI images thinking that we were mimicking nature, but we really were not, cos nature is not low cellular density hydrogels. We now applied this to a number of other tissue systems, not published yet but pretty robust as this is how most tissues are put together.
My advice to people is that, just because you read 50 papers and they are all doing it in a certain way, don’t think that’s the way it has to be done. There is so much space to innovate, we don’t yet know the answers, we are dealing with best guesses, we are trying things out, testing hypothesis. Sometimes it’s these little things that “let’s just do it this way” and then you realize that that does work, and then the next generation of things build on and it will hit the next roadblock and so on. Hopefully, that’s good advice!
Professor Adam Feinberg is CTO and co-founder of FluidForm. The core technology of FRESH printing was developed in his Regenerative Biomaterials and Therapeutics lab at Carnegie Mellon University (CMU), where he is a Professor in the Departments of Biomedical Engineering and Materials Science and Engineering. His group develops materials-based, engineering strategies to control the self-organization and assembly of various cell types into tissues. Adam earned his Bachelor of Science in Materials Science and Engineering from Cornell University, and his MS and PhD in Biomedical Engineering from the University of Florida. He performed his postdoctoral work at the School of Engineering and Applied Science at Harvard University. He holds more than 20 US patents and patent applications, has authored over 45 publications, and is a member of the Materials Research Society, American Chemical Society, Society for Biomaterials, Biophysical Society, Biomedical Engineering Society, and the American Heart Association.