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Steakholder Meets: Discover 3D Bio-Printing

Discover 3D bio printing

Mor (host):

Hi everyone. Welcome. Let’s wait for everyone to join our speakers and our listeners. So let’s just wait a few moments.

I See Nadav has joined me as a speaker. We’re waiting for you as well, and we’ll get started. Until then, let me start by saying welcome to Steakholder meets our Biweekly Twitter space show that’s brought to you by Steakholder Foods. As always, my name is Mor Glotter Nov, and I’m the host of this episode. Today we’re going to discuss our 3D printing abilities. So for that, we have here our tissue engineering team leader, Dr. Nadav Noor and Moshiko Manor from the Engineering and Development Department. Hello to you both. And as I said, we’re going to talk about 3D printing, the perks of bioprinting, the challenges, and our very own unique value proposition. So I don’t know about you, but I’m really, really excited to dive into this topic because this is really our core values, and everything that we’re doing at the end of the day, tunnels into this. So if you’re feeling excited, just like me, stay tuned with us. If you’re joining us live, you can drop your questions as comments to our Q and A tweet. And we will leave some time for Q and A at the end of the show to answer any questions you might have. So, as always, let’s start with intros. Who wants to go first? Nadav?

Nadav:

Yeah, sure. So, hello everyone. I’m Dr. Nadav Noor. A little bit about myself. I did my bachelor’s degree in mathematics and computer science, but in my master’s degree, I decided to do some shift towards material science and engineering. And there it was when I first introduced to the field of bioprinting and tissue engineering, and it was so interesting that I continued to do my PhD also in the same field. My thesis was on 3D bioprinting of cardiac patches and hearts. It was under the supervision of Professor Tal Dvir. And once I finished my studies, I went straight to Steakholder Food. I joined it was two years ago as tissue engineering team leader. And I must say that it felt like a very smooth transition from in my studies when I printed the human hearts. Then I moved to Steakholder when I printed cow muscle and fat tissues. And maybe it sounds peculiar, but for me, it was very smooth and felt very natural, the transition.

Mor:

That’s about amazing. I’m super excited to hear more about everything that you’ve done until then. Moshiko, would you like to introduce yourself?

Moshiko:

Yeah, sure. Hi everyone. So I have a bachelor degree in electrical and computers engineering. And actually, since childhood, robotic systems have always fascinated me. Well, in my grown up life, I found 3D printers to fulfill this passion, the same passion that I had for robotics in my youth. So I’ve been working in the 3D printers industry since 2007 as a software engineer and as a system engineer at some times, which mean I have chance to develop machines and also to design new machines in the 3D printers area and united systems. It’s like more than a decade for now and I joined Steakholder almost two years ago and it feels wonderful.

Mor:

Amazing! You both are doing super interesting work. So let’s just go ahead and dive in with a few of my questions. And so I’ve done my research and I know that 3D printing has been around for a while now and just in recent year, 3D Bioprinting was kind of introduced. So let’s start with the basics. 3d printing.

Moshiko, can you tell me about where we started and where we are today, now in this field?

Moshiko:

Yeah, so 3D printing is basically like 2D printing, just accumulating each layer on top of the other one and creating a 3D object. It started to be commercial, I think, around the 1990s, at the early 1990s. And it mainly used for making fabrication for prototypes. And it was called rapid prototyping. That was the main issue with that. You can make with a single type of material with a limited resolution. You can create an object that you can hold in your hands. It didn’t take too long to make it. And you can check if it’s good enough, if it’s in the right dimensions, if you can use it to fit other parts in your whatever you were building, and then to decide if to move on to actual production. Well, with time, the print quality improved and options to print with more than one material was available. And we can actually print like, very sophisticated parts with some part of the object could be soft and some of it could be solid. And we could actually print models that we can use, not just as a prototype, actual as a product itself. And then there was a shift from rapid prototyping into additive manufacturing, which is actually like small scale batches that you wanted to fabricate something, but let’s say in thousands, not hundreds of thousands, and you can use it and do it pretty quickly. So we got a lot of materials today that we can print off. We got ceramics and we got metals, we got all kinds of glass and plastics, actually. And the printers options are even greater. You got very large scale printers and very high resolution printers, very small ones to like, microns resolution, to print all the details. And you can even print a bumper of a car in a single shot. So today is a long way from the start.

Mor:

That’s amazing. And so we’ve started, I guess, with 2D. Now we have layers for 3D. And you’re saying that we can print pretty much any material that we want at a very large scale and at a precise rate. So that’s amazing.

Moshiko:

That’s true.

Mor:

Okay, thank you. And so what is 3D Bioprinting and maybe why do we need it? This one, I think, is for you.

Nadav:

Yeah, thank you. So actually, instead of using the materials Moshiko mentioned, like metal, glass or ceramics, in bioprinting we use two main components, mainly cells and bioinks. And the goal is to print a tissue, not some solid object, but some biological object. In this, the cells are the functional units and the bioinks actually are the supporting materials which help maintain the cells viability and also support their ability to proliferate, to differentiate, and finally to mature. So in the printing process, we fit this mixture of cells and bioinks into the printer along with the model of the tissue that we want to print. And then the printer does its job layer by layer, as Moshiko said, forming this complex tissue. Here I must mention that we can form a very complex tissue depending on what kind of tissue we want. We can use many kinds of cells. We can use different bioinks, like, for example, a bioink for the muscle and a bioink for the fat tissue. Once we finish the print, we have the tissue almost ready. Usually there is another phase, which we call it the maturation stage. The idea is to give time for the tissue, for the printed tissue to grow and to mature and to give the cells time to start communicate with each other to form the functional tissue that we need. Maybe you can ask me, why do we need this bioprinting? What’s the motivation for it? This is started mainly for tissue engineering because we want to try somehow to simulate the native tissue. So we need some device that can help us deposit cells in a very accurate way to form these complex geometries, just like in our body. I mean, there’s very complex geometries in our body. I’ll give just one example, but there are many. I like this example of our blood vessels which are completely networking all of our body. Every cell in our body is in a maximum range of 150 microns from a blood vessel to get the oxygen and nutrients for it. So if we want to form the same tissue in the lab, we’re going to need to simulate this blood vessel somehow. So we need this device to deposit the blood vessel forming cells in this distance, in this resolution. So this is the 3D bioprinting. There’s of course, many other uses and examples, but for cultured meat, which is a very advanced and new idea, of course, because we don’t want to print a tissue that will be used for implantation or medicine. We want to print a tissue that we can eat. So we use it to place, to position the muscle and the fat in the right positions and with the right geometry along with the blood vessels, like tunnels.

Mor:

Okay, so correct me if I’m wrong for just a moment. We’re using the 3D printing to 3D biomaterials the bio ink and the cells. And then after they’re printed, if we want to keep cells viable, we need to keep them alive just like in the body with our blood vessels. So each cell needs to keep getting the nurture and nutrition in some way or another. Okay. And for cultured meat we’re using mainly muscle and fat.

Nadav:

That’s right. But again when we’re going to print very thick tissues again we’re going to need to somehow nurture the cells inside the core of the thick tissue. So we’re going to need to use the printing capabilities also to form these blood vessels like tunnels. Not only the fat and muscle of course.

Mor:

Okay, so I think you’ve touched a bit on this but so can you walk us through the exact stages before we actually start to print?

Nadav:

Sure. So I think we can divide the we kind of said it already but we can divide the printing process to three parts. The first part is to prepare the sales and the bioinks. The second is the printing process itself and the last one is the maturation stage. So I’m going to start a little bit about the first then I take it for Moshiko to do the printing process. So at first we need the cells and the bioinks to prepare that. We need very large amounts of bovine cells that we can differentiate to muscle and fat. And we need to use a very high concentration. So this is done in bioreactors. We grow them in growth media until we reach the required amount. Then we take and mix them with the bioinks which are usually plant based. That is because we don’t want to use any animal derived materials. So we mix it to the tech together we create this encapsulating bioinks of muscle and fat and then I give it to Moshiko to continue for me.

Mor:

Okay. Amazing. Take us through the next step.

Moshiko:

So I will get the bioink from Nadav and I will put it inside a special cartridge that will fit the machine that we’ll choose to print on either the industrial machine or the R&D machine which are different. After that someone will decide what kind of cut will you like to print, how many fat percentage will be in that cat. So once the model has been chosen it will be sliced within our software into layers like we said before and each layer is divided by the end to drops that we precisely drop on each and every one of our trays. So we can choose where to put the fat and where to put the muscle and if to do a bit of differences in the it’s not the viscosity, but we can choose how much fat and how much muscle will interact with one and each other by that. Just printing it and waiting to get to the mature part. So all the ink is traveling through the sterile machine and getting out of the nozzles onto the tray exactly like the model that the customer decided. So that’s the printing pot.

Mor:

I think in a few minutes we’re going to share the demo that we have where people can check out for themselves how they want to choose their cut of steak, whether they want a cereal or anything else, and what they want their percentage of fat to be. So you can kind of get the feel of what Mushika is talking about and try it for yourself. So we’re going to share that in the space in a few minutes. And so we want to print and we have everything that we decided on size, the fat ratio and everything else. And now we print what’s needed. Now, what’s the next step?

Nadav:

So I will continue from here, I think, a little bit more about the bioinks. It needs to be some kind of viscoelastic material. What do you mean by viscoelastic? It means that it changes its properties according to the pressure we are applying on it. Not linear, a good example for that. It’s ketchup, which is a shear thinning viscoelastic material. Once we press on the bottle of ketchup, the ketchup just squeezed out very easily. It flows through the nozzle of the bottle and after it reaches the plate, it actually accumulates very nicely and holds its structure. So this is very known viscoelastic material. Why do we want this kind of material? Because we want to be able to make the bowing flow through the entire tunnels, fitting tunnels of the printer. But once the drop exits the nozzle and reaches the printing plate, we want the drop to hold its structure. We can build this 3D structure. So this is very non material property. Hydrogels usually have this ability. So this is why we are mainly printing hydrogels usually. So once we finish the printing, we have the printout, the stake. We must move forward to the last stage, which is the maturation, which mean we have all the cells in the right position. But we need to give the cells now time and the right media for them to form the tissue that we want. We want the muscle cells to start shared in membrane and create these fibers, which is an amazing property to form these long fibers composed of thousands of cells. And they need time for that. So we’re going to move the printed tissue to the incubator and to the tunnels I discussed before. We will feed them with the right media for differentiation and once the fibers are ready, we can move it to eat it. Actually, that’s it.

Mor:

It sounds science fiction, I must say, but since I’ve been in the lab and I’ve seen the work you’ve all been doing, I believe you. Although it’s really insane. What about the environment that this is all done in? It needs to be controlled, right?

Nadav:

Moshiko, do you want to take it or should I?

Moshiko:

Yeah, actually, the printer itself, the first part of the bio ink that is making is obviously in a control environment in mind that the bioreactors and all the other stuff that he needs. Well, getting into our machine, it still needs to stay alive, all the cells. So the environment must be sterile and must be temperature controlled to expect that the cells won’t be hurt and can survive all the voyage. From the cartridges all to the trays and then back to the maturation stage. Does that answer your question?

Mor:

Perfect. That makes total sense to me. Thank you. So let’s talk about the technology. What technology do we use to produce the cuts of meat and why was this technology specifically chosen? What are the advantages of it? Who wants to take this one?

Nadav:

I’ll just start that. It’s like an anecdote. But in my studies when I printed the hearts, the human hearts, it was only a three centimeter size heart model and I used an extrusion printer with two printers and this printout took me about 4 hours to finish. And it’s only a three centimeter size heart. But this is of course it’s for medicine, it’s for implantation for for humans here we and we need some other technology for the food industry need to be something much with much higher throughput and different accuracy and different parameters. So Moshiko can elaborate on that.

Moshiko:

Yeah, so I think it’s a great example to see how much the application itself can change the way that you need to choose your machine. So you used the extruder and it took hours to make a small part and in our job is to make food for people, which you need to make tons of it each day. So obviously we cannot use that kind of method. So in our R&D lab we choose and we developed our own bioink drop on demand technology that is scalable and we can print in a small scale in our R&D lab or on our industrial machine, which is a very large scale. And then we can do it. And we can use our 3d printer abilities to do it precisely and repeatability and do it with sterile way that the cell will stay alive and the temperature won’t drop or won’t rise too much and we can choose where to put each one of the materials that we’ll need for the process to continue. So it’s a great example of the low throughput machine that you used in your lab. And actually we learned in our R&D lab how to print our bio ink in a small scale and it didn’t take much effort to make it scale up and to move on to the industrial printer. And that’s what we’re doing today. That machine can print tons of meat per day. I think it’s a lot.

Mor:

it’s exciting to see what the future holds. Yeah. What are still the challenges that need to be overcome in order to make 3D bioprinting a viable option with a widespread use?

Nadav:

So I think, in the tissue engineering part, because 3D printing is a tool for tissue engineering mainly. So it’s a challenge for the entire field, I think, how to mature thick tissues. And it’s two challenges together, I guess. One of them is how to continue to nurture the cells during the maturation phase, how to create these tunnels that will reach each and every cell and also exactly what media to use in order to allow the cells to maturate exactly to the tissue that we want. Because we try to somehow simulate our body or the cow’s body. So it’s a very hard thing to control in the lab. In the cultured meat space, I think the main challenge is how to do it cheaply, because maybe we can print a very nice steak and very tasty, but we need it to be cheap, also costly. And this is, of course, mainly the price of the media. But again, this is the challenge for the entire field. All challenges.

Mor:

Everyone wants to reach price parity. Okay. Thank you. Moshiko, anything else to add on that? I think he covered it all. Okay, so one last question before we take a few questions from our audience. So in your vision, what will the New Age butcher house look like?

Moshiko:

Actually, I never went into a butcher house because of my imagination of how would it look. But in the future, I think it would be in glass walls. Like, imagine yourself that everything is precise, everything is controlled, everything is under sterile conditions with no uncertainties about the process. That the food that we are making. So there is no problem for everybody to watch it. You know what I mean?

It makes it much simpler to bring it to the people. You can put it anywhere you want. It doesn’t have to be in some remote location far away, so nobody will know about it. It could be actually in the center of the city, really close to your supermarket, so you don’t need to waste any other energy to deliver the meat to the people. It will be much easier to control all of it. You could put it anywhere, which is amazing. Yeah, it’s a great.

Mor:

Really great vision. So let’s pause with this and let me see if we have any questions from our audience. Yeah, I see the first question here. Can this tech be built to scale globally? Who wants to take this?

Moshiko:

Yeah, if I understand your question is, can we spread it anywhere we want? Our machines could be anywhere.

You’ll need your biological lab to grow the cells, and you need your machines somewhere, and you can print it. You don’t need to travel or take ships or airplanes and to move things around. You’ll do it locally and much better. Yeah, but also at scale. Yeah, scale.

Nadav:

I must mention that it won’t be like a small in house for every home printer we are talking about. It’s more like a factory,

Moshiko:

But it can be everywhere. Yeah, it is small enough to hold it in each city. So you don’t need to transport what you’re making all around the world. You can make it locally, really close to your people. Exactly. I think

Mor:

It’s something that will definitely facilitate food security issues that it seems that we’re going to struggle with in the future in our planet. So definitely. Interesting question. Another question that I see here. I’m going to rephrase it a bit, but in the future, is it an option, and will 3D printing be capable of printing bone in meat cuts like a T bone steak? Potentially?

Nadav:

Yeah, sure. Of course. This is just another kind of tissue that you need to learn how to grow the right cells and the right maturation that they need. But potentially, yeah, any kind of tissue we can do. We have now the cells that are capable of differentiate to every lineage, so there is no issue.

Mor:

Interesting. And then how long does it typically take to 3D bioprint? A specific structure, just like steak or fish?

Moshiko:

It depends on the machine that you are working on. If we’re taking, for example, our R&D printer, it will take a few minutes, but on the industrial machine, it will take a few seconds. So it depends.

Mor:

Yeah. Okay. And then are there alternatives to creating 3D biostructures?

Nadav:

Yeah, there’s many methods, tissue engineering methods to create biostructures. Some of them are more simple than bioprinting. Let’s say the simplest one is molding. You can just cast the biomaterial to a mold and form the tissue. But again, it’s very simple. But again, the product that you get is very simple. Also, there’s no complex geometries. You can use only one kind of cell. There are also other methods. I won’t go into them, but like freeze drying of sponges, create some sponges which are very porous. This can help solve the problem of the nutrients diffusion through the tissue. There’s also a very nice method of spinning, electrospinning or red spinning, creating very nice fibers. This is very good if you want to engineer muscle tissue, but it’s usually used mainly for very thin tissues. It’s very hard to create a thick steak using this method. So there are many tissue engineering tools. But I think that, again, the advantage of bioprinting is the accuracy, the complex tissue you can get, you can use many different cells and bioinks, and of course, the prototyping. You can just model very fast whatever you want and print it.

Mor:

Yeah. Okay, that’s it. I think we don’t have any more questions. So, Moshiko and Nadav, it was really a pleasure speaking with you today. Is there anything else you want to share before I wrap this space up?

No, we had a great time. Thank you.

Mor:

Okay, so great. Thank you both. And thank you, everyone for tuning in. Don’t forget to join us in two weeks for our next space. We will announce a topic and speakers in the next few days, so make sure to follow us for updates. And you can find all the previous episodes on our website and on our YouTube channel. So have a great day, everyone.

Nadav:

Thanks. Bye.

Moshiko:

Thank you. Bye.

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