Episode #89 | The Bioprinting Frontier (Live Recording)

The future of medicine is growing closer to recreating the very building blocks of life itself. In this groundbreaking discussion, four bioprinting experts reveal how their technologies are moving rapidly from laboratory concepts to clinical realities that could forever change how we treat disease.

Mike Graffeo, the CEO and co-founder of FluidForm Bio, shares the group's remarkable progress toward eliminating insulin injections for type 1 diabetes patients. Their FRESH 3D bioprinting technology creates implants that produce insulin naturally in response to blood glucose. "Life should not come with a needle," Graffeo emphasizes, highlighting how their approach could deliver a functional cure. 

Other leaders in bioprinting go on to share their unqiue approaches to 3D innovation in medicine. Annaliese Vojnich, Business Development and Technical Sales Manager at ViscoTec America, demonstrates how Puredyne's progressive cavity pump technology achieves precise extrusion while maintaining cell viability.

 Dr. Jorge Madrid-Wolff, Application Scientist, reveals Readily3D's volumetric printing, which creates complex structures in seconds rather than hours, enabling functional mammary gland models that produce milk proteins and beating cardiac tissue. Dr. Karolina Valente, Founder and CEO, explains how VoxCell BioInnovation's vascularized tissue models are addressing the 95% failure rate of oncology drugs in clinical trials by providing more translatable data than animal testing.

Ready to witness firsthand how bioprinting is transforming from science fiction into medical reality? This discussion provides both the scientific foundations and practical pathways that will bring these revolutionary technologies from laboratory benches to hospital bedsides within the next decade.

Sound Engineer: Faith Fernandes

Event On-Demand

Chapters

• 0:00 Introduction to Bioprinting
• 3:46 Mike Graffeo: FluidForm's Type 1 Diabetes Solution
• 25:53 Annaliese Vojnich: Puredyne by ViscoTec for Bioprinting
• 40:16 Dr. Jorge Madrid-Wolff: Readily3D's Volumetric Bioprinting
• 1:01:09 Dr. Karolina Valente: VoxCell BioInnovation's Vascularized Tissue Models
• 1:21:43 Panel Discussion: Form vs. Function and Future Outlook
• 1:35:01 Q&A and Closing Remarks

Transcript

Speaker 1: 0:00

Well, good morning everybody. Thanks for joining us. We accidentally clicked the button a little bit early, so you stared at the blank screen a little bit. I apologize for that. My name is Jenny Chen, ceo and founder of 3D Heels, a small company but hopefully to make a big difference in the space of healthcare, 3d printing and bioprinting.

Speaker 1: 0:39

And three missions for us is one is education. This is one activity we do, different from in-person events when it comes to networking, but I think now we're five years in. I think we have acquired an amazing set of skills to engage our audience, and the audience also know how to use these opportunities to learn and network with one another. So some of my suggestions to network is one say hi in chat so that we know you're here and actually engaging with us, and your social links. If you want us to follow you, uh, or connect with you on linkedin or instagram or whatever that you use um and and, yeah, and ask questions, uh, in terms of questions, please put them in the qa box, because I am a one woman show here. I don't have more than two arms, so and just one brain, so please help me out here. And and chat, you know, and then advise, give people advice and engage. And also, if the speaker is doing a great job, react. Use the react button on the bottom. They will love it and and that's it.

Speaker 1: 1:45

And then number three mission for us is a program called Pitch3D. It's a free fundraising program that we created since 2018, where we give startup opportunities to present themselves to a group of institutional investors. We have corporate and regular VCs and also angel groups. So if you're an early stage startup founder, connect with me and then see if you're a good fit for the program. Okay, without further ado, I think today's topic is quite important and it has been a founding subject for our group is when can we create artificial organ or tissue or things that are even remotely close? Because for decades we are not even close. This industry is that it's getting closer and closer every year, or maybe even every day, I would say.

Speaker 1: 2:46

In this space is how we can use the science of bioprinting, biofabrication, regenerative medicine to change the future of medicine, and so, without further ado, I'd like to introduce our first speaker, mike Grafew. I know Mike for many years now actually since 2018, and he is a highly accomplished individual. He is a CEO and co-founder of Fluidform Bio. You see the logo in the back. But he also basically helped four novel medical device or therapeutics through FDA and he has generated total sales of $20 billion altogether. That is just an amazing figure. He's also an engineer by training and a business person combined, and also a Baker Scholar I just read about it which is a very high honor for Harvard Business School. So, mike, with that intro, please take over.

Speaker 2: 3:47

Thanks, jenny. I appreciate the kind words. It is hard to imagine that it was seven years ago when we first met, when 3D Heels was getting off the ground and so was Fluid Form Bio, and we've come a long way and I'm excited to share some of the progress. It's a real delight to be able to share the stage with so many accomplished speakers. I'm really looking forward to the other presentations as well, and I think you know it's really timely right now to talk about this where the promise of you know, hey, we're all going to have tissues and organs. I remember hearing that for the first time in 1997, reading Joe Vacanti and Bob Langer's papers and getting really excited about this whole term of tissue engineering as a field. This is a topic that's been near and dear to me for some time and I'm excited to share with you what we're doing at Fluidform to advance this forward. I think this is one of many really exciting efforts out there in the world and I do believe that you know that we've actually now taken a big step forward in the field to move away from promises and someday maybe out to actually really making these things happen and possible. So I'm gonna pull up some slides to share a little bit about what we're doing here at Fluidform, and let me just make sure that's the right window. Hold on, yeah, that should work and we will go into a full presentation and I'll walk you through a little bit about what we're doing here. So at Fluidform Bio, which was founded in 2018, I founded that company, co-founded that with my co-founders at a Carnegie Mellon based on some really exciting technology that I'll walk you through, and we are using that technology today.

Speaker 2: 5:27

Our first indication is focused on treatment of type one diabetes. Our goal is to eliminate the need for insulin injections. We believe that there's a really important need here. My prior experience before working with, before co-founding this company was with an insulin pump company for patients with type 1. And so I know the situation really well. It is by far the best time in history to live with type 1 diabetes, given the tools that we have available wearable insulin pumps, continuous glucose meters these are all tools that make the management of the disease much, much easier, and it's still a disease that you have to think about almost all day, every day, and we just believe that life should not come with a needle. You know, you really do have an opportunity here to make an enormous difference. It's actually a field that's been studied for over 40 years and for the better part of the last 20, there's been a really interesting paradigm where we know that transplantation of islet cells the cells that produce insulin in response to blood glucose we know that that can work. We know that you can create insulin production by transplanting the right kinds of cells.

Speaker 2: 6:39

There have been a few challenges. One of those challenges was we were relying on deceased donor supply of the cells, and that challenge has largely been lifted over the last 20 years with the advent of induced pluripotent stem cell work to create differentiation protocols. There's now a number of them and by and large there are multiple ways to get access to effectively an unlimited number of high quality cells. But we still struggle with the need for systemic immune suppression to prevent immune attack. We struggle from the need to implant inside of vital tissue organs Think about things like the liver or the kidney in order to expose the cells to enough blood supply, and if we don't implant in those structures, we struggle with a lot of cell death because the blood supply is limited. The pancreatic islet cells require an enormous amount of blood supply, so our belief is that these cell therapies will be a cure for type 1 diabetes and we need to solve all three of these. We've taken a look at this and said listen, there's some really large names and some very big brands on this slide, some of the biggest biopharma companies in the world all working on these solutions, and many of them have pieces of the puzzle that are looking really promising. We believe that you've got to put all of it together. You've got to avoid systemic immune suppression. You can't implant inside of liver or kidney or other vital tissue and you need to be able to rapidly vascularize to avoid this cell death, and so we've created an approach that allows us to implant easily right underneath the skin. It can be removed very quickly, very easily if it's needed. There's no need for any systemic immune suppression and there's an ample blood supply that's enabled by our technology.

Speaker 2: 8:23

I'll talk a little bit about what that means and why we think that this represents sort of a novel way of thinking about this, by providing that blood supply in the subcutaneous space, making this ecosystem possible, and that's really enabled by our core technology. We call it fresh 3D bioprinting. I'll talk about how it works, and it allows us to make an implant that looks something like this cartoon, a schematic. There's really three ingredients inside of there. The ingredients start with the beta cells themselves, the cells that make insulin, and we surround them with the right kinds of extracellular matrix proteins that they're accustomed to being surrounded by when they're actually inside of a native pancreas. The third ingredient is a depot of a locally acting immunosuppressant, so that allows us to control the immune response just right inside of that area without causing all of the side effects of systemic immune suppression. By putting that into the subcutaneous space and by manufacturing it using our technology, we see a very, very rapid infiltration of blood vessels into that structure, and that's the key that really unlocks the possibilities here, because we can get blood supply to these cells quickly. They can engraft, they can survive, they can thrive and they can function for a really long time.

Speaker 2: 9:40

So how do we do that? Well, fresh 3D bioprinting sounds and looks an awful lot like some other bioprinting technologies out there where we deposit cells and proteins out of the tip of a needle in a spatial pattern. What's really different is we do that inside of an aqueous environment. This aqueous environment has certain special properties that allow cells and proteins to both go through their native self-assembly mechanisms inside of that gel. But that gel is then quickly washed away and you're left with a self-assembled piece of tissue that consists of just the cells and proteins and growth factors that we pattern in there. We don't need to add other kind of biomaterials or structural elements or members in order to create something that is biologic-like. We're actually able to really recreate the fundamental biologic properties of tissues, and I'll give you a quick video of what that looks like here, so you can see out of the tip of a needle here.

Speaker 2: 10:35

This is an example of a densely laden cell bio-ink being printed into a particular pattern. Once that gel is released, you can see that what's left behind is really just a densely cellular tissue. And that's one of the real advantages of doing this technique is we're able to work. We're able to build cellular scaffolds, but not doing it by building a scaffold and then adding cells. We can add cells that are extremely densely packed right into the quote unquote scaffold, exactly the way that we want to.

Speaker 2: 11:07

The other thing that's really exciting about this is, because of the properties that we control inside of that bath, we're able to give rise to a very, very rapidly vascularizing implant. So what you're looking at on this slide is an example of two materials of either collagen materials that were implanted underneath the skin of a mouse, one was conventionally manufactured on the left, the other, on the right, was manufactured using our bioprinting technology. Otherwise they're identical the same materials, the same concentrations implanted for the same duration. You can see really quickly one of them looks a lot redder than the other. That's because it has a lot more blood vessels and when we look at it under a microscope, we see extensive vessel network formation all the way down to the capillary scale. This is just under 10 days of implant and this was published in Science back in 2019. I'll show you a quick fly through video of that, where you can see just throughout the implant. I'll show you a quick fly-through video of that, where you can see just throughout the implant blood vessels everywhere.

Speaker 2: 12:07

That ability to stimulate that blood vessel formation is one of the really exciting things about our technology how it works and what we're able to do with it. And it was on the back of seeing that data that my co-founder, adam Feinberg, in his lab at Carnegie Mellon, started to collaborate with folks at what was then called the JDRF. It's now called Breakthrough T1D. It's the premier research funding institute for type one diabetes in the world and they were able to first demonstrate some promise in this technology in terms of being able to vascularize the islet cells that we see in an implant. They did that in the lab and the company about a year and a half ago almost two years ago now. We picked up that work and started moving it towards translation, and so now I'll share with you some of the data that we see about why we're so excited about what we're doing.

Speaker 2: 12:53

This is an example of a scaffold that was built with human islet cells and implanted into a mouse, and I'll point out a couple of things that are really interesting and really different here. No-transcript, robust cell health here at day 97. The other thing that I'll point out that's so unique and unusual here is what we're not seeing, and that's sort of a, you know, the hallmark response that we see in most of this field is a fibrotic response that you see to any of the synthetic kind of biomaterials. You'll tend to see a walling off or a macrophage response. You see this sort of a highly high fibrosis environment and that's been a real challenge for the field for most of the last 15 or 20 years. When looking at encapsulation technologies, we don't see any evidence of that, and we think that's largely because the materials that we're using don't elicit that response and we have a lot of data supporting that and the way that we build it really promotes that sort of integration as opposed to that sort of isolation.

Speaker 2: 14:19

The other thing that we're really excited about is our data on actual implants in a diabetes model. So what you're looking at here is an example of a study that we've done where we take a mouse, we give them an injection that induces diabetes. We see a very rapid rise in blood sugar, way up above the normal threshold, and then at day zero we implant our scaffold and you can see that blue line there. The blood sugar levels come down quite rapidly and then they stay down and stay really level and steady over the course of a six-month study. This is really exciting for us because when we compare that to the control, where we inject the exact same number of islets in the exact same location with the exact same extracellular matrix components around it, but we don't build that into a construct using our technology we see no blood glucose reduction at all, and so this is an area where we know that it's really our technology that's driving this response and driving the blood vessel infiltration that's allowing the cells to be healthy and do their job. This six-month data is the data that we're really excited about. It's part of why we're able now to be out and actually raising more money to expand the studies into larger animals and really move towards human translation. The other thing that we've shown in this same study is that when we take our scaffold out, we see a very rapid return to that hyperglycemic state high blood sugar levels. We know because we implant human cells into the mouse. We know we can measure for the human cell levels, so the human C-peptide and we see no human C-peptide after we retrieve the scaffold. So we know we get a full scaffold retrieval and we see that hyperglycemic state. So we know that it was due to the scaffold, that we see that blood sugar control and we know that we can retrieve the scaffold effectively.

Speaker 2: 16:09

The other thing I'll just point out is we've also developed some really exciting data on local control of the immune system. So what you're looking at here are these are nude mice with an immune system, and so we're able to actually image, using a special kind of camera, reporter cell lines that actually light up using RFP, and in the negative control you can see at day zero there's these nice bright spots there. Those are the cells that were implanted and then by day 28, we basically see nothing, whereas with some of the immune controlling agents we can see that at day zero and at day 28, we still see a strong signal. So we know we're having an immune protective effect. We're now doing a number of other studies, both around dosing and different agents, in order to demonstrate what the best kind of cocktail is and how we want to dose that in order to achieve the maximum level of control. But we know that we can do this for a really protracted period of time and that's part of what we're going to be building out for our pathway to the clinic.

Speaker 2: 17:08

I'll also just mention that you know we're also working with the folks at Breakthrough T1D. We did just sign an industry discovery and development partnership with them and we're super excited to start that work. We're thrilled that they're as excited about the work that we're doing as we are. As I mentioned earlier, they're really, you know, an outstanding group in the field and we're particularly excited about, you know, moving forward and working in collaboration with folks who've been, you know, dedicated their life and their mission to helping to solve for this. So, you know, with that I'll just, I'll stop the share of the slides and just sort of leave, you know, my final thought, which is that, you know, this field is incredibly exciting and I talk to engineers and scientists every day who say to me Mike, I've been excited about tissue engineering for 5, 10, 15, 20 years and there, you know, there just haven't been that many things over the course of the last several that actually look like they've got a chance to make a difference for patients' lives.

Speaker 2: 18:10

And so, you know, we're really, really excited about the work that we're doing, in large part because this is something that has translational relevance, that is going to help patients, that we believe has a very clear pathway to get into the clinic, and that's part of why we're so excited. You know, from a company perspective, we are raising our Series A right now. We have a lead investor and we're building the syndicate in order to close that shortly. And so for us, it's really about doing the science, it's about getting the data and it's about making that progress to get into the clinic. I'll leave it there and happy to answer any questions now or at the tail end the tail end.

Speaker 1: 18:46

Thank you, mike. That was a fantastic presentation. Really excited about the progress Fluidform has made so far. Also interesting I was just looking it up. By the way, I want to mention that Mike and I we did an incredible podcast. I'm going to share the link and, for people who want to dig deeper about what Fluidform is doing, that's a good resource is doing, you know that's a good resource and also, you know we're 2025, we're approximately 100 years away from the discovery of insulin and establishment of this kind of almost kind of like the beginning of tissue engineering to cure diabetes. And in fact, back then, if you have diabetes one, that's a death sentence. No question, it is a miserable death. So, where we are today, it's really exciting that we're almost going to get a cure. That's amazing and plus type 1, honestly, if you have a really bad type 2, is eventually you're going to need insulin injection. Potentially, you know that could be open as an option for type two as well, isn't it?

Speaker 2: 19:49

I would think so. Yeah, you know there's a point in time in severe type two where you end up with really intensive insulin management, you know when you move beyond just a long acting or a basal insulin, and you know I would imagine that something like this could help those patients a lot.

Speaker 1: 20:06

Yeah, awesome. We have a couple of questions from the audience. One is from Bill Harley. Hey, mike, great talk. What are the key features of the special spatial arrangement process that is helping to reduce fibrosis? In addition to more compatible material properties themselves, in addition to more compatible?

Speaker 2: 20:24

material properties themselves. Yeah, bill, it's a great question. You know, when we look at the spatial arrangement, we're looking at a couple of key things, you know. Number one we want to build the scaffold in such a way that there is a particular kind of surface patterning that allows for the attachment of the host blood vessels to sort of attach and infiltrate, right. And so when we're thinking about the materials that we're using and how we're building that patterning, that has to do with the density.

Speaker 2: 20:54

It's the ECM proteins that largely give those sites for the blood vessels to first sort of attach and start to infiltrate. And so we're thinking about the density of those and the materials that are used in those as well, as you know how close below that the cell level starts. So we want to give sort of an outer coating associated with those proteins and then we want to get the cells really close to the surface spatial patterning elements. The other thing I'll just mention is you're absolutely right, it's the biochemistry is the most important part, right? So the fact that we can promote this sort of native assembly of collagen in this aqueous environment where we print is the feature that allows that sort of presentation that the blood vessels love to grow into, as well as the sort of micro porosity that we can control with the aqueous bath itself.

Speaker 1: 21:44

Okay, that's a very thorough answer. Now, next question from Randy what are the cell density within the gel that you're printing? That's kind of continuing of what you just talked about.

Speaker 2: 21:55

Yeah, so, randy, we have data on printing well north of 300 million cells per ml, basically thinking about printing at the density of a cell pellet cells per ml, basically thinking about printing at the density of a cell pellet. In the islet cell program we've printed up not quite that high but pretty close to it and we're able to work with really, really high cell densities. As far as I know, we're able to work at least 2 to 3x higher than most of the rest of the field as far as cell density goes.

Speaker 1: 22:22

And another question how many extruders do you need in order to produce scaffold and vascularization network with this method?

Speaker 2: 22:31

Well, what we've printed with to date, we've worked with as few as two and we've worked with as many as four or five. We have a system that we've built and optimized in-house that allows us to do that with a really, really high level of repeatability and reproducibility. But by and large, you know, two has been enough for all of the small animal studies, and we are always looking at how do we optimize that. You know it's a balance between how many different compositions you really want to incorporate and what it's going to do in terms of time for the print different compositions you really want to incorporate and what it's going to do in terms of time for the print.

Speaker 1: 23:06

And just a quick question about the density and extruder. I mean, my question is when you have such a high density, I mean, do you have to overcome some challenges of cell viability issues?

Speaker 2: 23:17

Yeah, you know we're really fortunate, right? My co-founders have been working with hundreds of millions of cells per ML for gosh close to a decade now. So yes, we've developed a lot of tips and tricks on how to make that work and, by and large, a lot of it is because of the fact that it's fresh. I don't think a lot of what we do would work outside of a fresh 3d printing environment.

Speaker 1: 23:43

Excellent. Well, thank you very much, mike. We will come back to you at the end of the webinar for our panel discussion, but I will introduce our next speaker, annalise. Annalise Votnich I always have a hard time pronouncing her last name. I hope I didn't butcher it this time. Annalise, are you online? Okay, I think she has some computer issues. Oh, are you fixed?

Speaker 3: 24:18

your computer issue. Yes, if you can hear me. Sorry, it just took a minute to unmute.

Speaker 1: 24:23

Oh right, we have a 1980s computer right now running in the background. Sorry, I think it's just super full. So a quick intro about Annalie. She currently is the business development manager for Visco Tech America and she is combining science, technology, entrepreneurship all in one to promote this incredible device behind her, annalise, I'll let you take away.

Speaker 3: 24:52

Yes, Thank you, Jenny. Let me quickly just share my screen. Hopefully it will be quick with no problems. Let me know if you can see this or if there's any issues.

Speaker 1: 25:10

Let's give it one minute.

Speaker 3: 25:13

I apologize everyone.

Speaker 1: 25:18

It looks good. At least it's working.

Speaker 3: 25:21

I should be able to get it into presentation mode here in one second. Sorry about that, okay, just a little slow.

Speaker 1: 25:31

Well, you know when. I started to use computer. This is actually quite quick. Okay, Change the display setting.

Speaker 3: 25:39

Okay, sorry about this One more. And how are we looking now?

Speaker 1: 25:49

Give it a minute.

Speaker 3: 25:50

Oh, there you go, perfect, okay, uh, my apologies everyone. Um, yes, thank you, jenny, for the introduction. So, as jenny mentioned, uh, my name is annalise and I am the business development and technical sales manager at Fisco Tech. I've been here for roughly three years supporting all of our bioprinting and hygienic manufacturing. So today I'm going to discuss our paradigm technology, where it fits into the frontier of bioprinting, and share some key examples of our technology and where we have applications. So today I mentioned the agenda. I'll start with a quick introduction to ViscoTech. We'll walk through some core challenges that we've seen in the market, and then I'll also explain how Paradine's progressive cavity pump technology, along with our temperature control solutions, can directly assess these challenges. And then, lastly, we'll look at real world applications and what's next in terms of Paradine. So who is BiscoTech and Paradyridine and what do we do? So we are a German-based machine manufacturer utilizing the progressive cavity pump technology, so we focus on all these different areas you can see on the left side of my screen for advanced fluid handling and for dosing solutions. In all of these industries, we focus on difficult to handle materials, whether that be low viscosity and high viscosity, abrasive, solid filled, and also one part and two part materials. So one part and two part materials. Paradine by ViscoTech is a product brand that's specialized specifically for the bioprinting market. As you can see on our map here, we have a global presence. I myself am located in Atlanta, but we support the globe and have local support and expertise wherever it's needed. Current gaps in the bioprinting space. So before we created and developed the Paradigm system, we looked closely at the market and we found common issues such as inconsistent extrusion, nozzle clogging, failed prints, and therefore we developed our system to specifically combat these challenges so that the researchers can focus on their research and their prints instead of the actual bioprinter itself.

Speaker 3: 28:51

So what is Pyridine? Essentially, it is a single-use design system extrusion-based bioprinting technology utilizing the progressive cavity. So on the left side you can see what we've done is built our progressive cavity technology into a disposable barrel syringe, and then we have a pump system that's driven by a stepper motor where you can load your material, attach the cap, print and then dispose, and this helps to avoid any cross-contamination or anything like that. And then on the right side, we also offer an optimal process control utilized with our temperature control technology device, and here you just insert the pyridine into the slot as shown and run your prints the same way, and here we can keep the temperature controlled from four to 40 degrees, depending on, maybe, what the cells need or what the researchers need. I'll play this video. Hopefully it is loading for you all. It utilizes the progressive cavity technology shown here, so you can see it enables low shear volumetric extrusion, which is crucial for cell viability, and then we also are able to deliver 99% dosing accuracy with clean start and stop endpoints of each print. We're also able to run the rotor the white part in the video in reverse direction to perform a suck back to help eliminate the nozzle clogging and make sure that the prints can be very defined. Sorry, I just wanna make sure my screen is loading here from the video. Okay, enabling the future. So innovations where we have bridged the gap in the market, where we saw the needs, and developing our pyridine system. So this table highlights the key challenges that we've identified and how we have solved them extrusion and cell damaging, shear stress to limited bioink compatibilities and temperature sensitivity. We have engineered solutions for each challenge. With our progressive cavity pump, our broad viscosity range in terms of the bioink materials and our optional temperature control, we offer a complete, reliable process for modern bioprinting needs.

Speaker 3: 31:51

Next I'll show you some examples of biomaterials where we've successfully printed in our labs using our system or also with our partners or collaborators in different research facilities. So with the Pyridine system we're able to print all different types of hydrogels. Our systems are often used by researchers that are looking at cell function and cell viability in terms of prints. On the left side you can see we've printed here with gelatin material so we've able to print layer by layer and height on different constructs. The next one is gonna be a pleuronic F127 that we've printed with Sorry about that. And then you can see the ear picture here. So we have printed this ear design with a blend of alginate and cellulose with cell links material. And then on the far right you can see this is a bone material print. So despite the high viscosities and the particle counts, we're still able to achieve excellent precision in terms of prints here, which is a key advantage of our progressive cavity problem.

Speaker 3: 33:27

Cavity problem Our goal at Pyridine is to verify printing processes with different material manufacturers to ensure ease of prints with different researchers or anyone that's performing the research. This slide shows an example of a partnership that we have with Humobiologics and with our Pyridine and our temperature control device, we were able to achieve great results in terms of precision and accuracy, shown in the images here. So the left image was printed with the osteogelma and this was at a concentration of 10 mg per ml. And then on the far right, the material we were printing with was a humiderm and this concentration was 10 mg per ml. We also utilized, as I mentioned, our temperature control device in the middle picture to achieve even better results in terms of precision.

Speaker 3: 34:41

What's next? So at Periodine, we're constantly developing new products, evaluating the market needs and looking as to how we can innovate in this space. So in the most recent news, we have developed a pressure sensor. It's called the FlowPlus SPT pressure sensor. This was announced last year, so this enables real-time process controls and also lays the foundation for future machine learning capabilities. This is able to monitor pressure as well as temperature.

Speaker 3: 35:12

Our focus remains also on building strong partnerships across the bioprinting field, including researchers, biomaterial suppliers and also machine builders or bioprinting machine builders, and through this strategic collaboration with BioInks and as well as Brinter, we were able to advance the solution to integrate a full system. So you can see, this covers the printing technology as well as the machine, and then, with BioInks materials, we were focused there on the actual BioInks. Together we were able to achieve a plug and play by our printing system, designed to essentially reduce material waste, enhance reproducibility and also accelerate translational research. If you're looking for more information on this, I did put a link as well in the presentation that Jenny will share afterwards, and thank you all. That concludes my presentation, so you can feel free to scan my QR code, connect with me directly on LinkedIn, also contact me via email or through cell phone, text or call, and you can also find our technical information, case studies, white papers our upcoming presentations on our paradigmcom website as well.

Speaker 1: 37:00

Awesome. Thank you, elias. Feel free to put the link in the chat box and I can also upload into the lobby area so that people can see these. I have a couple of questions actually more and more questions from the audience. One is from Bill Harley. Nice talk, annalise. What are some of your software solutions and tools that can aid in optimal print process control over such a large range of material type?

Speaker 3: 37:28

So the way that we're able to utilize the broad range of viscosities and materials is due to our progressive cavity pump design. Progressive cavity pump design so I can follow up with you after. But essentially we're able to have that progressive cavity with the rotor and the stator design that allows the volume principle, volumetric dispense. Therefore we're not pushing pressure or utilizing pressure, we're utilizing more of a mechanical dispense.

Speaker 1: 37:57

Cool. Next question is from Michelle Hernandez. Can patients' own cells be converted to autograph-corrected stem cells to be incorporated into these 3D implants? I think that's the goal, but I don't think we have done it yet. Is that correct?

Speaker 3: 38:18

Yes, and our focus here is to develop the systems where the researchers can use to do those types of work. We specifically we do not handle cells in our facility with our prints. We rely on the partnerships or the universities for that.

Speaker 1: 38:34

Yeah, I think certainly non-human cells have been used for a variety of purposes, research mostly, and I think that's the eventual goal. But I think we're definitely a good five to 10 years from that actually using patients' own cells, but it's not impossible for sure. All right, next question from Payam Ruzard what kind of cellulose you use to print with alginase, nanocellulose or just normal cellulose? You use to print with alginase, nanocellulose or just normal cellulose? If you use nanocellulose, is it nanocrystal or nanofiber? Wow, okay, nanoexpert here.

Speaker 3: 39:12

I can follow up with you. I'm not specifically sure which one that was printed with, but I can definitely follow up with the researchers and get you the answer.

Speaker 1: 39:22

Awesome. Yeah, annalise, if you can, you can put your contact info in the you know chat box address to everyone and whatever link that you think is helpful also to the live audience here. Thank you so much for a wonderful presentation and also for sponsoring this event. So thank you very much. I will see you later at the end of the discussion time. And now I'm going to introduce our next speaker, dr Jorge Madrid-Wolf, with his name, we know exactly where he came from, but that's not true. He is actually educated in Switzerland, now works for Readily3D. He's a scientist for the company, and this is a fantastic company. It really has a very innovative way of creating scalability in the bioprinting space. So, jorge, I'll let you take it away.

Speaker 5: 40:16

Thank you so much, jenny. Thank you very much for the invitation and to all the attendees for being here. It's really an honor for us to participate in this webinar. We're very happy to be able to share our technology with you and, most importantly, today I will not be showing not only what we do, but mostly what our clients are doing with our technology, hopefully to inspire you a little bit on what can be done. So we are a company that makes 3D printers, so we make light-based 3D printers and we do believe mostly that shape brings function. So this is a major question in tissue engineering whether we what like, to what extent shape is necessary for function, and we are true believers that there is an advantage of having the right shape to be able to give the right cues for the cells, for the tissues that we're fabricating, and that there is an advantage to that. So today I hope I will convey a message that there is a need for shape in tissue engineering. So to tell you a little bit more about what we do, we are a spin-off from EPFL. It's one of the two Swiss Federal Institutes of Technology. We're located in Lausanne in this beautiful landscape, so I cannot complain.

Speaker 5: 41:49

It's been a couple of years five years now that we were founded and we commercialize 3D printers with a focus on biofabrication. Our printers are not layer by layer fabrication. How they work is that we use light to project these volumetric doses of energy into our printing volume and truly build the object all at once. So it's a very fast process. It takes typically less than 30 seconds and then there is no need for support like support struts. We are truly printing into these liquid resins and then that can then be washed out and rinsed and then you have your piece able, like you're able, to use the printed part. It allows you to fabricate centimeter scales with a lot of free freedom to make creative geometries, including cavities and contours, and, being a contactless technology, there is no contamination. You get to print enclosed, sterile vials and there is no shear stress, so extremely cell friendly, which also allows you to fabricate very soft materials, also very relevant for tissue engineering.

Speaker 5: 43:03

Here's a little video of how it works. So this is a video from like recorded within the printer. So there's a camera in the printer and this is real time. I did cut off the first 20 seconds of this video because you just have the vial rotating. What you don't see here is the light that is projecting these tomographic patterns. But what you do see is that the object in this case the model of a rat artery not too scale, it's a little bit bigger is being printed truly all at once, and this allows you to have empty channels inside fundamental to recapitulate vasculature ducts, all these very relevant anatomical features, and then you just wash out your construct and then you can reclaim the material that was not cross-linked. So it's a beautiful technology inspired by computer and medical tomography. So how does it work?

Speaker 5: 43:58

If some among you have been to the hospital and got a CT scan, well, how it works is that you basically get x-ray images of your body from all possible angles and then, with each of these two-dimensional x-ray images that you get, you can reconstruct a three-dimensional object inside. So we do roughly the same thing, but we don't use x-rays, we use light, and instead of capturing pictures of the three-dimensional object, we project pictures into the center, and this is what builds the three-dimensional object. So it's like a CT scanner, but the other way around. So basically, what the CT scan does is that you take your little slice of your boat, for instance, in this case, a very like our famous 3D Benchy boat, if you're familiar from it, from additive manufacturing, and you can calculate the set of x ray projections that gives you the reconstruction. Well, we have a powerful computer doing this for you, and then the printer will take these images and then use light visible light to build that three-dimensional object. And this really happens within this polymerization process or cross-linking process. It really happens within 30 seconds. So then the question of okay, can we use shape to recapitulate function?

Speaker 5: 45:22

And today I will be bringing three examples to you on mammary gland, photosynthetic bacterial materials and aligned cartilage and cardiac cells, which are from our clients. So none of the science behind this is actually or the bioprinting is done by us, it's done by our clients, but they're doing beautiful things. So I'm like we're happy to share and like bring forward what they're doing. If you're curious, here are the references. Don't hesitate to take them, take a look. Most of them are very recent works.

Speaker 5: 45:59

So for first I will be showing this work from ATH Zurich. They used our technology to fabricate these models of the mammary gland. So basically, they made these duct models that they lined with cells. So they printed these very soft duct models that they could then line with cells. So they printed this very soft duct model so that they could then line with cells coming from primary cells yeah, primary cells, from human milk samples donated to them, and then, beautifully enough, they could show that these cells, these epithelial cells, were creating these soft, very thin layers of cells, meaning building an epithelium, which is fundamental for these gland-like structures in the human body.

Speaker 5: 46:50

And then, most remarkably, they demonstrated here I want to focus on these two images in the center. The one uh, well, I think I can do a laser pointer, sorry, there you go. So this image here in that in yellow you see this beta casein, so this is a protein that is found in human milk. So they show that their cell, like the cells in their constructs, in vivo were producing milk proteins. And also here in red, you see the red. This is a dye that attaches to lipids in general, so also you had the fatty composition of milk in vitro. So what they were making were these perfusible, duct-like structures that were making like they were producing mimicking lactation in vitro, which I find quite remarkable. Then there is this work on photosynthetic living materials that I found very inspiring and very creative. It's a very different approach to bioprinting. Basically, what the researchers did here was that, inspired by Joshua trees, they created these very spongy like structures, difficult to manufacture with many other technologies but fundamental, so that you could have the bacteria in it pulling the liquid and also enough air and circulation so that there could also be light to for the bacteria into these constructs. And basically what they showed was that they could develop these materials with cells, like with bacterial cells already inside, that they could grow for up to one year and then, beautifully enough, that they could also make capture carbon, sequester carbon through the production of carbon precipitates, so like the non-spiky structures that you see in this SEM image, but also through the accumulation of biomass. So basically what they're? It's a beautiful work in collaboration with their Department of Architecture, in which they develop new materials that create carbonates from 3D printed structures. So a new approach to maybe eventually fixing our buildings with 3D printed bacterial structures, who knows?

Speaker 5: 49:12

Then there is also this other work, this one here we go back to, mimicking human tissues, and this is a nice feature of our technology is that it can be used to fabricate these very fibrous structures, which are great to guide the growth of cells. So here in the hydrogel in which you're printing, so the resin that you use, which can be laden with cells before printing, so you don't have to populate the scaffold afterwards, you can populate it before printing. Well, what you do is that you create this very aligned fibre structure that then cells will use. Here the hydrogel is shown in red and then the cells are shown in green and you see that over the course of the different days these cells begin to align and to elongate. So using these fibers as a guidance allows them to recapitulate their proper shape. So not just having cells that look like blobs, but having cells that are elongated as they should be in native tissue. And then you see that there is an increase in the aspect ratio over the course of time. And what is really nice about this is that it has been used, for instance, to recapitulate the production of collagen by human chondrocytes in vitro. So if you just place human chondrocytes in a bulk hydrogel that does not contain collagen, you will see that, well, they secrete some collagen, but you see that most cells look just like blobs and then there's a little collagen secretion. Whereas if you use our technology to produce this filamented hydrogel structure, you see that first, cells are more elongated, which is more like biomimetic, and, most remarkably, that they are producing these long fibers of collagen that were not there in the initial hydrogel.

Speaker 5: 50:59

And this one I really, really like it's not only can you use it to fabricate cartilage tissue, but also cardiac tissue. So here, instead of loading it with chondrocytes oops, sorry, my bad they load the hydrogel with cardiomyocytes and the alignment allows to replicate this like the typical structure of muscular tissue, which then allows you to have contractile cardiac constructs in vitro. This is also real time, so you have this beating of these cardiac tissue models. So what is it behind what we do in our company is we want to make 3D printing and, most importantly, bioprinting just like basically a tool for the researchers. So we don't want like they're doing amazing science, but their science mostly occurs in the development of new material, so before printing, or in the biofabrication step, so basically after printing. And what we want is that we want to make this step of actually printing to be as easy as possible. So for this we have designed our Tomolite, our light-based printer, so that you can use it with sterile, autoclavable vials. To make it compact, you don't have to have the printer into the biosafety cabinet, it can be just anywhere else in the lab and then you can have your vials prepared in under sterile conditions. There are no open vats, so not much lower risk of contamination and also like no messy surfaces, and then you can also reclaim the anchored resin. So it's a it's very convenient and it's a nice device like it's easy to share and use, which is what we want to do in our technology.

Speaker 5: 52:48

The library of materials is large and growing. So we it's an open platform by design. But we also in partnership with bio inks, our company, a company in Belgium, we have, like we commercialize gelatin, methacrylate hydrogels and polycaprolactone that can be printed with our machines. But our users have also gotten very creative in ways of printing acrylates, thioline-based hydrogels, silicones, ceramics, even glass, and then it's compatible with any light trigger chemistry. So it's a very versatile platform also to develop new materials.

Speaker 5: 53:31

There is also the advantage that as you're printing fast, well, you get replicates fast, so your statistics are more robust with less time invested. That can be very interesting for in vitro studies. And, most importantly, well, what is it that comes next? So we're getting more and more active on making the machine compatible with other forms of printing and stimulation. So we have added these multi-wavelength add-on to our printer which allows us to project light of up to four different wavelengths into the print volume. So you could think of different chemistries, you could think of light stimulation into the construct. There are many ways in which this can be exploited and you get micron, like in the order of 10 micron resolution for all wavelengths, so optical resolution in our projection system. And then we're also incorporating given that we have a camera into the printer. We're incorporating machine vision so that, for instance, we can produce layered sphere models.

Speaker 5: 54:44

Layered sphere models very useful now for spheroid studies, in which you could have different types of cells, for instance, in each of the layers. Also, you could encapsulate organoids that you put into your hydrogel and then build chips around them. So instead of having a chip in which you have to put your organoid inside, well, here you create this soft hydrogel based chip that you can perfuse afterwards with your organoid entrapped inside, and then you can circulate media through it. And also you could make composite materials. So here in this particular video, you have a very stiff mesh so that you can print soft hydrogels dyed in blue without them collapsing, so that the cells will sense a soft material, whereas the researcher will have a stiff enough construct so that it does not collapse over handling.

Speaker 5: 55:35

And with this I just want to conclude. So what we're doing at uh readily 3D is working on versatile cell-friendly bioprinters so that we can enable researchers to bridge the gap between shape and function in tissue engineering and including models, for instance for the mammary gland, contractile cardiac tissue models, cartilage models or carbon-fixing bacteria, for instance. And with this, please don't hesitate to contact us if you have any questions, at contact at readily3dcom. Do look at us, look up us on the internet and, yeah, or through LinkedIn, and I'm happy to take your questions. Thank you very much.

Speaker 1: 56:18

One question, Jorge If people email that email address, are you going to read that email?

Speaker 5: 56:23

Yes, of course we do. We read every email, that's that's his email.

Speaker 1: 56:27

Yeah, why don't you put that in the chat later? We have a couple of questions from the audience. One question is how do you manage to work with cells that? Are they embedded in hydrogel or are they post-seeded?

Speaker 5: 56:42

So both options are possible. For instance, the mammary gland model, that one was printed in a decelularized extracellular matrix hydrogel which did not contain any cells upon printing but then it was seeded with epithelial cells the example of the bacteria, for instance, or the cartilages or the cardiac tissue those were hydrogels that contained cells prior to printing. So you have this hydrogel with cells mixture that then you build the scaffold in and then you have your cells living in their house. So you don't have to build a house for the cells and then to move in. They are into, like in their house when it gets fabricated basically. So both strategies are possible thank you for clarifying that.

Speaker 1: 57:27

Next question from vj how does the transparency of material effect affect the print fidelity? How do you overcome overexposure?

Speaker 5: 57:37

yes, so optically like. Our technology works best with optically clear materials, so we can also print in hydrogels that contain cells. It's not that they have to be transparent, it's that they have to be translucent. So we cannot print in opaque materials. This is not possible. Light must penetrate through, but some degree of optical transmission is necessary. So most hydrogel based materials are optically quite clear. Extracellular matrices. You can make them clear without needing to introduce things. It's just basically properly mixing them in an aqueous medium.

Speaker 5: 58:23

So yes, you do need some optical transmission to fabricate things in them.

Speaker 1: 58:32

That is a requirement. Is the machine going to tell the person who's using it that if the transparency is adequate, so machine is no, but our guidelines do okay, you have a guideline okay that's good to know exactly, yes, all right. Next question is it possible to work with multi-material, multi-cell approach with this technology?

Speaker 5: 58:52

I think you kind of addressed that yes, so it is possible and it has been demonstrated, to print in heterosellular mixes.

Speaker 5: 59:02

So basically, a hydrogel containing several types of cells inside, or doing it sequentially, so you can do it at once. If you don't need to have your cells placed at different spots, like, let's say, if you want to make a tissue in which you have, I don't know, umroblasts and vascular cells together, well, you can do this by mixing them from the start. But if you want to separate them, you can then actually sequentially include each of them, each of the different materials with different types of cells in different locations, so you get also spatial resolution from this. There's also a beautiful example of using light not just to print but also to decorate the hydrogel with growth factors. So you can engineer your chemistry so that you can attach different molecules at different places into the hydrogel and then you can guide cell differentiation spatially. So this is also like some hydrogels, in particular, thioline. Chemistries are very versatile and open great avenues for this. So don't hesitate to contact me on this. I can give you more information on how to use light to decorate your constructs spatially.

Speaker 1: 1:00:18

Cool. I've seen quite a few articles recently published just within the same jail bath just playing around with different light settings and actually can get different kind of material or mechanical properties coming out.

Speaker 5: 1:00:34

Exactly. That's also a nice feature is that you can use the light dose to control this degree of stiffness, so you can have material that are softer in some regions or more porous in some regions, and then you can use this to guide your cell maturation afterwards. So it also opens lots of possibilities, and then, yeah, researchers get creative with these opportunities.

Speaker 1: 1:00:59

Yeah, fascinating. So, Jorge, yeah, feel free to put your contact or whatever format you want people to get in touch with you and see you soon. Again, I'm going to introduce our final speaker, but not the least is.

Speaker 1: 1:01:11

Dr Carolina Valente, and we truly have a really international speaker here. I mean, we have panels, people move to different countries and start a company, and Carolina is the CEO and co-founder of Voxel Bioinnovation, a startup located in Canada Vancouver, is that correct? Victoria, yeah, and then I really have seen this company from zero to one and she's at a very good stage right now Still early, but very promising. Um, carolina, I'll let you take away.

Speaker 4: 1:01:47

Um, thank you, jenny, can you hear me? Okay? Yeah, perfect, perfect, okay. So hello everyone. I'm dr carolina valente. As jenny said, I'm the ceo and cso of Voxel. My background is in tissue engineering and bioprinting and Voxel was born out of me actually using biopsy samples from the hospital and trying to work with those biopsy samples. Those were breast cancer biopsy samples and they were hard to obtain. They were hard to manipulate and I thought there has to be a way to do this artificially, and that's how Voxel was born.

Speaker 4: 1:02:21

So the focus with Voxel is creating vascularized tissue models, and we are starting the field with oncology. So this is like the idea of our tissue. This is, of course, much bigger than the reality. But a little bit more about us. Voxel was founded in 2020, so we are five years old. We are operational in Victoria, bc, canada, so very close to Vancouver. What is important about Voxel is we have built our entire technology, which means that everything that we use has been developed and created by our team. We hold 100% of our IP. We have a 12,000 square feet space facility in which we are producing the tissues, synthesizing the bio-inks, creating all the assays and running all the screening processes for these tissues inside of our facility and as many other types of bioprinting technology. What we see is there are different approaches where we can go. We could go to the personalized medicine space, we could go to the tissue replacement space or organ replacement space.

Speaker 4: 1:03:31

Where voxel is playing, at least in the initial space for now is in the drug development process. So while we see the drug development process. So while we see the drug development process for those of you that don't know, it's the process in which pharmaceutical companies go to take a drug from an idea all the way to the market. While we see. This is a long process. It takes about 15 years, so one, five, 15 years and costs more than $2 billion. And the problem with this process is, once you're testing the drugs in the lab, you're having some indication if that drug is working or not working and then from there you're making decisions in when this drug is going to be tested in humans.

Speaker 4: 1:04:12

The challenge of what is happening is when the drugs go to phase one, clinical trial, which is the first time that those drugs are tested in humans. Most of them fail the failure rate. When we think about oncology field, which is again the first field box I was playing a role in is about 95%. So there is a lack of translation, clearly, a lack of translation from the lab to clinical trials. We need more complex technologies. So these animal models have been used as a gold standard for a long time. That is not much translation.

Speaker 4: 1:04:47

With animal model. We have been curing cancer in mice for many, many years. So the idea is, can we create a platform that can actually provide reliable and translatable information? And that is this movement, that is this change, and that is in this change that Voxel is also incorporating some of the approaches that we are taking with our technologies. What we are seeing is a change in the market, a change in the ways that drugs are being tested and the way the tests are being done right now. So the FDA Modernization Act came in 2022 to propose alternatives to different types of animal testing and to be using this type of technology is called NAMS, which is New Approach Methodologies, and some of the alternatives to test, to do the animal testing, was provided as bioprinted tissue models On top of computer models, which, again, we are seeing a lot of AI type of companies that are also playing a role, and they are very complementary to Voxel's technology. Fast forward from 2022 to now. What we are seeing. 2025 has been a big year with many, many proposed new changes, with FDA proposing a roadmap to reduce animal model usage in preclinical testing, starting with monoclonal antibodies and then moving to other drugs later on, and we're also seeing a shift in funding and the way that experiments that are only animal model, without using any other technology or complementary technology. The funding is changing, the landscape is also changing, so Voxel is here as a solution. What we are really focused on in Voxel is using bioprinting technology to create vascularized tissue models, starting now with the oncology field.

Speaker 4: 1:06:38

The beauty of our technology is the vasculature is fairly complex. Our tissue is scalable. It's very reproducible. We have a very, very high-resolution bioprinting technique and, as Jenny was saying, it's very beautiful to sit in this panel because each one of us is using a different type of bioprinting technique printing technique and the beauty of this tissue. They are created with a thoughtful approach towards the biolink and the materials that we are incorporating in there and, of course, they are free from any physical boundary. So we incorporate three pieces. So I call these three pieces of the puzzle one, two and three that come together to create number four, which is our tissue models. So one is our software that develops the 3D vasculature environment stands to our printer and the printer number three in there, very, very high resolution. We go deeper into it and the materials are also very important components. So the integration of these three components, they come together to create the tissue models and I'm going to show you a very quick video that shows the creation of this human-like cancer tissue models by incorporating our very, very high-resolution bioprinter together with our software that generates the blood vessels and our materials, that is, our printer's cartridge.

Speaker 4: 1:07:58

The result is a model that contains real cells and an artificial vasculature and the idea is very simple let's inject the drugs through the vasculature and see how the drugs are moving from the vasculature into the rest of the tissue. This is exactly the same way that happens inside of the body and can we get initial insights on how this drug is functioning or not functioning. So I will focus a little bit on on the bio ink and a little bit on the printer before I go to the models. But the ink, as I said, it's developed by us and the goal with this ink is really being able to mimic that extracellular matrix environment and the reason for that is that stiffness, the chemical properties, the behavior of that environment will affect how cells behave and of course our goal is to get as close as possible to the human environment. Our bioprinter is a two-photon polymerization bioprinter. Our resolution is 500 nanometers and, just out of curiosity, the focal point in which that printer, the laser, makes inside of the material, when in the printing process that focal point is called the voxel that's where kind of our name came from.

Speaker 4: 1:09:17

We spend a lot of time making sure that the tissues coming out of this printer contain at least 80% plus cell viability. These tissues, they are created to be able to be viable and used for 21 days and we are extending that to a month. They have a customizable vasculature, they've recreated the tumor microenvironment and the goal here is to be able to run efficacy and vascular toxicity in the same platform. What you see there in green in this sparkling image is a simulation of the experimental results of mimicking a chemotherapy drug in green and the biologics larger particles in this sparkling image. So with this platform we can really create this. We have this multiplexing capability, so in the same platform you can run multiple tasks and you can really manipulate these tissues as if it was a real tissue. The tissues are printed inside of a chamber that you can use to mimic the flow, and we do have a high-throughput capability, with these tissues also being done in a well-played format. So we are not asking researchers, pharma we're not asking them to do anything differently. We are asking them to do better and to use voxel's tissue instead. What you also see there in the last image on the bottom right is our beautiful heel vac. That is our endothelial lining on the vasculature.

Speaker 4: 1:10:43

So in my next minutes here that I have, I'm going to focus on very different case scenarios that we use to study this technology and I'm not going to go too deep on anything, but I'm going to give you a bit overview of what we have been investigating. Our first study was a triple negative breast cancer tissue that is a part of my mom is the inspiration towards this is what we started Voxel. My mom had triple negative breast cancer throughout her entire life, so we started in there and we investigated this with this tissue, with Paclitaxel, which is a very commonly used chemotherapy drug, and what we saw is, of course, severely increased resistance but on top of that, non-molar concentration of sensitivity, which is really, really important. And lastly, what we also observed is a specific phenotype behavior of those cells in that environment. So with this data we decided to then move forward towards the lung cancer environment, and the lung cancer environment is a project with two partners in Germany. These are patient-derived samples.

Speaker 4: 1:11:53

What we created is a tissue that is no small cell lung cancer, which is about 80% of the lung cancer type. So it's a very, very serious cancer type and what you see there in pink is the formation of these very beautiful spheroids of the cancer, the lung spheroid and after that we injected T-cells. So this group is working with us on they are developing TCRT, so basically T-cell receptor therapy type, and we are injecting those two cells to the vasculature and seeing T-cell extravasation, labeled in green in there, from the vasculature into the cancer area. What we are really going forward now is increasing the complexity, as I mentioned, is not just thinking about the noctilio cells, the cancer cells, the stroma cells, which play a role in that environment, but also incorporating the immune system, which is highly, highly relevant, especially in this immuno-oncology space, which is the space that we have been doing some experiments right now. Combining with that, we also have a very strong hardware and software team that works parallel to our tissue engineering team in really making sure that all the flow that is happening inside of the vasculature is actually physiologically relevant, because this is fairly important the delivery of the drugs. This will play a huge role on how these drugs are distributed and it will affect the tissue. So we do computational fluid dynamics and the goal really is to make sure that we are matching wall shear stress, so how much stress the cells are feeling in there, what's the flow that is passing to the vasculature and getting to a point where we are operating under a range of human capillary vessels. So again experiments, then a mimicking simulation, simulations then tele-experiments. So that's the go back and forth. But the idea here is really mimicking what the cells are experiencing in that environment, because we also develop our own bio-inks. We also have been testing our own bio-inks with extrusion printers. The ink is universal in a sense, that can be used in any bioprinting type. It's also the ink that we use for our tissues. So we have done multiple studies with our inks, with non-small cell lung cancer, but also triple negative. The ink behaves beautifully in the extrusion, which also display a very, very high cell viability. So good shear-fitting behavior, which is what you need, and also temperature-dependent, which means that you can tune the properties of that ink. Lastly but not least, we also have a collaboration with the BC Cancer. So the BC Cancer is a cancer institute here in BC that is connected in our case here our tissues and then correlate that with clinical data and animal data that they currently have.

Speaker 4: 1:15:07

Today. You only heard from me, but it takes a village to get to where we are and, as Jenny mentioned in the beginning, we are fairly early stage. But Voxel has done so so much in this past five years and we are about to accomplish a lot more in the upcoming months. There is a lot of news that are coming from Voxel that are very, very exciting, but it takes a village to get to where we are. So we have a very strong management team here Graham that is leading the business development, dr Boyce that is leading the inks, dr Poon that is brilliantly leading the tissue engineering development she's absolutely brilliant and Jeff Doyle that is leading the engineering side hardware and software. Our board has also been very, very strong. So we have Marie Helene, which is the president of Alta Sciences, which is one of Canada's largest CROs, and we also have Doug Yeight that used to be the CFO of Novo Nordics Canada for the past 15 years.

Speaker 4: 1:16:06

Our mission is really to accelerate the drug development process and allow therapies to hit the market sooner. I'm very proud to be leading this company and to say that VoxR is 50% women and 50% immigrant, and together we shape the future of preclinical development. And before I close, I just want to say andy garcia is there, because we are going to have a short documentary with him being released next month. So the moment is really the journey I'll also share with you. Um, thank you very much. I'm happy to answer any questions fantastic, love it.

Speaker 1: 1:16:43

Maybe one day we can produce our own documentary about this whole. Thank you very much. I'm happy to answer any questions. Fantastic.

Speaker 3: 1:16:47

Love it.

Speaker 1: 1:16:48

Maybe one day we can produce our own documentary about this whole community. It's such a fascinating group of people. All right, we've got a couple of questions from the audience. Ok, let's see Bill Harley. Fantastic talk, Carolina. What are some of the key features you're focusing on to overcome reproducibility obstacles in your oncology models?

Speaker 4: 1:17:07

Yeah, the reproducibility is important. So reproducibility, we speak in different ways. One of them is from the tissue structure itself, so that's very, very reproducible. As I said, bill, our technology is 500 nanometer resolution, so the tissues, they look and behave exactly the same way. But then there is a reproducibility on the cell type too. So we operate on the very strict parameters of coefficient of variation within the company. So we're very, very serious QC. So all tissues are tested and all tissues are validated to be within 10% of variants in there. So when people are working with us, the tissues they look and behave the same way, and that is very, very important, one of the challenges when we think, for example, about organoids and other types of preclinicals. So you're absolutely right there on the point in which reproducibility is highly important. Thank you for your question.

Speaker 1: 1:18:02

Yeah, that's a great question. Also, that's the strength of bioprinting itself, so we have improved precision in everything, okay. Another question from Michelle Hernandez Are patients' own biopsies placed in these vascularized in vitro for determination or best cancer therapy?

Speaker 4: 1:18:21

That is the future, michelle. So this is the whole reason why I started this company was to go towards that in the future. We call this a space where it is a personalized medicine space. So it's not necessarily a biopsy sample, but it would be, for example, maybe extracting a biopsy sample but taking the cells and then replicating that inside of this tissue, so the cells of the patients that are mixed with our bio-inks and recreated this tissue. So this is definitely the future where we see Voxel's technology potentially going, and that is a very impactful field. Right, it's a field in which you're dealing directly with the patient. Regulatory process is different in there versus the preclinical right now that we are playing a role. So that's also something to consider. But it's definitely something that I have in mind and that was the reason why I started this company. So, thank you. I hope that answered your question. So, thank you.

Speaker 1: 1:19:14

Yeah, I mean I think your product has impact in multiple fronts. One is we have a rise of cancer, especially actually in the younger population, for whatever reason, and two is the complication and mortality coming from the treatments itself is actually a significant percentage of mortality from cancer. So I don't know if people knew that everything therapeutics that didn't really work out, you know, actually harm you as well. So it really is a battle on two fronts. Let's see another question how long does it take to fabricate the vasculatures shown using the two-photon printer that you've shown here?

Speaker 4: 1:19:52

Yeah, so fairly fast. So we can print that in minutes. So at this scale it's minutes in here, so these tissues can be fabricated fairly fast. Right now at the company we have parallel bioprinters, so we have two. Right now the printer is in ours, it was created by us and we have a couple more in development in the pipeline. But we are talking about minutes scale here.

Speaker 1: 1:20:15

Awesome. Well, thank you, carolina. I'd like to invite all the panelists to be on screen now we're reaching the final stage of our conversation here, and thank you so much for the great presentation, carolina. Always a pleasure to have you, thank you. So I have posted a couple of questions that I have, but I want to start with a recent workshop with FDA and NIH, because you know, we have a new administration, new leadership, and I just want to. We have a new administration, new leadership, and I just want to know, from a regulatory perspective, do you guys have any comments of you know what they can do better to enable this field in general?

Speaker 4: 1:20:53

I think I think, like I think they are starting we have been seeing. It was interesting because the FDA Modernization Act in my point of view it came out in 2022 and from there on it kind of stayed more or less the same. No one was talking too much about it and we saw the European division is a lot more active on that, but no one was really talking too much about it in the FDA side. And then this year we have been seeing big, big changes, or at least big proposed changes.

Speaker 4: 1:21:21

Um, since q1 until now, like they announced the phasing out in april. They announced the nih change. The nih is announcing changes right now in june. So things are definitely evolving in the right direction. Um, and they have created what is called the I standand program. That stands for Innovative Science, technology Approaches of New Drugs, and this program is really for companies like Voxel, like us talking here, that can engage with the FDA in a way to show case that the technology has the potential to really play a big role on the platelet count side. So that's my take.

Speaker 1: 1:21:59

Fantastic Carolina. If you don't mind, can you type that into the chat so that people can search for it. Absolutely, absolutely. And, mike, what do you think, on the therapeutic side of in terms of regulatory pathway, is easier for you or harder for you? Now, yeah, you know, I think they do better.

Speaker 2: 1:22:14

I think by and large we're in kind of a wait and see mode right now. There's been a lot of talk about things that could improve and you know that would be wonderful and welcome. There's also, you know, some real challenges right now. You know, for folks who are looking to schedule an interact meeting. Right now those are basically frozen. You can't really get one and you know that's definitely going to be a governor for some kinds of programs out there. You know I think they're looking at two years out right now as the next date you can schedule some of these meetings and I think that's largely due to staffing. So we'll see how that course corrects. But I do think that you know early interaction with the agency is a key to successful therapeutic development and right now, you know it would be really encouraging to see more emphasis put on that as we move forward.

Speaker 1: 1:23:05

Yeah, let's hire them back. That's what I'm going to say A lot of firing and a lot of rehiring. Anyways, next question is you know we often talk about, you know how all the products we're talking about on this webinar are going to reach human beings next 10, 20 years? That's just way too long. I want you guys to tell me what I'm supposed to be, what I could see in the next three to five years. I'll start with Mike, since you're on camera now.

Speaker 2: 1:23:34

Yeah, I mean we'll be in the clinic in less than three years, We'll be in human patients and we expect, you know, approval. This decade is a possibility for what we're working on. We also have a pipeline of other therapeutics that we expect to be able to expand pretty dramatically beyond just insulin delivery. As we, you know, today platform companies are not really in vogue to finance, but this, fundamentally, is a real platform technology.

Speaker 2: 1:23:57

So we have a pathway that can let us, you know, address some other really significant challenges in the world where, over the course of the next decade, we could introduce two to three therapies into not just the clinic but into actual routine patient use. And you know, it's going to take significant investment to get there, but it is something that we're, you know, we believe is entirely possible.

Speaker 1: 1:24:17

Not just investment, but hard work and persistence and, you know, really put your heart into your life, into it. And you know, I can see this. Your company can be or every company here can be the next nova nordisk, for example. It's the company I have in mind and, uh, yeah, that's awesome. Uh, okay, what do you think next three to five years, what can you see?

Speaker 5: 1:24:37

so I think that that there is one way in which we're already seeing this, and it's not only in the clinic, but also as consumers, for instance, for cosmetics and these kind of products, where we see that tissue engineering is becoming more and more relevant, and I think that more countries are, for instance, moving faster and faster towards the replacement of animals into these studies and then going for 3D culture, which is a great opportunity in the sense that, well, there are reasons to be cautious, right, but here there are many reasons to go fast and be aggressive, right, like, reducing the use of animals is important, but providing safe cosmetic products is extremely important too. So I think this is something that is happening, not in three years, but actually now, and it's a very exciting field actually.

Speaker 1: 1:25:33

Yeah, I mean, aside from the ethical issues with animal mottos, is that they also don't work very well because they're very different from human beings.

Speaker 5: 1:25:43

So yeah, Carolina Engineering, and then the complexity of the tissue models that we're able to, as a field, produce, is already being able to recapitulate those things.

Speaker 1: 1:25:57

Yeah, exactly Carolina. What do you think? Three to five years.

Speaker 4: 1:26:08

I think we are going to start seeing we won't see a full replacement of animal models. That is something that is important to emphasize in here. Right, they have a certain role on organ integration which is very, very important and difficult to explore right now individually without being, again, an integrated system. But what I think we'll see in the drug development itself is this NAMS type of technology really being one of the key tools to get to clinical decisions. So I think it's going to be a little bit in the beginning complimentary, which is it's normal. It's a new technology. People are worried. The safety is a big deal here, as it should be. The beginning complimentary, which is it's normal, it's a new technology. If people are, world safety is a big deal here, as it should be. So I think in the beginning it's going to be a little bit complimentary, as it is right now, until a point where it starts being replacement and then we want to get to replacement. So that's where I believe the field is going in the in the three to five years range and longies.

Speaker 1: 1:26:59

What do you think? It's three to five.

Speaker 3: 1:27:08

Yes, on our side of things and my company so we have technologies that are utilized already in FDA processes, where they're approved in terms of pharmaceuticals and things like that. But on the bioprinting side of things, we're expecting the future to push towards the FDA approvals on everything. So we're working to make sure that our systems are able to be compatible and approved within that spec.

Speaker 1: 1:27:34

Great. Okay, we have a question from the audience for the panelists. Great to see a range of bioprinting processes here. I would love to hear a debate of form versus function. I think somebody I think, jorge, you mentioned it right A form is more important. But anyone who disagree with that statement is the question and love to hear some verbal fistfight on this.

Speaker 4: 1:28:02

I think it's form leads to function too, so I think it's more like that. It's not what is more important. I think they are very, very parallel, and that's the reason why the body is fully 3D right, because form leads to function, and I think that's more like Georgia. I don't want to speak for you, but I think it's also a little bit of the intention here, so I'll pass it to you.

Speaker 5: 1:28:26

Exactly it's how can we enhance function from form and from shape? Right, it's beautiful, right, that our cells are able, for instance, to gauge, for instance, curvature and, based on that, secrete more or less of a given protein. And these kind of like, very like micro scale physical cues are necessary to recapitulate our anatomy. So there is definitely need for shape so that we can recover function. Function at the end is our very goal. Right, it can be nice to have a beautifully shaped 3D printed construct, but it's actually what happens later on in the biology. That happens later on. That is relevant for clinical or therapeutics studies that come afterwards, but shape is necessary to mimic those.

Speaker 2: 1:29:26

Yeah, I would add there's no question that you know there's a complex structure-function relationship as a hallmark of biology. We understand that and that you know. For most complex biological processes there's physical cues, there are interactive effects, there's signaling that's happening between the cells and their microenvironment around them, and those are you know all. There's an enormous complexity to that, and so being able to recapitulate that becomes really important. We like to think about the cell as the thing that does the work, but cells never live in isolation, right? There's no cell in your body that's not contacting with and communicating with a ton of stuff around it all the time. So you have to give it the right environment, the right extracellular matrix, the right communication process, and what I would argue is we often forget that the body is continuously remodeling, and so you have to acknowledge what's the environment in which I'm working and how is that remodeling going to also affect it?

Speaker 2: 1:30:24

I think about this a lot when we think about blood vessels. Years ago, it was very much in vogue to think that if we were ever going to 3D print a tissue, an organ, we're going to need to be able to print all the way down to the very last capillary in that structure before we ever thought about implanting it and, frankly, that's insane. Right, we're never going to have to do that, because no tissue in your body has a static capillary network. They're constantly being trimmed and regrowing and this is a constant evolving process. So we have to think of anything that we're manufacturing to go into the body to accommodate that same kind of environment, and so thinking about the dynamic environment and what can you give the body where it is the right structure and function to start. But it's also giving the body the cues hey, remodel over here to make it perfect. That's also a really important part of what we're doing.

Speaker 1: 1:31:17

Yeah, that's really well said. Annalise any comment on that?

Speaker 3: 1:31:22

I don't have anything to add, but I also agree with all the other panelists.

Speaker 1: 1:31:27

Yeah, I think bioengineering really is a truly perfect embodiment of the combination of engineering mindset and also the understanding of the complex biology of human beings. And in fact, I would say 90% of the body of knowledge is probably not available yet and we're still discovering it every day. Well, I may add to that yes, please.

Speaker 5: 1:31:49

I don't think that we would need to figure everything out before we don't. Yes, exactly Like if we give enough like, as you said, Mike, an environment that is supportive enough, then we should also let biology happen, right, and this should be the actual quest.

Speaker 1: 1:32:10

Great. So I have one last question. I think a lot of people here already addressed that question, which is scalability of the technology. I think five, ten years ago I wouldn't be able to even ask this question, but now I would like to ask you know, what are the scalability strategies you have? You know we hear a lot of things in terms of machine learning, automation, data-based innovation. I'd love to just to hear your thought on what is your strategy moving forward from here.

Speaker 4: 1:32:42

Well, on Voxel's end, definitely automation. So there's a lot of automation that is going into the printers right now. The tissues are, of course, they are small, so being able to print them in a large quantity or moralize at the same time to guarantee, again, no batch-to-batch variation, is also something that is very, very important. So, yeah, integrating AI in our printing process, we're integrating automation after the printer has read and it starts printing to really streamline. So high-throughput is something that we are keeping in mind and something that is also important on this field.

Speaker 1: 1:33:18

And what is the number that you're aiming Carolina at the moment? The throughput.

Speaker 4: 1:33:25

So right now we are putting our plates at 24. And so it simulates a 24 well plate, and of course we want to increase and go even more. 96 is the Holy Grail, but it's also we need to think about. It's not just high throughput, it's ease of usage and everything else that comes with it, right? So having more tissues doesn't necessarily mean you're going to have more data if you don't know how to manipulate them in a correct way. So I would say we are starting with 24 and seeing the idea with Voxel's platform, because it should be used right before animal models. We are not talking about thousands of candidates at that point, we are talking about tens of candidates. So, to put it important, but so it is. As it was mentioned, reproducibility and guaranteeing that the data is um is at least in agreement with each other got it slow but steady mike, not, not, not too slow, not too slow, not too slow.

Speaker 4: 1:34:23

We started this, it was taking eight hours to print one tissue, so we have come a long way from eight hours to a few minutes.

Speaker 1: 1:34:28

That's exponential. Yes, I agree.

Speaker 2: 1:34:33

You know, from our perspective I tell people all the time the beauty of working in a 3D bioprinted environment is that 3D printing, at its core, is inherently automated from the very first time. You do it. Right, you're talking about a robotic three-axis gantry movement G-code. We're talking about things that are inherently easily thought of in terms of the scale-up model and mentality. You know I'd be really interested in some of you know Annalise's experience with sort of some of the small to large scale up, because we're talking about things that we have analogies from lots of fluid deposition applications and things that folks like Viscotech are really, really good at. From our perspective, when we think about a therapeutic, you know there's 8 million people with type 1 diabetes in the world, so you know we would like to be able to service as much of that population as possible as quickly as possible, and the good news is that's a tractable problem, right? We're talking about on the order of thousands of constructs a day, not on the order of millions of constructs a day, and thousands of constructs a day is actually really easy to figure out.

Speaker 2: 1:35:32

One of the things I didn't get to talk about earlier with our technology is it's much, much faster than most of the deposition-oriented 3D bioprinting technologies.

Speaker 2: 1:35:41

So we've done, I think, some of the fastest material deposition work in the world because we're able to work inside of that bath and we actually gain certain benefits from working at higher speeds. So some of the work that we do inherently means that getting to that kind of scale of thousands of constructs in a day is really easy to see the path forward on, to that kind of scale of thousands of constructs in a day is really easy to see the path forward on. And so you know, combining that sort of inherent automation that exists to begin with, plus you know the speed increases that we're able to take advantage of. And then, finally, you know we have IP around and are really excited around some of what we've done with in-process imaging, because what we print is immobilized like some of the kind of resin thought process. But now we're doing deposition. We can actually image and identify exactly what was printed in real time while we're printing it, which is really impossible with any other sort of deposition oriented approach.

Speaker 1: 1:36:33

Yeah, totally that's exciting, okay, Jorge.

Speaker 5: 1:36:40

Yes, so currently, when you see these studies, n equals 3, 5, if you're lucky and you definitely need to go beyond that, yeah, I think and I will second Carolina's comment on this that you need like we want. When you have like, in biology, you will always have big standard deviations, but you want that standard deviation to come from the biology that you're studying. So if you have cells from different donors, of course there will be variability, but you don't want the variability to come from the manufacturing process itself, and that is the challenge and that is what we're working on on making the technology precise and reproducible enough so that the variability in the data actually tells you the story about your biology and not about the manufacturing process Exactly.

Speaker 5: 1:37:36

So this is what we invest our Swiss engineering in, on making things more and more precise.

Speaker 1: 1:37:45

Like the watch, Like the watch exactly.

Speaker 5: 1:37:48

Yes.

Speaker 1: 1:37:49

Annalise any final thought on this.

Speaker 3: 1:37:52

Yes, with Fisco Tech, and in terms of scalability, as I mentioned, we currently have systems in full production stages. It's not in a bioprinting process, but in aerospace and automotive. So we currently have systems in full production stages. It's not in a bioprinting process, but in aerospace and automotive, and pharmaceuticals. So that's where our expertise lies. So it's common for me to be over projects where it's more of a lab scale design at first, and then it goes through clinical phases and then into full production. While that's mainly around pharma I mentioned, it's not as much on the bioprinting side, but we hope that that's where it's trending. And, with that being said, so our focus on the bioprinting side is to have that full process control over speed, over pressure, over temperature and things like that that we've developed our devices to. And then another interesting one is having a system where you can essentially have multiple paradigms next to each other on the same access, printing different materials at the same time or together.

Speaker 1: 1:38:57

So that's the last thing I wanted to add. Yeah, that's awesome. I think this panel is really embodiment of where the frontier of Bible printing is, and I'm really excited to be able to witness the evolution over the years. And again, I want to thank all the audience and the speakers to be here together and have this conversation. I think I learned a lot personally. I hope you did too, and this recording will be on demand free on Zoom, so if you have any colleagues or friends who can benefit from this, feel free to share the link. It'll be here for about two weeks, so keep that in mind. And well, thank you everyone for coming joining us today and I'll see you next time next month, in fact, 3d printed pharmaceuticals is what we're gonna do. Okay, see you later next time. Thanks, thank you.