The Lattice (Official 3DHEALS Podcast)
Welcome to the Lattice podcast, the official podcast for 3DHEALS. This is where you will find fun but in-depth conversations (by founder Jenny Chen) with technological game-changers, creative minds, entrepreneurs, rule-breakers, and more. The conversations focus on using 3D technologies, like 3D printing and bioprinting, AR/VR, and in silico simulation, to reinvent healthcare and life sciences. This podcast will include AMA (Ask Me Anything) sessions, interviews, select past virtual event recordings, and other direct engagements with our Tribe.
While there is no rule for our podcast content, the only rule we follow is to provide our listeners with a maximized return on their attention and time investment.
Follow us on Facebook, Twitter, and Instagram @3dheals, and check out the links in the show notes.
3DHEALS Links: https://linktr.ee/3dheals
🛑 Disclaimer
The content of this podcast is for informational and educational purposes only and does not constitute medical, legal, or financial advice. The views and opinions expressed by the host and guests are their own and do not necessarily reflect those of their employers, affiliates, or any associated organizations.
While we discuss emerging technologies in healthcare and 3D printing, listeners should consult qualified professionals before making decisions based on the information shared. The mention of specific companies, products, or technologies does not imply endorsement.
This podcast may reference early-stage innovations and concepts that are not yet FDA-approved or commercially available. Always follow regulatory guidelines and ethical standards when applying new technologies in clinical or professional settings.
Would you like this disclaimer read aloud at the beginning of each episode, or placed in the show notes?
The Lattice (Official 3DHEALS Podcast)
Episode #94 | Advances in Biomaterials for Medical 3D Printing (Virtual Event Recording)
What truly makes bioprinting possible isn’t just 3D printers. It's important to understand the materials that flow through them. In this virtual event, we explored the world of biomaterials for tissue engineering and how chemists are shaping the future of regenerative medicine through careful material design.
On demand course: https://3dheals.com/courses/advanced-biomaterials-for-3d-printed-medtech-and-biotech/
YouTube highlights: Here
Our editorial event recap: https://3dheals.com/what-are-the-latest-advances-in-biomaterials-for-3d-bioprinting/
Bowman Bagley, Vice President of Commercial at CollPlant, introduces recombinant human collagen made from genetically modified tobacco plants. This approach avoids animal-derived components while improving performance. The collagen can be concentrated to higher levels and modified more effectively than traditional sources, producing structures that support tissue regeneration while staying printable.
Dr. Janaina Dernowsek, Co-Founder and CEO, takes us inside the Quantis Biotechnology platform, where her team has developed a way to create human extracellular matrix (ECM) from bioprinted tissue constructs. By using dermal-like tissues as bioreactors, they harvest complex protein networks that promote cell growth without triggering inflammation, opening new possibilities for skin regeneration and beyond.
Dr. Riccardo Levato, highlights volumetric bioprinting, a method that uses patterned light to form entire structures within seconds. His team combines material chemistry with advanced design techniques, allowing printers to respond to cellular environments in real time and build vascular networks that support tissue function.
Dr. Jasper Van Hoorick, Co-Founder and CEO of BIO INX, addresses the need for standardization and confronts "biofabrication deception". He describes how his company creates consistent, high-performing materials tailored to specific printing technologies. This work helps make bioprinting more reliable and accessible for researchers worldwide.
Finally, Dr. Scott Taylor, CTO at Poly-Med, discusses absorbable synthetic polymers that provide mechanical support during tissue regeneration and then safely degrade once their job is done.
Whethe
Subscribe to our premium version and support the show.
Follow us:
Twitter
Instagram
Linkedin
3DHEALS Website
Facebook
Facebook Group
Youtube channel
About Pitch3D
All right, looks like the webinar started for us Without me and this just automatically started Good morning. I'm glad we're on time, so you're never late for Zoom meetings and we I have founded 3D Heels about almost 10 years ago and with three mission. The number one mission is to educate the public about the application of 3D printing and bioprinting and related 3D technologies in healthcare. I think people's understanding of the technologies and its real use is was shallow and I know that understanding about 3D printing and its power is now more deepened and I hope our educational seminars like this can really deepen people's understanding and be excited about it and co-develop new technologies. Number one is education. Number two is we want to have a networking experience because I want people from different disciplines to talk to one another and not just to be isolated people from academia, entrepreneurship, startups, industries to really sit down, talk to one another in a very informal way but fun way, and educational and maybe even co-start projects and companies together. Number three mission for us is a program called Pitch3D. We help early-stage startups with fundraising and this is a free program that we offer for early-stage startup, which means before Series B, so if you're from pre-seed all the way until Series A. We can help you. We have a process that can connect you with institutional investors and there's no cost.
Speaker 1:Even though material science it didn't seem should be a very wild topic, like 3D printing, organ and stuff but I think the fact that the event is very popular is people understand how important material science is, its role in biofabrication, in 3D printing for medical devices, and its complexity. And the other thing is this space is definitely growing rapidly and I have a phrase asking do you chemists, rule the world? Just like similar to do software, eat the world. I think chemists do actually very much in control of this world that we're in for biofabrication. So, without further ado, I'd like to introduce the first speaker, bowman Bagley, who is a very well-known serial entrepreneur. He was the CEO for Advanced Biometrics, which was recently acquired by BICO, but now his new role is focusing on leading commercialization for Copeland. Bowman, I'll let you take it away.
Speaker 2:Thank you, I'll share my screen.
Speaker 1:Yes, please.
Speaker 2:Does that look good?
Speaker 1:Yes, perfect.
Speaker 2:Great Thank you, and thank you for this opportunity to speak, and I am not surprised that this event is very popular, because, with tissue engineering and bioprinting, a lot of the results that we see are so tangible and visual. You can see a scaffold that someone printed, or a skin model or a tissue, and so it's very exciting. You can see the progress and the improvements very viscerally every single day, and so I'm very thrilled to continue to be working in this space every single day, and so I'm very thrilled to continue to be working in this space, and I'm here with let me see, did I even? There we go? I'm here representing Cold Plant and specifically talking about the recombinant human collagen for biofabrication. So Jenny gave a great introduction. I don't have much to add to that. At Advanced Biomatrix, I spent 10 years introducing new biomaterials for 3D bioprinting, tissue engineering, cell culture research. I worked at a genomics company and I've done some angel investing, and my background is in neuroscience and business, and so currently I'm the VP of commercial North America for Coal Plant and I'm just really excited to be working with this fun material and looking forward to sharing some of the breakthroughs for this material. We are a public company, so I have a forward-looking statement and advisory. So I have a forward-looking statement kind of the advisory, and so Coal Plants, at its core, is focusing on developing innovative materials for medical aesthetics, tissue engineering, tissue regeneration and organ manufacturing.
Speaker 2:The core product that we focus on and that we initially developed is a recombinant collagen produced from genetically engineered tobacco plants. So it's a type 1 collagen. It's bioidentical to human collagen but produced through these genetically modified tobacco plants. We have a large strategic agreement with Abbey that you might have seen and I'll share some work that we've done with them. And again, we're a publicly listed company. Now most people on this call understand why we are focusing on collagen.
Speaker 2:If we are trying to bioprint or tissue engineer organs, tissues, scaffolds found within the human body, well, collagen being the most abundant protein and a structural protein found in the body, is it makes sense for that to be the key contributor and the key material used for bioprinting. It's a natural scaffold. Cells are naturally surrounded by collagen almost everywhere in the body, and so we started with collagen. Now I mentioned we genetically modified the tobacco leaf and so the tobacco produces five genes the collagen alpha-1 chain, the alpha-2 chain and the P4 alpha, p4, beta and LH3. And so when we combine all of those, we end up with a full-length pro-collagen triple helix type 1 collagen. We then go through the extraction and purification processes and yield a type 1 atylo collagen with the triple helix form. And again this is based off of the human sequence.
Speaker 2:Now, because we're talking about tissue engineering, the normal, just plain type 1 collagen has some drawbacks. If we are trying to think about large organ manufacturing, it needs something that's going to be more robust, durable and have stronger elements of cross-linking, and so colplant, methacrylated that collagen. And what I think is fascinating about this material is that, first off, it's xeno-free, animal-free. All the components we used were xeno-animal-free to produce the material, which is really big in today's day and age, With the NIH coming out and really trying to push research away from animal models and more towards these xenofree platforms. Another thing I like about this material is that for DLP and extrusion-based printing it does not gel at room temperature, so you don't have to worry about the viscosity or rheology shearing properties changing over time as you're trying to print with it.
Speaker 2:And then for me, the two most important features is that with other kind of animal-derived materials it is, once you're above, about 8 milligrams per milliliter of concentration. It gets very viscous, very difficult to handle, and it starts polymerizing above 15 degrees C and so it clogs needles, it gels, it gets opaque, which reduces light penetration for DLD imprinting and you also have kind of this cap, around 40 to 50% methacrylation. When it comes to collagen, it's kind of difficult to get higher than that. Now, what I love about this material is that we can solubilize it up to about 22 milligrams per milliliter concentration and we have a version that's 90% methacrylated. So when it comes to tissue engineering, if you want something to cross-link faster or be stronger or degrade slower, we can use this material to create something about almost three times more concentrated and twice as methacrylated than other collagen-based materials. And so it gives you a lot more of this tunability and really flexibility to play with this material and customize it to work for your application. And so here's a some rheology data showing just 20 seconds of cross-linking with these materials gets it up to, you know, a thousand or ten thousand pascals, and this is only at the 10 milligram per milliliter concentration. And so, again, with higher concentrations, higher with that correlation rates, you can really frost link things quickly and create robust materials or you can tune them to be slower, softer, degrade faster, whatever works for your specific application.
Speaker 2:Here's a video of you know we want to talk about tissue engineering, right, and we're kind of a medical aesthetics-focused company in tissue and organs, and so here's a video of DLP printing. You know, photocross-linking the methacrylated collagen to print a breast implant with the methacrylated collagen. This video it's about a 45-minute process. I believe that we've obviously sped up, but you can see a very robust, porous, large scaffold that can be 3D printed. Now this material does have some other polymers in there to increase, but not for the cross-linking aspect. It has some additional polymers for the actual flexibility of the material. When you think of the various requirements for a breast implant, for a mastectomy patient, for example, there are certain durability, flexibility requirements, but the cross-linking is coming from the methacrylated recombinant collagen, and so this is a really cool breakthrough. Again, it's stable at room temperature, which allows you to do these longer DLP prints for bigger constructs, and it's strong enough and durable enough to withstand that process.
Speaker 2:So with this particular implant, we implanted it in an animal study and you can see here the white is regenerated or new tissue, and so when you implant the scaffold because it's collagen cells will attach to it. They can migrate across it and invade it, compared to like a silicone scaffold or a silicone implant. And so within a couple months you can see a lot of natural tissue regenerated and grown within the scaffold. We've seen blood vessels penetrating throughout the implant and then new vasculature and blood flow, new vasculature and blood flow, and then after that there's an explant study just to kind of validate the results that we're seeing of generated vasculature, blood flow throughout the scaffold, and so that's very promising results. Again, it's attributed to the fact that it is a collagen-based scaffold. That's just very natural and native to the body, and because it's a human collagen, you don't get that rejection of the immunogenic response with another collaboration.
Speaker 2:This is a trachea scaffold that was printed. I like to include this one because it's it's a larger scaffold, um, but you know, higher resolution, you can really see the details. And then another beautiful thing is okay. Well, let's take, you know, the body doesn't just have collagen, right, we want to make the. Let's say, we want to print something that's as physiologically relevant as possible.
Speaker 2:Well, you're probably going to want to add in something like hyaluronic acid, because that's very prevalent as well, and so when we add in hyaluronic acid, you get these materials that have the strength from the collagen but a little bit more elasticity and flexibility, kind of this squishiness factor that the HA contributes, and so you can really dose in different materials, because every single tissue is different. There's never going to be this universal bio-ink that fits every application, because every tissue has different stiffnesses, different cell types, different layers, and so being able to combine the collagen with other materials is necessary for really creating organs and tissues that fit your applications. Again, another example of you know, let's change up the formulation a little bit and end up with something that's very flexible and squishy compared to something that's maybe a little bit more robust, maybe something that it grades slower over time in the body, something that bounces differently Depending on what you're working on. So it's a tunable material. We're making great strides at Coal Plant focused on the tissue engineering space, the organ manufacturing space, and my role at Coal Plant is really to help get these materials into all of the labs in the US, North America, around the world all of the labs in the US, north America, around the world, to allow everyone to get their hands on and start really playing with this material and pushing the limits and pushing the boundaries of what can be printed DLP, printed two-photon, extrusion, stereolithography, acoustic what can be done with these types of materials and what kind of breakthroughs we can continue to make, all of us together.
Speaker 2:Again, cell attachments. I think this is my last slide but obviously, because it's a collagen material, cells love to attach to it, both within the material, like a spheroid on top of a printed disc, or you can see the beautiful striations or beautiful attachment across a printed forest scaffold. And again, it's an honor to be working with this collagen material. I was working with collagen for the last 10 years, so I'm grateful to be working with the coal plant collagen. And if you want to reach out to me directly, you can find me on LinkedIn, bowman Bagley, or you can send me an email, bowman at coalplantcom. I'm happy to just talk about your application, learn about what you're doing and see if there's a way that this methacrylated recombinant type 1 human collagen can work for you. Thank you.
Speaker 1:Thank you, Bowman, Beautiful presentation. Okay everybody, if you have questions for Bowman, please enter them into the QA box, because I'm the one woman show here. So my first question is even though this is genetically engineered material, it still somewhat is growing in nature. How do you guys keep the consistency and quality of the material produced?
Speaker 2:That's a great question. I want to see if I have someone on my team in here, but I can answer most of these. So the materials are produced under, under iso. We have very strict quality standards. Um, there's a there's a really cool video that's, that's on youtube right now that actually shows, you know they, they have clamps on the leaves to ensure the proper temperatures and the proper environment and growing environment for the tobacco leaves. You know, and just and just that level of quality assurance and QAQC that they're doing all the way down to the leaf through the whole process. And then we have two materials that are CE marked in Europe using the core collagen material, and so they've done all sorts of quality tests to ensure consistency from batch to batch. You know product viability, all that. So they have really good quality standards in place. Um, and it's yeah, it's a good material okay, we have one question from the audience.
Speaker 2:Um, let's see how do you cross-link this material so the meth methacrylated material is going to act like any, you know, gelma, hama, any of those types of methacrylated materials. So you include a photo initiator and use a light source.
Speaker 1:Okay, another question from the audience Amazing talk From AstroHealth's perspective. Are there any opportunities for copeland technology to support regenerative strategies in space environment like micro? Yeah well, microgravity radiation exposed environment. Um any radiation studies done so far?
Speaker 2:great question specific yeah very specific question, but a great question nonetheless. I'm relatively new, so I don't have the full history of what Coldpoint has or hasn't done, but I have already been in talks with a company that routinely sends various experiments and materials up to space for these types of studies, and so my particular role. I'm open to any of those types of collaborations and exploring and discussing them, and that particular thing is something that I've already had a conversation about, but I do not know for sure if it's something that they have or have not done already.
Speaker 1:Yeah, very interesting question indeed. I mean, if anything, a lot of times it's easier actually to do things in space when you remove gravity than not. So things are different up there. All right, thank you so much, bowman. That was a fantastic presentation. I'll just check if there's anyone else who's putting a question. Oh, there's another question. Okay, which plants are most promising for collagen synthesis? Well, I think they said it's tobacco. Why tobacco?
Speaker 2:actually the one that we're using is the tobacco leaf.
Speaker 1:Yeah, wine, tobacco.
Speaker 2:The research was done about 20 years ago at a university lab and they spun it out to create coal plants. So I would love to meet the founder and dive deeper with him and learn about that. But the tobacco leaf seemed to work and be consistent, and the company is founded and based out of Israel, and so there might be some elements of certain geographical requirements. Yes, that's what.
Speaker 1:I'm guessing.
Speaker 2:But the one that we're using is tobacco leaf.
Speaker 1:Actually I have a question I forgot to ask you. It's like, how do we know this is human collagen and not other collagen? And two is whose genetics were used? I mean, is one individual's collagen for everybody, or does it matter?
Speaker 2:That's a great question and I don't have the exact answer to that.
Speaker 1:Great, we have some mysteries to solve. So, bowman, you're free to put your email and your contact links and your LinkedIn in the chat box, so people who are here live can immediately connect to you.
Speaker 2:I will do that, thank you.
Speaker 1:Okay, thanks. Okay, we're going to move on. This is rapid pace here. We're going to move on to our next speaker, ms Janina Janelczyk. I hope I did that right. I think I'm a little bit. Yeah, we need to talk about your family, because you have a history of science in your family, janaina. All right, please take it away from here.
Speaker 4:Can you see my screen? Yes, let's go. Hello everyone, I am Janaina Deroseki and I'd like to thank you, jenny, for this opportunity. I'm so happy to be here to talk about this field and share my studies. Well, I am co-founder of CO2 Quintus. I am also a geneticist and during my PhD I studied microRNA Yostesis, bone induction with microarrays and mRNA interference. After my PhD, I studied in my postdoc a separate bioprint methodology, so let's start talking about advanced biomaterials.
Speaker 4:I'd like to go straight to the point why we are producing human extracellular matrix from human 3D tissues. It was a funny history. My partner, Diogo, challenged me a long time ago if I would keep teaching instead of doing something that impacted the world. I told him of course I will continue teaching, but also I will do other things that impact the society, and that's how Quentin was born. I start my presentation to ask what is the main problem that we are addressing Today?
Speaker 4:The estimated cost of treatment on patients waiting for an organ transplant in the world is almost $2 trillion. The main treatment solution for tissue damage by aging, trauma or implants is made with biocompatible synthetic or animal-based materials. With the advance of cell therapies and biofabrication, this appears to be taking a different direction. New technologies open up new opportunities for the development of advanced biomaterials. Of course that we should be concerned about this issue. What makes a good biomaterial for medicine to restore tissues organically? We showed you understand that biocompatibility, printability, bioactivity, scalability and reproducibility are the core requirements for advanced biomaterials in bioprinting and the other fields in tissue engineering. At QANTIS we address these challenges by using extracellular matrix ECM models as inspirers for our biomaterial design. This approach allows us to create bioengineered solutions that support cell survival, provide structural stability and deliver the biochemical signal needed to guide tissue regeneration at the cellular and molecular levels.
Speaker 4:Here I bring some characteristics that polymers, hydrogels and ECM present. All of them are important for us, but when we're talking about production, we are thinking in hybrid hydrogels or solutions. In this case we combine different molecules to achieve better mechanical properties, enhance the biological functions, immunological signaling and scalable process to have solutions with better cost benefits. But let's talk about our platform. The name is Quantum Tissue Platform and we patent the process and not the ECM solution. After lectures about biofabrication in general in my journey I felt the need to think in new biomaterials for humans without animal source. Over the past five years we have developed the Quotidish platform, leaving by engineering the system that goes beyond standard bioreactors by producing real human ECM with complete fidelity. We are in Brazil, inside the bio industry, with our laboratory. I'd like to explain a little bit more about our platform.
Speaker 4:We use certified cells and initiate a cell replication process. We add the cells to biomaterials to prepare our bio-wink, specifically bio-wink. This bio-wink is loaded into the bioprinters, simple bioprinters, which, layer by layer, build our derm-like tissue. Over six days, these 3D tissues produce collagen and the other proteins such as elastin, fibronectin and glyphosamine glycans itself. After that, homogenization and extraction process without the use of enzymes is performed and each final value of Q-matrix is collected and quantified. This final solution is our Q-matrix and, quantified, this final solution is our Q-matrix. It is important to highlight that known antibodies are used in our process. In this new process you can tend the cells to produce other types of ECM, for example, using osteoblasts to produce bone ECM and chondroblast to produce cartilage ECM. It's possible here.
Speaker 4:I'm sharing some images from our platform. First, you expand human primary cells. After that we produce ischeroids to build 3D tissues. Here like dermal-like tissues that functional as a bioreactor. It's not a bioreactor, but it's like. In the third image we show proteins and in red we demonstrate the presence of type 1 collagen. In the last image we can show the complex network that Q matrix represents. I included an image of lyophilized Q-matrix here.
Speaker 4:Q-matrix is not just another biomaterial, it is human extracellular matrix biofabricated for the first time, scalable when we compare with other 2D cutters or with 2D cutters inversatile for tissue regeneration. With a solution like this, we can produce several products in medicine and aesthetics. We obtain SLOR, ecm-contained intact proteins without degradation because we don't use enzymes Through an entirely animal-free process. We do not use proteins from animal sources and the platform provides regenerative functionality while being sustainable. Since all cells are recyclable in our platform, how can Q-Matrix help in regeneration?
Speaker 4:In this image, through a scanner electron microscope, we can observe important microstructures similar to those found in natural tissues. We see pores that are favorable for cell migration and interaction that are favorable for cell migration and interaction. Behind the pores there is also a complex network of large and small fibers which are crucial for cell adhesion and differentiation. Importantly, q-matrix is not composed of collagen alone. It also contains glycosaminoglycans, elastin, fibrinatin and a small amount of type 3 collagen. This unique composition makes it highly effective in mimicking natural tissues and supports regenerative models.
Speaker 4:Here I present some results. Archeomatrix can be used in various ways, such as for the production of an artificial skin, in vitro models, scaffold for 3D culture or collagen coating for cell culture, with the key advantage of being bioidentical to the natural hormone ECM. I'd like to raise two questions to streamline reflection on cell culture work. Which of them do you find most interesting or relevant for your work? Do you use any type of collagen or ECM in these steps? So in some cases we can apply ECM as an additive to study cells, spheroids, bioinks and tissues in general in a different way, often needing to surprise the results, and in this graph, at 80 micrograms per ml, we observe 120% cell viability compared to the culture medium, to the control In this slide.
Speaker 4:We used 3D skin models with cuts. We did cuts to study the rate of fibroblast proliferation and after 24 hours we observed intensive regions of fibroblast proliferation. Quants is able to overcome all the key characteristics of dermal and joint injectable, such as support, bio-stimulation, bio-identical materials and tissue regeneration. In addition, this new generation of collagen fillers offers no adverse reactions due to a poor process and a regenerative effect. When we compared the Q-Matrix solution with commercial brands available on the market. We found that Q-Matrix stimulates fibroblast proliferation instead of causing cell mortality, as some anesthetic products to do, bio-stimulate collagen production. In this case, we are demonstrating that your ECM promotes new collagen production through fibroblast proliferation, not through inflammation. To conclude some of our studies in recent months we have been working with bone scaffolds and Q-matrix, comparing them with red collagen. We are conducting several tests with partners in the dental industry and I would like to highlight that the combination of polymers, ceramics, bioglasses and the other materials in this field can and should be integrated with advanced biomaterials to enhance their functionality and improve the quality of the bone and cartilage produced. We expect big progress in this field with the arrival of new, more bioactivity scaffolds.
Speaker 4:Currently, many biomaterials are used to regenerate and restore the structure and biological function of damaged tissues. However, we must all consider that physicians and patients need to easily understand and apply new biotechnological solutions, including minimally invasive processes capable of regenerating all tissues. I leave here a reflection the simplest solution often heals the most. Where is Qantas in its development journey? From lab validation to preclinical and clinical studies, scanning with industry partners and regulatory alignment? In Brazil and the other countries, q-matrix for R&D is possible. We sold some samples for cosmetic industry, universities and the other areas, but only R&D.
Speaker 4:We are developing a new generation of regenerative human tissues, not just to feel, but to truly reconstruct damaged skin and tissues. In five years we aim to support dental cartilage and bone care with innovative human biomaterials enabling the development of new hydrogels, membranes, cements, glues, scaffolds and other tissue solutions. We are a team of scientists and engineers using biofabrication to shape the future of human regeneration with new human materials. I would like to thank my team here and, to conclude my presentation, I'd like to thank you once again and say that I'm open to connecting with everyone. You can simply send me an email or add me on social media. I'm happy to answer any questions. Thank you.
Speaker 1:Thank you so much. Wow, amazing presentation. Thank you so much. Okay, everybody, if you have any questions, please put them in the Q&A box. We have a couple minutes for Janaina to answer. I'm going to start with mine. It sounds like your bio ink, or your material, is tunable as well. Question is how do you manage? You know the composition, since, like you know, this is, it seems like it's a composite rather than a single material in your final product well about your ibar material that I put in my platform, or the final, the platform, okay yeah yeah, well, I use some polymers, synthetic poly polymers and with thermosensitive characteristics, and because these I don't use enzymes and at the end I separate the cells and the ECM produces.
Speaker 2:Okay.
Speaker 4:So because this is more easy to collect this ECM to produce bioethics, okay, it's beneficial. I don't know if I answered.
Speaker 1:Yes, and then how do you make sure that your final material is what you really want?
Speaker 4:I analyze it with Western blood and other types of tests to prove that I have collagen, elastin, fibronectin and gagisominoglicans. So I have to do some kind of testes to prove this.
Speaker 1:Okay, great. And then it sounds like you guys are in preclinical phase with the skin regeneration product. This is a bioprinted skin product or this is just a regular aesthetics trials?
Speaker 4:So great, great question. Investor asked me a lot about this. So our final product is only proteins, only big proteins, and because of this we have a device, a medical device, and not a biological product. Because we have only proteins and it's more easy to go to market. Because I don't have 3D tissues, I don't have cells, I have a cellular solution of ECM.
Speaker 1:Got it. Okay, great, okay. Thank you so much for the presentation. So, everyone, in terms of the recording of this presentation, it will be on demand on zoom. So, where you are right now, you can just come back after the end of this presentation and you can watch it. To answer a question from the audience here okay, let me see we have a question in the qa box. Great, great presentation. Have you performed any research with regards to 3D tissue models for preclinical studies, in particular related to autoinjectors or needle-based injection system characterization? That's a very specific question. I don't really.
Speaker 4:I think it's above me.
Speaker 1:Yes, I don't know. Let me just think twice what that means. Autoinjectors or needle-based injection systems I don't know what that is. I don't know. Scheme models Well, I think we just talked about that. Luciano, maybe we're not understanding your question perfectly. You feel free to contact Junaida about this. You feel free to contact Junaida about this. And the other question I have for you is if a startup or a lab wants to work with you, what is the normal process of collaboration? Let's just say if the lab or startup is not in Brazil, it's somewhere else.
Speaker 4:I have some collaborators in Europe and Germany and I'm at RECM in some projects, in some master and PhD projects, and I think that the next few years I will have more results about these collaborations.
Speaker 1:Okay, great, and so you can ship your material. Mm-hmm. Okay, so it's not locally produced, but you can actually directly ship. Yes, I ship it. Okay, great, all right. Well, thank you so much. We're going to move on to the next speaker, but we'll invite you back for our final discussion. Next speaker is Professor Ricardo Lovato, who is very well known in the space of biomaterials. Please take it away, ricardo.
Speaker 5:Thank you, jamie, thanks for the kind introduction and thanks everybody for joining this fantastic event. I will change a little bit pace because I will dig a bit more into fundamental research as of what we do in the lab, but with a clear focus on different materials and how we can use them indeed for biofabrication and I hope you can all see my screen. If not, please let me know A brief introduction. I'm from Utrecht University where, in my lab, we focus specifically on developing different biofabrication technologies, with a strong focus on light-based printing techniques, as you will see today. But, as also was said earlier today, without materials there is no printing. So it's really fundamental that we have the right tools, the right biomaterials, the right bio-inks that we can then use to create different structures for capturing cells, and not only for keeping high-shape fidelity, but also for letting cells do what they know how to do best, which is reorganize the matrix and produce new tissue as well, and for that we use both commercial materials and some lab-made ones. As you will see soon, we focus on application primarily in vascular biology, as well as soft tissue engineering, such as the pancreas and the liver, and the technology I will talk about today for those that don't know it yet, it has been around already for six years what we call volumetric bioprinting. For those that don't know it yet, it has been around already for six years. What we call volumetric bioprinting, and what you see here running in this slide, is actually a real-time video of a print where you will see appearing, now in the middle of this field of view, the tower of the Cathedral of the Museum, which is the landmark of our city, and it's about after 12 seconds the object appears. So, for those that are not familiar with this technique yet, what's happening is that we have a photo. Responsive material could be your classic gel. Actually, the gel is a workhorse in our lab and we shine light onto it using a blue light laser that hits a digital micro-mirror device and sends the light on the middle of the vial. Now, with every angle of rotation of this rotating stage where the vial is placed, the image in the micro-mirror device changes and, by using tomographic algorithms, we reconstruct the object that we want to print by delivering higher doses in the voxel that we want to cross-link. So you stop the process, you wash out the unreacted material and you're left with your three-dimensional object.
Speaker 5:We have already applied this technique on different applications and when we first, very first, started, we started with Gelma and essentially to re-optimize a bit the concentration of initiators and the amount of cells that we can actually load into these systems in order to create these nice models of the trabecular bone. But we then moved on to softer tissues. For example, we printed liver organoids and we then showed how playing with the architecture of the print actually allows to boost the function of these organoids, in this case of performing vital liver function, for example, the elimination of toxic compounds like urea from the bloodstream or, in this case, the simulated blood that we inject in the in vitro model. As well, as we showed, you can actually combine these bioprinted materials with pre-made fibers of thermoplastic polymers like PCL to create sort of PCL stands with the lateral spinning, lateral writing and then print around the vascular structure, which we can also perfuse. And recently we've been focusing a lot on printing stem cell-derived islets. So we take induced pluripotent stem cells, we differentiate them into pancreatic islets and we print them into different shapes with a perfusible channel to keep high viability and use them as in vitro models for testing drugs against diabetes.
Speaker 5:However, a key challenge is to actually have materials that enable the formation of vasculature at all levels, so not only the ones we can print but also the capillaries that have to grow within the print as well. And I have a student, so my student in my team, maria, has been working with this vascular spheroid. But you have material cells and stromal cells as support. When you put them in the right matrix, this nice structure happens and they start connecting from the microvessels. With a big caveat what you see here is done in matrigin, and matrigin, first of all, is not printable, but that's not the biggest problem. But, as you all know, it's a very chemically undefined matrix, so it's derived from mouse tumors. So there is a lot of ethical problems, but also practical problems, because if your material is not reproducible, essentially your experiment one day will vary completely from the other day, and then it's very difficult to really identify important variables where your base material changes so much.
Speaker 5:So we went back to the drawing board and we took a very conventional gel mass gel to the metacrylate, and we thought can we keep it printable or even maybe improve the shared fidelity, the quality of our prints, while also allowing cell migration at the very high level? So we achieved that by introducing some supermolecular units. So we put adamantine, these purple boxes here, together with cyclodextrin, which is the drone here, as a bucket which basically permits a guest-host bond. That is completely reversible and the beauty of that is that basically it makes the gel microscopically stiffer. So now if we print these wheels, if we make it with normal gel, not 5% weight or volume, they collapse under their own weight. But with this material they are able to withstand their own weight and we can print them very nicely, but at the microscopic level, cell-level forces. Cells are able to break these bonds with minimal integrated stressors and therefore they can migrate and after they move on the gate closes back again, giving support to the structure. So basically we can combine a beautifully suitable micro-scale environment for cell with the macro-scale environment which allow stiffness and printability.
Speaker 5:And what you see here in green are endothelial cells that are populating a large print with very high migratory capacity. We can print these nice gyroids, as you can see here, and you can appreciate our, in this case, phalloid-instained cells. They can grow very nicely on the surface of the gyroid, but they can also populate the cross-section and stretch into it, as you can see from this confocal cut of the object and the nice aspect of that is, of course, when you do volumetric printing you start with relatively low cell densities, typically below 20 million cells per ml. But of course, since cells here can proliferate, you can reach physiological levels after a few days and weeks of culture. We also dig a bit more into the econobiology. For those that are interested, all this information is in the preprint which we have still on bioarchive at the moment.
Speaker 5:The paper is still under review and basically we see that the cells in our hybrid gel, as we call it, are not necessarily the most stretched compared to a gel with a low degree of functionalization, but they are the ones that have the highest activation of YAP, which is a marker of the carotransduction essentially. So the mechanical aspect of the cells breaking the bonds is what really drives migration here. And because we can now have a gel where cells migrate very nicely, we can try to think of assays where migration is especially important. And we team up with people at the oncology hospital here in Utrecht with a group of NREOs where they study immunotherapies and basically they had cut T cells, engineered T cells to kill tumors and we tested them in the ability to invade our gels when the gels are populated with the patient-derived breast cancer organoids which are here in yellow, with the patient-derived breast cancer organoids which are here in yellow. So when we put them in matter gel, matter gel actually inhibits T cell migration due to the high laminin content as two more derived matrix. After all, the gel is too stiff for the T cells to go in and you see, some of them have fallen around, but in an overnight experiment they barely go through the surface, whereas in our hybrid gel, when we start imaging, the cells are already invaded the gel and by the time the overnight experiment is gone they are swarming around the tumor and you will see the yellow tumor organoids disassembling and falling apart as they're being killed by these structures.
Speaker 5:So now, because we can print these gels, we can start thinking of 3D abscesses where we can investigate these gels. We can start thinking of 3D abscess where we can investigate their tumor targeting capacity in a more semi-realistic environment. So here we designed this breast cup where we have a porosity inside that mimics the ducts and we have spheroids of a healthy cell line populating all around and in a specific spot sealed in a breast cancer organoid. So when we add into the ports our engineer t cells. We can see if they actually go um off target so they go attack in the hip the cell t cells, or they can really find their way to the tumor and attack it. That's exactly what happens. So when we look at the tumor core here in this slice, we can see the blue uh, you stay in the air car t cells that are finding the tumor core and starting to attack it. As you can see from the red stained-ear in this last image is CAR TECA space tree, which means that the tumor cells are undergoing apoptosis due to the toxic effect of the T-cells. So thanks to this, we can now investigate different settings and we are quite excited about exploring these materials a bit further with different applications, but also to see if there are commercial partners to which we can perhaps bring these materials outside from our laboratory and more in the hands of more people besides us.
Speaker 5:Of course, in terms of materials, of course, besides printing itself, it's also important to control the chemistry of what we print. So we also investigated tricks to engraft growth factors, because typically in the matrix of our tissues it's not just a structural role, but the matrix also is a deposit for different types of morphogens and growth factors that lead tissue maturation, for different type of morphogens and growth factor that lead tissue maturation. So in this case, actually teaming up with partners in Brussels actually one of the founders of the company of Jasper, which you'll talk after me, which is Samblam and Bliberger, we worked together on this paper. We synthesized this D-gelatin norbornin, which of course can photocross-link in presence of of different dilated compounds, but can also be used to engraft compounds with cysteines. So essentially any, any protein.
Speaker 5:So what we do here, we first make a simple upper print and then we infuse the protein of interest and we do a secondary print that this time glues the growth factors in the path of the light and not everywhere else. So if you do things right, you see something like this, where you have in green the printed gel with the channel in the middle, and this red spiral here is not a physical object but is a trail of a growth factor where the chemistry of the material has been modified. The approach is quite high resolution. We can print very different type of patterns and geometries. We can reach about 50 micron resolution and the growth factors are still vital and functional after we glue them. As you see here, we print this channel with only one side with growth factors and in the middle with endothelial cells seated on. And only when the VEGF in this case vascoendoth agrotactone is grafted, we see the endothelial cells sprouting in and penetrating into the gel, whereas in the other region they just hit into the lumen without doing anything. And this is quite interesting because we can quantify it and see what happens there. But it's quite interesting to start also altering the chemistry of our materials to improve the mimicry of the native ECM and materials to improve the mimicry of the native ECM.
Speaker 5:And one last thing that I wanted to share with you is not necessarily materials related, but it's more on how we can actually change the way we print these materials. And it's all spun from the idea that tissues and organs of course their geometry. It's adapted to the function that they need to fulfill. However, printing is not exactly adaptive in the sense that we first decide, kind of a priori, the model we want to print. We prepare our bioresin or extrusion ink or whatever we need and then we superimpose inside the vial of our resin the design that we made, interrupting the cells a bit in a random way. So if you think of an example of creating blood vessels, you will have some vessels that are going close to the cells of spheroids of interest and some that are pretty far, so you may not have ideal viability there.
Speaker 5:So with SAMI we thought if we can sort of teach our printers to see and also to design together with us, to improve the quality of our print design as well. So we paired the printer with a light sheet imaging so that we can scan the different cells or spheroids that are present in that, use some computer vision tools to create a registration map of where these spheroids are and then ask the printer to generate automatically by itself a design, for example a vascular design where a vessel fits every spheroid that we embedded in our resin. The live sheet scanning and basically, as I mentioned before, this is tripodated to imaging information which then is used to create the different designs. And we can also ask the printer to change the design parameter according to, for example, for S-men, stains that we include in the spheroids or a geometrical consideration that we may have, and the printer generates the paths for the actual printing. Finally, perform the classic volumetric printing with its optimized design and we end up adding the feature of interest.
Speaker 5:In real life it looks a bit like that. So this is a scan of the printed part and the paper, by the way, was just published yesterday, so feel free to it's open access, so feel free to go and check all the details in there. And you see here how every sphere which are in false colors are actually wrapped by these capillary networks. We can set some rules, as I mentioned before, in terms of geometry, size or colors. So fluorescent staining and, of course, besides vessels, you can also encapsulate your spheroids, connect them, but also do multi-material prints so that we can actually print the first material, in this case the bone-like material, and then have the cartilage fully automatically align on top of it.
Speaker 5:Just a quick run on an example of functionality. So why should we even bother doing all of this? We made some gels where we have some rings of pancreatic cells and there we asked the printer to either make no channels, make some random channels, or optimize the design of channels wrapping around this ring, with the rule that the surface area of the channels should be the same across all samples to have the same capacity to exchange solutes. This is a bit of what it looks like now after we do a rendering or a fluorescent imaging of the structure, but this is, of course, cross-sections and indeed there is a benefit in that. Of course, the optimized vascular parameters give a higher insulin secretion compared to the others, indicating that it gives better nutrients while help, of course, the cells to perform better.
Speaker 5:As I mentioned, we can also use this approach, which we call GRACE, which stands for Generative, context-aware, adaptive Volumetric Printing. Basically, we have, we can do some multi-material prints here. We have the first print with an ink that contains bone cells the ink is gel in this case and then with an ink that contains cartilage cells and when you culture them long enough in the right media, you get mineralization in the bony part, as you can also appreciate in this histological staining. The brown here the bone cost indicates calcium deposits, whereas the red here indicates the cartilage region, indicates because of aminoglycans, showing that the two cells are differentiating into the right path.
Speaker 5:Now, I talked a lot about this for metric printing, but of course I don't think that's a magic bullet that will solve all the problems of biofabrication. We actually need most likely every technology for a different application. Oftentimes we need to combine technologies together. But as you can see from this example, materials are vital because you can print any shape you want, but if your material doesn't match the application or the need of the cells you need to use, there is very little left to do. So, indeed, we need to combine all these things advanced design, printing, relevant materials in order to create fully biofabricated implants for clinical application, as well as for preclinical study and drug investigation studies, for example. With that, I'd like to conclude. I'm happy to thank you for your attention and take any questions you may have, and take the chance to advertise that we are hiring one PhD and one postdoc, so feel free to reach out via email or social media if you are interested. Thank you.
Speaker 1:Thank you so much. If I'm a student, I would join your lab in a sec. Also, Professor, feel free to put the paper that just got published in the chat box so people can download as well. Thank you so much for presenting the results. We have a couple of questions from the audience. Let me take a look. Let's see. Okay, one question from Alina. What is the main advantage of using the volumetric bioprinting technique compared to established other types of printing technologies?
Speaker 5:So one key advantage, of course, is speed. So in the very first study what we showed is that, especially when you want to create something that is several centimeters in size and centimeter cubes, you can make it in 10, 20 seconds with this technology. But with extrusion or DLP it scales up considerably. With DLP it scales linearly with the height. With extrusion it scales with the complexity of every layer as well with the height with extrusion, in scales with the complexity of every layer as well. So about four centimeter cubes can take up to a couple of hours with extrusion, If you have a decent resolution, of course, with this technique will take 20 seconds. That's, of course, a clear advantage.
Speaker 5:Another advantage is the freedom of design. You can make very complex geometries without the need of supports or suspension buds or anything like that, which is a key advantage. That being said, there is a limitation on the density of cells you can load at the beginning. With extrusion you have essentially nearly no limitation. You could have a 90 percent of the volume of your ink made by cells potentially. So you could go very high here in this case, and you need light to diffuse freely, operate freely inside the volume. So when you go very high in sub-density you start having scattering events, so typically we don't print more than 20 million cells per ml that totally makes sense.
Speaker 1:Thank you so much for the explanation. All right, we have another question from Gabriela I would like to know regarding microvessel production Is sprouting stimulated under static or dynamic conditions, and for how long do microvessels remain stable and perfusable?
Speaker 5:Right. So this experiment is static, and that's a very important point, Because if you do it in a static condition, after at best, 10 days, they start regressing the microvessels because they need flow. They need flow to keep the lumen open and patterned If you. However, we have started in the recent months to actually do active perfusion experiments and there you can see, you can keep them open for several weeks, but you do need perfusion, Otherwise the vessels will regress and disassemble.
Speaker 1:Okay, thank you so much. I have a question about the multi-material that you mentioned. I'm just kind of curious how you accomplished several different materials in one print. Is it because you change the ink in between, so you have to take the thing out and then do it? You have to do it twice.
Speaker 5:Yes, sorry, I didn't explain it very well, but indeed it's a sequential process. You first print material A, you wash out the erected material, you have the printed part, you put it back into the printer and load the second, second material and then do the secondary print on top of it. The advantage of the grace approach is that you don't need to align manually your printer, your, your printed object to the light projections, because the print does it for you. The printer finds the orientation in which you place your uh, your part and then automatically prints on top of it or around it, whatever you. The printer finds the orientation in which you place your uh, your part and then automatically prints on top of it or around it, whatever you need I got it okay.
Speaker 1:Um, I have another question is um, you know, I I love the adaptive bioprinting process you just introduced as very innovative concept to me personally. Um, just maybe a little bit of philosophical question is um, what do you think it's have you guys done? Or scientific question is have you just, you know, did a comparison of micro vessels or micro vasculatures that's naturally generated from the original, you know bigger print versus the designed vessels by computers? Have you guys decided, you, you guys figured out what's better?
Speaker 5:It's a fair point. We have not done any comparison there, but I think to some extent you need both. Right, because you need the printed vessels, but you also need the cells to make the capillaries, because of course, there is a limit in terms of resolution with what we can print. We can print down to about 200 micrometers to have open channels. Anything smaller than that has to come at the moment from endothelial cell self-assembly. So you need both and you need to anastomose, and there is some fantastic work from the group of Shula and Mittle-Eleven that shows that in the context of extrusion printing. But you need to have both approaches there. Of course, you could potentially print capillaries with technologies like two photon, and I believe that jasper will talk a bit about this technology later. Yeah, um, but of course at that point, uh, with two photon, going to large volumes becomes very challenging and you can argue whether you really need to print every single capillary or you can just rely on the ability of cells to make their own job, of course.
Speaker 1:Yeah, I think that's actually my question. Do you need to print every single capillary? Probably not.
Speaker 5:But I mean it may be an approach right, it depends on your question. I mean maybe an approach right If your question it depends on your question. If your question is, I want a capillary that has this specific geometry and I want to investigate, for example, some vascular pathology where the geometry is very important. And then the question yeah, maybe you have to print it, but if you want to do a structure where everything is vascularized, maybe the best approach is actually to take the best of both worlds. So have the larger vessels printed and the smallest one formed by the salesmen themselves.
Speaker 1:That makes total sense. Thank you so much, professor. I'm going to move on to the next speaker, since we have quite a few content still coming up. Next speaker is Jasper van Horik, who is the CEO of BioInks.
Speaker 3:All right, let me share my screen. Okay, all right, can you see my screen, I assume? So, yes, okay, perfect, hi everyone, I'm here to talk today about bio-inks and, more specifically, the materials related to bioprinting, but I always like to start with sort of an analogy, and the analogy I always like to draw is the analogy with classic cars. You can keep a car running forever if you have the right spare parts, but, of course, for humans, the situation is not there. So what if we could 3D print the spare parts? And that's actually why I was originally inspired to pursue a career in this field Like, what if we one day could actually generate these organs or spare parts? Is it science fiction or is it science? Um, well, I'm already the fourth speaker, so I I don't think I need to tell anybody anymore that it is science, but the concept behind it is is quite straightforward. Um, actually, because, um, the idea is that you, you would take your cells, uh, you put them into a 3d printer and basically, as he got also showed you, you put in your model of your tissue you want to print. You print your cells in the shape, you put it in culture and afterwards you can implant it. Of course, this is the theory. Practice is a lot more difficult, because cells are very difficult to manipulate and one thing which is crucial if you want to 3d print cells is that you need to have proper functioning materials. But, of course, if you think about most 3d printing materials, um, they're not really suitable for it. The conventional 3d printing materials at least, um, and also this is the case, or this has been the case for a long time, for for bioinks if, if you look at materials which would be suitable, often they are not ideal. And what I want to focus on, especially in bio-inks is often, especially in academic bio-inks is that there's poor standardization and that most bioprinting technologies just don't possess the right resolution for the right tissue architecture and function.
Speaker 3:And this brings us to what I like to refer to as the biofabrication deception, because in a lot of cases you have researchers which have very nice research in 2D and Petri dishes and then they want to transfer it in 3D and they read a paper about 3D bioprinting. So they buy a bioprinter, they make some materials or they get some materials and they want to start working. They just want to convert it to 3D and get what doesn't work. And why is that? Why is often the reason that it doesn't work? Well, there's multiple reasons. First reason is often reproducibility of the applied materials. Especially if they're made in their own lab, they may not have the right expertise. Second thing is in publications, of course, only the successes are reported. It's not published how many trials it took or how much optimization it took to make a certain material printable. And the third thing, which was also already mentioned by Ricardo, is there's often a mismatch between expectations and reality. There's not one printing technology which fits all. So in a lot of cases they buy one bioprinting bioprinter and they expect the, the potential of all the bioprinters, uh and. And then they want to print, for example, something in the resolution which is not not feasible. Um, and this is even more exemplified if you look at the, the one of the most popular materials, also mentioned by Ricardo, elma, which was originally developed in the research group where we spun out from. But if you look at publication of ELMA and you see what everybody is doing, you see that every lab does something different degrees of substitution, different concentrations, different photoinitiators, different solvents, which leads to poor reproducibility and, as a consequence, often perceived poor reproducibility of gelatin or bioinks and further fuels this biofabrication deception that it becomes tricky. So it's very clear that we should do something about it.
Speaker 3:And, if you ask me, there's a need for standardization in materials, because they are what's driving the field. And that's why we launched the company BioInks. We launched it three years ago as a spin-out from Kent University and the Free University of Brussels, spin-out from the research group of Professor Sandra van Vlietbeker, who was also already mentioned by Ricardo, research group of Professor Sandra van Vlietbergen, who was also already mentioned by Ricardo. And well, we launched this company because we have a vision that I think this is a vision which everybody here shares that one day you will be able to go to the hospital and get new tissues 3D printed using your own patient-specific cells. But, of course, it will not happen automatically. And one thing which is key there is to provide reproducible, standardized, high-performing materials to make the technology turnkey, because the goal to clinics is reproducibility and standardization and ease of use.
Speaker 3:And so why did we focus on this? Well, we had already some assets in our lab. We were, as I mentioned. Our lab is the lab where Jelma was invented 25 years ago, or actually this year celebrating the 25th anniversary of Jelma. It was originally developed in the PhD of Ann van den Bulcke, who is currently still a business developer and supported us with the spin-off creation of the current uh company, um. So we have this asset. We have a very experienced team uh founding team, of which we have over 150 papers. Between us have a lot of know-how on materials, um formulations, processing and things like that, which allowed us to generate an entire portfolio of materials.
Speaker 3:Again, as he kind of said, you cannot have one printing technology for everything. So we made different inks for different printing technologies, going from low-resolution extrusion all the way to very high-resolution multi-photonetography or two-photon polarization. But what we very strongly believe in what's already was also exemplified by Ricardo and also by Bowman is that light is probably going to be the way to go, which brings us to the company slogan of from light to life is the way to go because with, for example, this technology to photon polymerization, this laser based high resolution printing technology, uh, you can print down to subcellular dimensions, um. We can print down to one micron uh, even in the presence of living cells, uh. So that's one thing why we believe light is the future.
Speaker 3:The second thing, also already mentioned by ricardo, is. The second thing, also already mentioned by Ricardo, is scalability. Speed is just a lot faster in comparison to the to the other technologies and a lot more reproducible. So, on our quest to make this by fabrication technology, turnkey, the materials is one thing, but also the materials they need to act very well with the hardware. So therefore, we also partner up with different printing companies like Upnano and Nanoscribe, market leaders in the field of two-photon polymerization equipment, bajama 3D, felix Printers, extrusion manufacturers, sherdine, also making extrusion printheads, and then, more recently, carahoot hood, one of the? Um biggest gelatin, biggest chemical suppliers in the world. So that's downstream, but upstream it's also very important because, as I mentioned, standardization is key. So we also have a close partnership with rusulo, the biggest manufacturer of of gelatin, and, because we have these collaborations with husolo, raw material suppliers of gelatin. And then they are at hand the printing hardware.
Speaker 3:Uh, this further builds on our vision make the technology and print. So making it as easy as putting the materials in the printer, putting yourselves in there and start printing, and we have a few um different materials in this respect. Um, so different printing technologies. Uh, and I will just highlight some of of of our exciting materials um, one of them for digital light protection. So light based printing again, is the grassings.
Speaker 3:This is a polyester, very biocompatible. You can, you can see itself on there and here you can actually uh appreciate the resolution. You canible, you can, you can see itself on there and here you can actually appreciate the resolution you can obtain, as you can see that you can see the individual pixels of the of the projector and the cells growing on top of it. But what's really interesting on this material is that have shaped memory properties. So actually what you can do is you can 3D print a complicated shape. You can then heat it up, deform the shape and as long as you keep it below body temperature, it will maintain this temporary shape. So, as you can see here, if we dip it in 5 degree water, nothing really happens. But if you take it up to body temperature, it goes back to the originally 3D printed, more complicated shape, which makes it interesting for implantation, approaches it up to to body temperature. It goes back to the originally 3d printed, more complicated shape, which makes it interesting for um, for implantation, uh, approaches um, uh, where you would, for example, want something to unfold upon the body temperature.
Speaker 3:Another material we have for a different printing technology. So for for this, um, high resolution proton polarization is one of our hydrogel materials, hydrotech inks, and I think here you can see what the performance is of this technology and it made tremendous strides there. We can print from micrometer-scale structures up to centimeter-scale structures, but, as also already mentioned by Ricardo, of course it takes a while to print, depending also on the field of view. If you can still stay in the same field of view, it goes relatively fast because you print through a microscope objective. But the moment you have to start stitching it can become quite long to print bigger structures. And therefore we also are working on this volumetric printing. So we also have materials for this volumetric printing. So we also have materials for this volumetric printing.
Speaker 3:We have this gelma-based resin that we developed and here although Ricardo already gave plenty of examples of the performance of this technology, but here as well you can see a live printing process in one of our gelatin resins for Pi Day and you can see the letter Pi coming appearing. And this is real time. It only takes a few seconds. You develop it and you have your structure. And because it's so fast it has incredible self-viability. And since this technology is so fast. It actually opens up the idea that one day you could have this technology inside the operating theater, that you would have a bioprinter inside the operating room where you could, during a surgery, take out the patient's cells, take out the damaged tissue, print your construct and place it back in. So of course this is still a vision for the future. But the technology is getting there and the materials cannot lag behind. So it's important to have the right medical grade materials and therefore we partnered up with Rousselot using their ex-pure, endotoxin-free gelatin-based materials, which we also launched our first medical-grade extrusion-based ink.
Speaker 3:This is all materials, but of course it's the applications which make it interesting, and these different materials can all be used for different applications which, for example, look into gelatin-based resins for high resolution. Some of our collaborators have used this for studying tumor models, where they 3d printed this dome shaped structure over a spheroid of tumor cells to study the effect how the cells are are migrating. Also closely related to to the carous talk, you can indeed use this two photon polymerization to print micro blood vessels in. In this case this was a micro blood vessel printed lined with endothelial cells within a matrix of other cells and here it's to study the interaction and the diffusion of nutrients from the blood vessel to the tissue. So for these specific applications it can become very interesting to go into this high resolution. Another thing you can use it for is to study actually the influence of mechanical stimulation on cells. So here there's a cluster of cells printed inside, again with two photon polymerizations inside a device which can be activated using atomic force, microscopy to put forces on the cells and then see how the cells react to these forces. And then another model is again a tumor metastasis model. So you see, on top you see tumor cells and on the bottom you see a blood vessel compartment and you see here actually that the tumor cells are migrating towards the blood vessel to study metastasis in the human body, depending on the mechanical properties of the channels which are formed.
Speaker 3:Then, going to non-gelatin materials, polyester-based materials, this is again done with two-photon polarization collaboration with a research group of Professor Alexander Osyanikov from TUWIN, where they actually used this biodegradable polyester to make cages for spheroids. And why do they want to do that? Because if you have conventional spheroids and you put them together, they will stick together, they will merge, but then they will also become necrotic and they will shrink again, but by putting the spheroids inside a cage you can actually have them growing together without becoming necrotic and keeping up their volume. So in this case you generate an injectable high cell laden material which you can use, for example, for cartilage regeneration, and you can see here that actually this ferret takes up the shape of the cage. So you can even make something completely out of nature cubic spheroids or pyramidal spheroids.
Speaker 3:But in this case rand spheroids were needed and of course this is a very high resolution technology, meaning that, um, conventionally it was very slow to produce these things, but recently, uh, they developed a new type of two photon printer based on a resonance scanner, where they can actually upscale the production, because this is real-time printing, what you see here.
Speaker 3:They can upscale the production of these spheroid cages up to five to six thousand cages per hour, which is an incredible increase. It scans up to 5 to 6,000 kg per hour, which is an incredible increase. It scans up to 66 m per second, as you can see here in this live video. And then for extrusion, also using this Gelma material, which is very popular in collaboration with Glee Leuven uses for cartilage regeneration, so you can encapsulate cells in there. And what's interesting there is, you have a relatively soft matrix matrix, but you see over time that the cells are starting to deposit their own extracellular Matrix, thereby bringing up the um mechanical properties with a, with a uh, two orders of magnitude, showing the formation of actual cartilage. With that, I would like to thank you for your attention and if you have any questions, feel free to ask them.
Speaker 1:Thank you, jasper, fantastic presentation. We are running slowly out of time so I'd like to move on to our last speaker so that we have some time for discussion. But fantastic presentation. You do have some questions in the Q&A box, and thanks for submitting them, guys. So, jasper, you can actually type in the answer directly in the Q&A box. And thanks for submitting them, guys. So, jasper, you can actually type in the answer directly in the Q&A box for some of the questions, but we want to have enough time for a discussion at the end. So, if you don't mind, no, sounds good.
Speaker 1:Okay, I'm going to introduce our last speaker, scott Taylor, from PolyMed. Also, I want to mention that PolyMed is a sponsor for this event.
Speaker 6:Thank you very much for supporting us. Yes, thank you. I tell you this is a perfect webinar series to be a part of. Yeah, I think so many of the speakers already highlighted the importance of, you know, the biomaterial inputs to 3D printing and that's exactly. You know what we want to talk about today. So, and hopefully you know, looking at that in terms of these supportive materials for tissue engineering and overly tissue-based structures that we can print. So, yeah, that's the topic for today. I am the Chief Technology Officer at PolyMed and we will have a chance to talk about that.
Speaker 6:Let's see focuses on medical devices and specifically medical devices based on absorbable polymeric structures. So we synthesize materials Most often, these are more flexible or tougher, there's some unique nature to them and then we convert those materials into useful articles in relation to 3d printing. Uh, we'll, we'll hit on a couple of those, but, um, you know it's, it's filaments for uh, for FDM based printing, and then uh UV curable polymers as well. But but it's more than just that. We we make uh fibers and textiles. Uh, we, uh. We actually produced electrospun structures. Uh, I had the first uh medical device that was cleared by FDA that was electrospun a number of years ago that was developed and manufactured here and we continue to do that. So this is an example of some of the things that we've produced at PolyMed. So we are in South Carolina, so I know there's people here from around the world and it's kind of an honor. It's an honor to be presenting to you, but we've been around for a long time spent out of Clemson University about 30 years ago and the work that we've done has really been able to support a number of medical devices, both class two and class three implants, translating to millions of implantations but, I think, more importantly, advancing the importance and the technology of biomaterials synthetic biomaterials for medical devices. So, yeah, you know one of the examples here we do support FDM printing, so this is filament-based printing and our thesis going into this when we started this is about 2015 is when we jumped into the 3D printing application of these materials.
Speaker 6:You know, these additive manufacturing, like everyone else has said, has incredible potential to change lives and to change how we perform medicine. But there's a big separation between the technologies and the materials that were available at the time and how that they could be used to maximize their benefit, and that really is, you know, one of those aspects is mechanical competence, and we've talked about that. A number of the other speakers have talked about the. You know the mechanical potential of materials and the need to support, especially in tissue engineering, these newly developing cells and tissue-based structures through the early phases of wound healing, so that mechanical competence comes from a variety of materials and you need different performing materials depending on how you're using it. When I talk about mechanical competence it is you can think of it in terms of kilopascals of stiffness, so this would be in relation to a very flexible rubber or TPU-like material all the way up to the low gigapascal range, which would be on the order of hard tissues in the body. So bone and materials that we have developed here support that full range of performance.
Speaker 6:And then you know so, after we have this temporary support structure that we create, the intention is the materials will degrade over time and the tricky part about that is you know materials that need to be developed so that they're safe throughout that degradation time as well, so as they're degrading. Most of these degrade by hydrolysis, so we're generating byproducts throughout the degradation lifetime. Material need to be non-cytotoxic and all of these other components to support wound healing, especially for new cell deposition, but throughout the healing life and throughout the degradation life that we cannot elute any byproducts that would somehow inhibit the performance of the product. So here's an example of a filament-based feedstock that we have developed. We've actually supported five clinical trials with filament-based feedstocks that were produced at PolyMed and this is one example of a preclinical model that we put together around hard tissues and this feedstock was based on polyester but also combined with bioactive glass and beta-TCP to have that biologic cue that is really not available with a foam plastic polymer. So we were able to convert that into a high-quality, high-resolution device to fit very specific and complex geometries. And then we did perform a rabbit study with that to look at integration and health of the bone and you can see a CT scan from that. To look at integration and health of the bone and you can see a CT scan from that. So excellent infiltration into this matrix structure and great integration of these newly deposited bone to the surface of the implant. So we have high resolution. You can see the negative, basically, of the structure that was created.
Speaker 6:And then the best thing about the FDM-based feedstocks is these are thermoplastic materials. So these thermoplastics are very similar. They're not identical to materials that have been on the market in medical devices since the 1970s, so the regulatory pathway is very well understood. We know how to take a new version of a polymer and support that through biocompatibility studies, support that through all of the animal models, the GLP studies the in vitro degradation of both mechanical and mass over time, and provide a great story to FDA and support that. So it's really not a risk in developing a medical device to use a new polymer that's still based on historic technology. So very proud of these materials and I think it's a great starting point for biomaterials in additively manufactured medical devices.
Speaker 6:But we know this is not the end. Fdm does still suffer from lack of high resolution and there are definitely some limits in terms of what the material can do to create these highly resolved, especially small structures. And for that reason you know, over the past several years we have focused a lot on a new class of materials at Polymed that are cross-linkable and chain-extendable by UV curing. It's certainly not the only application in terms of DLP or SLA, but in terms of just a UV curable system that could be used as a thin coating. It can be used to create solid objects. I'm actually using this material in a photolithography application, making highly detailed cell wells, but in this case we've focused on the application to DLP-SLA and it's also been explored in two photons. So the material is compatible with a variety of techniques and through this we're able to create highly resolved cellular structures or even solid structures.
Speaker 6:And again, this material, we have focused on the higher flexibility structures, things like a foam or like a TPU-like material, but we also have the ability as a platform to turn that into a rigid material closer to that high megapascal or gigapascal range. The unique thing about light curable polymers based on polyester technology is that the photo initiator has to be at a certain level that supports biocompatibility, because it's a complete ink package, a viscosity modifier or a stabilizer or a filler or the photo initiator that is required to turn that into, you know, from that liquid material into a solid structure through the printing process and that allows the the biocompatibility, especially early in the degradation life and to be, you know, highly biocompatible, not not cytotoxic, etc. But then throughout the life. This material was designed as continuing to be researched in terms of safety of its degradation byproducts so they can be well characterized to support applications ultimately going to FDA or for EU MDR, et cetera. So, yeah, so, biomaterial throughout the degradation lifetime, very predictable, very compatible with sterilization techniques such as ethylene oxide or radiation sterilization, and it's been a big focus and we've come a long way.
Speaker 6:We actually have used materials in several preclinical models. At this point trying to just continue to build the volume of work so that it's easy to adopt either for academic research purposes or for targeted medical device development, and this is what we do. So we are a CDMO. The intent of the research zone at Polymed is to be able to apply those to medical devices. So we're very near in our R&D efforts. We're very near to the end goal of transfer of that into a marketable technology, and so that's exactly what both of these are for the FDM filaments as well as the SLA or DLP printable materials. And then we work with companies, we work with academic institutions to develop products and ultimately in the CDMO model we want to ultimately support that through manufacturing material supply of that marketed medical device. So with that, thank you guys, appreciate being here and I'd love to answer any questions about either materials.
Speaker 1:Awesome. Thank you so much, scott, great presentation. Okay, I'm going to invite everybody on screen, since we're definitely running out of time, but I want to be able to ask the panel a question and also we'll continue to have questions from the audience as we're going. You know, we've been hosting Biomaterium conferences for almost several five years probably at least every year and there's always complaint about the lack of materials to work with for bioprinting and medical device communities, and I think one of the reasons is just really slow to develop new materials. Biology is really really slow. My question is you know, in your line of works in the last years it sounds like everybody has been in this space for at least a decade. Are we accelerating the process of generating new materials? I'll start with you, Scott.
Speaker 6:Yeah, you know, I don't know if we're accelerating, but I think what we're starting to see I think Jasper presented some materials, ricardo presented some materials is that all of this work that has been going on for the past decade is now starting to come to light. So we're starting to actually see some of the fruits of this five to ten years of work. You know, I know, we were working on this photo set materials, what we call our UV curable system. You know, for six or seven years, before we even talked to anybody outside of our walls about it. So I do think that, and hopefully that does inspire, you know, additional research, at least uncover some of the challenges with the materials, so that we can continue to iterate upon that.
Speaker 1:But I think, yeah, right now we're just seeing the initial fruits of that last decade of evaluation.
Speaker 3:Great Jasper, yeah, so I think it all depends on what you consider new materials, I think so there is now, over the past well, 25 or 20 years, there have been some standard materials for example, gelatin or gelma is a very popular material and I think now we're at a time that they have proven their function, they have proven their compatibility. So now it's up to fine-tuning the properties by playing around with chemical functionalities or playing around with formulation to further fine-tune it. So I think it's not necessarily the era of new, new, new, new materials it's no longer there but it's more into fine-tuning existing materials to make them more performing, because why would you reinvent the wheel if it's already there? So that's a bit my perspective on it.
Speaker 1:Right, we're not new humans. We're still the same material.
Speaker 5:Exactly.
Speaker 1:Ricardo.
Speaker 5:I agree with the points made by Scott and Jasper, but I also wanted to add that there is also an increasing awareness as the technology has matured. There is an increasing awareness on the need for materials for specific applications, and that drives the development of targeted material for with certain properties, um, especially with the most much more mature technologies like extrusion, dlp that have been around for a bit longer, and and to photon as well, um, yeah, I think I think there is a clear drive in the research community and in the community in enabling new application, with variations of the materials, for example, and besides, of course, standardization, which is vital to go towards investing clinics, as Jasper also mentioned before.
Speaker 1:Yeah, totally Janina.
Speaker 4:Well, I agree with Dave. Yeah, totally, Janaina. Functionality and I think that the several materials that I can use in biofabrication can put some molecules or some modifications that help us better. So in my opinion, I think in the next years this field is increasing a lot. It's increasing more because of this type of researchers and companies that are looking for improving molecules, improving modifications, improving technology to get more biomaterials for humans and the other medicine field. I think, in my opinion, Great thanks.
Speaker 1:So I saw some of you guys presented generative design using computers and we have actually saw several presentations in the last year on various companies using machine learning, ai to characterize materials, for example. And then also there was an application from Singapore that we saw recently using AI, machine learning, to figure out the perfect cell density, composition of the material, to figure out the perfect formula, in a more accelerated fashion. So instead of like testing a thousand different formulations, for example in the lab, they can simulate in computer and have some kind of predictive algorithm. Any thoughts about that? I mean, we're really there yet, or this is still somewhat of a sci-fi.
Speaker 5:Maybe I can start with some thoughts. I think we are getting there. So things are becoming quite advanced and maturing very fast, especially when it comes to what you just said, jenny, which is improving printing resolution. So you can see, starting from the materials properties, without running many trial and errors, you can optimize. Starting from the materials properties, without running many trial and error, you can optimize your extrusion pressure or your light dose delivery. That will make, indeed, optimization of materials much faster and improve printing resolution. And it is already coming. So it's. There is, of course, some work to do still, but it is getting there. The work I used today we trying to do something a bit different, which is more of a co-design with the printer, that essentially the software of the printer thinks along with you to optimize the environment for the cells. That's a bit, of course, newer, but I see a future development in that direction as well.
Speaker 1:Great, excited to see more work out of your lab. Everyone else, please chime in. There's no need for me to just jump in. No need to be polite, okay, all right.
Speaker 3:I think well, since we are on the material aspect and not really on the design of things, but I think AI makes a lot of sense also there. You can input some feedback from your experiments and then try to optimize it. Uh, so much faster and more efficient than it used to be in the past in terms of, indeed, cell densities to use or um concentrations to use.
Speaker 3:I think over time you will basically be able to have like um on-demand properties that you. You would say I want a printed construct with just mechanical properties for this cell type and you would just get a recipe out of your AI technology. So I think it helps a lot with the optimization of certain things in the material composition.
Speaker 6:That could be, jenny, where you asked about the acceleration. I think that things in the material composition yeah, I think, right, that that could be uh. You know, jenny, where you asked about just the acceleration, you know, I think that the support system you know for doing that is now available. You know, we see um, you know things with uh, with identification of polymer properties and all of these things, uh, they're now available. You know, with the right data set, um and a generative ai platform. So you know, yes, using a set of materials, a subset of ingredients that we know is, is uh, is reasonable and safe and, you know, biocompatible, all these things, uh, we can now be much more targeted, um, as in terms of the properties, um, you, properties that we're able to achieve. So, yeah, it's a great kind of synergy between these technologies.
Speaker 1:Yeah, I look forward to it and actually I know there are instrumentations or instrument providers now are looking into the data set, their own data set and create applications to characterize materials and hopefully that would help the industry moving forward. The other final question I want to ask also is something that I think, scott, you mentioned in your presentation is electrospinning or melt type of 3D fabrication. Just kind of curious, you know, is everybody working on this side of the 3D printing?
Speaker 6:What are the challenges to develop material for this particular process in the realm, maybe not directly additively manufactured like we're talking about here, you know. But even if we look at, you know, a traditional product like a hernia mesh right, these are traditional knitted textile structures. You know, if they're degradable, they need to have an additional function of support and scaffolding, right. So electrospinning is another way to get at a structure that supports rapid integration and proliferation across the surface. So, yeah, we have a different set of materials, a different set of performance parameters that we look for with materials that support electrospun products, that we do for materials that are more suitable for additive manufacturing by filament, and even you know some of the powder-based technologies that are, yeah, that are available but underutilized, with absorbable absorbable plastics yeah, I think that is also another process, just like light-based 3d printing.
Speaker 1:there they can both produce very scalable products, and I think a lot of the presenters here really focus on probably the other, also very scalable process, which is the light-based products.
Speaker 6:It feels like scalability is important. Everyone wants to talk about that, everyone wants to talk about that. But I see a lot of similarities in the additive manufacture that we saw 20 years ago with electrospinning A lot of promise, but no one thinks it's that scalable. But for the application it works great. It's highly controlled surfaces with electrospinning, a lot of academic research, followed by some smart applications that are now translating into really scalable products. So hopefully we see that same trend with these additively manufactured materials and products.
Speaker 1:Absolutely Okay. I'm going to conclude this webinar by asking everybody to just say one thing they really wish to have right now. Because you know, these speakers are donating their time for free. I got to give them something back. So, to pay back for this webinar, I'd like you guys to just shout out what you want right now. I'm starting with Ricardo. I think he already said he wanted a graduate student or postdoc.
Speaker 4:You can say one more wish.
Speaker 1:Yeah, you can say one more wish.
Speaker 5:Yeah, so besides new team members, I would say easier access to as much raw material as possible. Okay, so we can do research with it, but I think I know For free, for free, yeah, maybe Some of the companies here want to team up.
Speaker 1:Okay, sounds good, janela. What about you? What do you wish for right now?
Speaker 4:Well, there are many problems in this field, but we cannot stop and I am here to improve more and more this area with you and the disease.
Speaker 1:Great, awesome, scott. What do you want right now?
Speaker 6:Yeah, the volumetric printers looked very interesting. I'll take one of those. We'll share some materials. We'll get a volumetric printers looked very interesting. I'll take one of those. We'll share some materials. We'll get a volumetric printer and maybe a sandwich, I don't know. It's lunchtime.
Speaker 1:That's what I was going to say. Everybody wants some food. Yeah, absolutely, coffee or food either, jasper, what about you?
Speaker 3:Well, I would say, some more customers. So if you want to accelerate your research and don't have to start from scratch, get your materials with us and it greatly advances where you need to go. I mean, we're already doing that with Ricardo, we're already supplying him with some materials and there's more where that came from.
Speaker 1:But not for free. That is the key.
Speaker 3:That's something we will discuss in the next two weeks, I guess.
Speaker 1:Okay, awesome well, that's a really nice conclusion that we have. Thank you very much for joining us. This will be on demand for free for a couple weeks, so invite your students colleagues to watch it so they can learn as well as I did. Alright, okay, until next time. Thank you everyone, goodbye, thanks thanks, jenny.
