Orthopedics Meets 3D Printing: A Journey Into the Future

We examine the pivotal role of 3D printing technology in reshaping orthopedic implants and enhancing patient outcomes in this virtual event. This discussion navigates the crossroads of innovation and caregiving in modern medicine by featuring expert insights from industry leaders. 

• Focus on patient-specific implants and their clinical implications 
• Discussion on biocompatible materials and new technologies 
• Regulatory landscape for 3D-printed orthopedic devices 
• Insights on surgical practices and patient recovery trends 
• The benefits of personalization in surgical interventions 
• Investigations into osseointegration and design efficacy 
• Evolving market dynamics and future trends in 3D printing 

Listen to this virtual event recording, a thought-provoking exploration of 3D printing's revolution in healthcare and the impact of innovation in the orthopedic space!

Full on-demand recording: https://3dheals.com/courses/3d-printed-devices-in-orthopedics/

Chapters

• 0:00 Introduction and Event Overview
• 15:20 Jenny Chen on 3D Heels and Its Mission
• 37:10 Insights on Networking in the 3D Printing Space
• 54:00 Trends in 3D Printing for Orthopedic Devices
• 1:16:30 Garen Njakian on Bioceramic Post
• 1:35:50 Nathan Evans Discusses Patient
• 1:50:40 Kuntai Akhtas on Innovations in Additive Manufacturing
• 2:10:15 Kyle Kovach Explains Regulatory Challenges
• 2:30:00 Q&A Session and Audience Engagement

Transcript

Speaker 1: 0:00

And, okay, let's just make sure everything works. Okay, I think people are trickling in. That's great. Hello, hello, hello, good morning, and some of you guys are mid-morning now. My name is Jenny Chen, a founder and CEO of 3D Heels. I just want to say a couple of things about 3D Heels before we move on to this incredible panel and incredible topic 3D printed orthopedic for orthopedic devices.

Speaker 1: 0:32

I started this almost eight years ago seven or eight years ago, I can't even count because you know it's more than a handful and my our mission. There are three missions. One is to educate people about 3D printing and what it can do for healthcare, and I think over time it evolves into this kind of virtual event. It's not just educational, but also conversational. We want to talk to each other and we can't afford the plane ticket anymore. It's getting more and more expensive. Traveling in general is logistically complicated, so we want to bring people together. We can have this kind of conversation, educating each other, and also engage our audience, because I know we have a lot of smart people in the audience who want to have a conversation and love to engage you guys, and this is the kind of conversation we want to have. And number two is networking. So in the chat box, feel free to put your LinkedIn link, your social media link, and you can directly message any speakers you have questions. And if you have questions during the event, feel free to put them in QA box. Our moderator Craig today, so he can manage I can also help, but still, put it in a QA box is more organized. So networking is number two. We are actually having an in-person event in a couple of weeks in San Francisco, so if you're in town on March 27th in the evening, please join us.

Speaker 1: 1:58

And number three is we have a program called Pitch3D. I'm really proud of this program because since 2018, we have hosted more than 70 startups and I've seen literally some of the startups has grown from, you know, one employee to 30 and some are raising round B and C now. So really proud of this group. So Pitch3D is a program is a free program for early stage startup, so pre-seed seed to series A in healthcare, 3d printing and 3D technology. So AR, vr or any kind of CAD program, cad software, design and any SaaS related to additive manufacturing in healthcare. They're all included. We're not really restrictive to just 3D printed or 3D printing the machine, that kind of thing. So we're actually pretty, pretty wide space. So that's number three.

Speaker 1: 2:55

So I want to introduce our moderator today because he really is a moderator extraordinaire. I know Craig for more than five years now, is that right? During the pandemic we met each other. Virtually. Only last year we actually met each other in person and he's also the community manager for New York and he's doing a fantastic job. And he's also the president of HyMet and so I'm really happy we have him as moderator. He's probably a better moderator than me. He's extraordinary.

Speaker 1: 3:29

But before we move on to the panel which Craig will introduce us to, I just have a couple of slides I want to share with people, because I'm always kind of curious is where is 3D printing in healthcare? Because the numbers put out by analysts I'm not 100% confident about those numbers because I know there's some numbers throwing out saying the total market for 3D printing is about $20 to $30 billion and I'm always curious like, well, okay, is that number accurate? And where is healthcare? And, more importantly, I have to say I I see orthopedic space is growing a lot more than many other spaces we focus on. That includes bioprinting and prosthetics, you know stuff, and dental. But where does this panel stand? Um? So I want to share just a couple of slides and let me see where did my hold on one second? My PowerPoint presentation was working. Hold on one sec. Okay, here we go. There you go, okay, all right. So a quick market analysis from my own research.

Speaker 1: 5:03

I have reviewed, basically the public company, some of the largest public company companies, public reports, so their SEC filing the most recent ones, and let me just collapse my thing here and I have noticed some really interesting trends, since I am not an orthopedic surgeon and when I was training in medical school we did not have any robots. That should kind of date me how old I am now. But now almost every large orthopedic implant companies have robots and they also have 3D printing and they combine these two technologies together to increase efficiency, accuracy and improve clinical outcome. So that's a really interesting trend for me. I think some of the benefits of 3D printing for orthopedic implants are clearly known to this audience. So I don't want to take that away from the speakers as well, because they're more expert than me in this. But here's a quick comparison on where is every the larger companies are going, and we certainly have some rising startup like Restore3D in the speaker panel, who Nathan is going to tell us more about where the cutting front frontier is. But these are the big players in the space and, as you can see, everybody has a robotic system that works with a 3D printed implant and the implant also has the engineered surface geometries to make these operations safer and the outcome better. Make these operations safer and the outcome better, which means the implant lasts in the patient, maybe even beyond the stated 10 to 15 years and less complication.

Speaker 1: 6:57

Okay, and so the other thing interesting is we're also talking about fully customized, customized, semi-customized versus fully customized implants, and the companies who are manufacturing what we always think 3D printing for is the patient-specific implants where, you know, every implant is designed for every single individuals and every implant is different because, you know, we think we can have complexity for free. So, uh, it makes sense that everyone has their own implant, but actually the reality is only a minority of the 3d printed implants are completely patient specific and you see some of the companies who does this here and the you know. Restore 3d is one of them, which we will hear more from nathan soon. Um, and then I think the majority, the millions of implants we have, that's 3d printed year annually, are actually from our semi um, adapted, so they're adapted 3d printed implants. So so they come in different sizes or they can be modified to fit a particular patient. They're not really patient-specific, they're customizable. So that's another interesting finding.

Speaker 1: 8:15

And then come down to the money part, and these are just estimates. So nobody actually specifically come out because you know the orthopedic implant industry, they did not come out to grow the 3D printing industry. That is not how it goes, the implant manufacturer, they just want to make better products and generate revenue. So this is only an estimate. Nobody in our report says, ok, our 3D printing you know CapEx is generating this kind of ROI. There's nobody saying that and sometimes you can't even find those numbers. So these are just estimates.

Speaker 1: 8:50

And, as you can see, for most of the larger players the percentage of implants as 3D printed is about 15 to about 15% and J&J, even though we know it as a leader in this space, percentage-wise, it's also got a bigger denominator in terms of total revenue. Percentage-wise it's actually relatively less, but if you add the numbers of the total estimated 3D printing revenue it's about $4 billion. And so if you believe the low range number of $20 billion total market and you know $4 billion revenue. This is annual revenue. You can see that how significant healthcare is. I mean, just orthopedic implant alone is part of healthcare. 3d printing. So again, I don't think the 20 to $30 billion market size it depends on how they calculate it is extremely accurate. I also think that this speaks volume of how important it is. 3d printed orthopedic implants, or just implants in general, is in 3D printing. Okay, so that's all I want to say.

Speaker 2: 10:15

Thank you, jenny. That was an interesting set of data to begin the conversation, and thank you for the kind words as well. You know, let's all acknowledge the hard work that Jenny does in putting together great events like this, and the timing of this event was really appropriate, given that the American Academy for Orthopedic Surgery conference is coming up in San Diego March 10th through 14th. Many of our speakers will be in attendance and we thought it'd be a good opportunity to establish conversations, virtually so for those of us that are going to be in attendance, great opportunity to meet and continue the conversation. So again, without further ado, good morning, good afternoon. We have people from all over the world, so it's always great to have these events.

Speaker 2: 10:59

My name is Craig Rosenblum. I'm the president of HyMed. We have a great list of speakers lined up today and really the goal of this presentation is to understand 3D printing and specific applications that are up and coming in orthopedics. If this was a webinar, say, five, 10 years ago, I think there would probably be some skepticism as far as the practical application for 3D printing in orthopedics. But now, as the data that Jenny has shown you know, really things are up and coming and there's so many companies especially I'm looking at Nathan companies that depend on 3D printing and many companies in the orthopedic field that probably would not be in existence if 3D printing was not a thing.

Speaker 2: 11:46

So, without further ado, I'd like to introduce our first speaker, my colleague and friend, garen Njakian. Garen is sitting literally right across the room, right across the hall here at Hymed. Garen is our engineering manager at Hymed. So Hymed has been in business for over 30 years as a global leader in calcium phosphate. We manufacture calcium phosphate materials for plasma spray coatings and surface treatments, and were in existence long before 3D printing was a thing. Garin and his team collaborate directly with dental and medical device manufacturers around the world to provide innovative biomaterial solutions. Drawing on his experience with all three major classes of medical devices, garen's work in the medical device industry over nearly a decade has centered on process optimization, root cause analysis, mechanical design and quality management systems. He holds a bachelor's degree in biomedical engineering, with a minor in robotics from Johns Hopkins University and a master's degree in biomedical engineering from Duke University. So, garen, the floor is yours.

Speaker 3: 12:59

Thank you very much, craig, and good morning, good afternoon, to those in different time zones as well, so I will share my desktop here and hopefully all can see these slides, all right, so thank you again for all being here. I'm going to touch on specifically 3D-printed devices in orthopedics, more specifically bioceramic post-processing, and, as Craig mentioned, my name is Garen and happy to be here and hear your thoughts on the talks today. So, in brief, himed, what do we do? What is our company all about? Right, so we've been supporting the orthopedics industry for over 30 years, supporting 3D printing for as long as 3D printing and orthopedics has been around, so let's say the last five to 10 years. And we have three kind of main focuses in our organization. We are, first and foremost, a biomaterials manufacturer, so we create different calcium phosphate forms that get used into bone grafts, bone putties, bone void fillers, things like that. But then we also take those materials and create biocompatible surfaces with those. So things like plasma sprayed hydroxyapatite or things like resorbable blast media texturing to increase the surface area of dental and orthopedic implants. So we do things like contract manufacturing for different companies as well as purely R&D work for a number of up and coming and larger, established organizations. We have things like SEM, xrd, along with other capital equipment that we use on a daily basis, not only for our customers but also for our own internal engineering and R&D work. So to kind of set the stage of moving over to additive, something like Matrix, ti or titanium plasma spray coating is something that Hymed has done for well over a decade now and that still is a market for that. But we are seeing this shift in the industry of creating your porosity and your controlled porosity through additive manufacturing. So you get the porosity that you want built into the CAD and built into the print itself. It removes steps from the supply chain and you can scale it, as you can see from this image from Anthropologie. So we've seen that as an industry trend as well.

Speaker 3: 15:16

Moving over to additive, talking about 3D printed titanium, I'm sure others on this call are more well-versed than I am, but my understanding is that there's basically two paths that most companies go in terms of powder bed fusion technology for titanium 3D printing. The first is scanning, laser melting, or SLM, and the second is E-beam or electron beam melting, ebm, and what we can see here is that the starting powder size is much smaller for SLM than it is for EBM, depending on the printer and your settings and things like that. But generally speaking, and what we see on the untreated surface after printing is you have these partially molten or residual beads left on the surface. A takeaway that we found in our research is that the size of your feedstock or your powder bed to start it actually drives the size of the residual beads at the end. So if you're using an SLM technology, you can see on the scale bar you're going to see smaller beading and then if you use the e-beam technology, you'll see larger beading on the exterior of your parts. When we look at some final parts that we've had in-house here at Hymed, when we look at some final parts that we've had in-house here at HiMed, we've had parts that are sent to us for other areas of processing and in the 3D printed area they were not post-processed at all, even though they were meant to be final devices.

Speaker 3: 16:35

Moving on to the field. So, interesting enough, if you see the top image there where I put an arrow, that bead I was trying to take a second picture on our SEM and by the time that second picture was snapped that bead was gone. So it really gives an idea of how loosely adhered or cracking, as you can see in the bottom image some of these beads really are. They're not partially melted or fully adhered. In some cases they are barely hanging on. And other customers have sent us parts as references for us to work with for us to post-process other parts. But the parts they sent that they said were completely processed, we saw that there was still significant beading on the parts. So I think this really shows that a lot of manufacturers either don't fully post process or don't post process their parts at all to remove those residual beads that remain on the ends of prints residual beads that remain on the ends of prints.

Speaker 3: 17:28

This is a little bit of work out in University of College London and others on three commercially available acetabular cups. If I said the company names you'd know them. You can read the paper. But this was using SLM and E-beam depending on the part. And again we can see that those commercially available cups had partially molten loosely adherent beads or even clusters of had partially molten loosely adherent beads or even clusters of multiple beads and loosely adherent beads together in the sample C there. So I think now that we've established that the beads exist after printing and some folks kind of don't recognize that yet that they exist or that they might need to be post-processed.

Speaker 3: 18:02

We wanted to do a little bit of research on what are the stated concerns in industry with the residual beads. So rather than take my word for it, I ended up pulling a couple of sources from publications here. So the first one is one concern is that particles falling off from the surface as wear debris may cause aseptic loosening of the bony prosthesis. We know that aseptic loosening is one of the largest failure modes for these types of implants, so that is a concern. The second is that the clinical impact of these partially molten beads needs to be understood, particularly if this may increase the release of titanium for the implants. So this is something where maybe tabor abrasion or other testing can be performed to see the level of beads that would be removed when being placed in vivo. And then the third, which we'll touch on more in the coming slides, is in the course of analysis of specimens cracking surface in stress tests or strength tests. Rather, they have observed voids and unmelted powder, and the crack initiation locations occurred in the form of unmelted or partially melted metal powder particles. So these are areas where there may be different stress concentrations because of the non-uniformity of those last layers of your print which could become crack initiation sites.

Speaker 3: 19:13

And now that we've talked about some of the concerns, what are some benefits to post-processing and what research and experiences Hymet had out there to see what the benefits could be? So this was a study done in a rat model or multiple rat model, where they 3D printed implants using SLM and then they either left them untreated so that's A and B on the pictures there or used an acid etch to remove the residual beads, so that's what we're calling 3DA and that's images C and D. And they implanted these into animal models and performed histological analyses at three and six weeks and they found that the treated samples had an increased bone implant contact that was statistically significant at both three and six weeks and had bone MSC proliferation and osteogenic differentiation that was higher than compared to the as printed part. The next is a little bit of more research that we found in our literature view as well as some customer data we have on file. So the top is from a paper and those SEM images are from a paper as well, where the post surface treatment imparts a compressive residual stress on the surface, increasing fatigue life by slowing down the initiation of cracking. So what they found was that using a bead blasting technique, they could smooth out this surface, get rid of some or get rid of those residual beads and any initial crack initiation sites that may have been forming and impart some compressive stress and increase their fatigue life processing. And normally they'll send us parts that were printed and then they did hip or hot isostatic pressing on the parts or they sent us those samples that went through those two actions and we blasted them afterwards and they found that the parts that weren't blasted by Hymed, there was large variability in number of cycles and fatigue strength as compared to the Hymed parts and that the Hymed parts were 50% increase in fatigue life across the board. So we've seen this across multiple customers and we've convinced ourselves there's value here based on our customer data.

Speaker 3: 21:14

Next I want to talk through just a few case studies again of some work that we've done here at HyMED. So this is an image of node post-processing. I don't need to beat the dead horse on the beads existing. They were there and we ended up taking some of these 3D printed lattices and aluminum oxide blasting it. That's a common grit blast media that's used and when we did blast we see that it does effectively remove those residual beads. However, we see embedded contaminant remains on the implant surface. So all those darker areas there, the dark gray that's aluminum oxide still embedded in the surface of the part itself. But using something like Matrix MCD, our proprietary apatitic calcium phosphate abrasive, you end up having a biocompatible post-processing producing a clean and contaminant-free surface following passivation. So you get your microtexturing and things like that and you get rid of those residual beads, but you don't have any embedded particles and no aluminum oxide, obviously, in your process.

Speaker 3: 22:13

The next this was just a little bit of fun we had in Python a couple of months back.

Speaker 3: 22:17

So customer had sent us some parts that we treated and they had sent us a few parts that were aluminum oxide treated in terms of the blasting, and we wanted to figure out how do you quantify what percentage of your surface is no longer your osteoconductive titanium alloy, what percentage of your part is now covered in aluminum oxide?

Speaker 3: 22:36

And so we did some histogram based and adaptive thresholding and then you can plot out the pixel intensities based on the images themselves to say how much dark spots am I seeing on the aluminum oxide as compared to the matrix MCD treated surface where you then passivate and remove the calcium phosphate, leaving the pure titanium alloy. So I think this next slide shows it a little bit better where. Up to 10% of the surface, it depends on where you put your thresholding. But you can kind of see on the right with the red graph of the aluminum oxide blasted part, you almost had a bimodal distribution where you have a larger cluster in that lower pixel intensity and that's all, the aluminum oxide being the dark spots in your image. As compared to over on the right side, that's your titanium alloy. As compared to the blue with the MCD you have a single crisp peak and that is your MCD-treated titanium alloy. That you have left over. So it depends on where you put your thresholding.

Speaker 3: 23:31

But anywhere from 5% to 10% of the surface, at least in the samples we've seen in-house here at Hymed, is really aluminum oxide. It would be glass beads. It would be other materials that are not able to be dissolved afterwards, such as something like Matrix MCD. So that's all I have to share today. Obviously, you know this is just learning a little bit more about our experience here at Hymed with this topic, as well as some literature research, but very excited to hear what everyone else in this room and the other panelists have to say on this topic, so that we can all learn and grow the industry together. So with that I will stop sharing and thank you very much.

Speaker 2: 24:09

Thank you very much, karen. That was very interesting, but I might be biased, because we work for the same company. I see that there's quite a few chat in the conversation in the chat room and, just looking through names, there's a lot of familiar faces or familiar names, and I know the faces that go with the name. So it's nice to see so many people that have joined. Um, I think we're going to do q a at the very end of the meeting. So, with that being said, we appreciate garen for sharing, and next I'd like to introduce our next speaker, nathan. So, nathan, why don't you share your screen?

Speaker 4: 24:49

let me get myself off here.

Speaker 2: 24:54

So, for a shameless plug, both Hymed and Restore3D will be exhibiting in adjacent booths at AAOS next month. It just so happened to work out that way. So if you're interested in what Garen had to share and interested in what Nathan is about to share and would like to continue those conversations, then please look for us at AAOS. Restore 3D is exhibiting at booth number 3439 and HiMed directly adjacent at booth number 3546. All right. So, nathan, your screen is up, but let me first introduce you properly.

Speaker 4: 25:32

Is it up correctly?

Speaker 2: 25:33

Yes, it is up correctly. Thank you, it is up. But let me first introduce you properly. Is it up correctly? Yes, it is up correctly. Thank you, it is up correctly. What happened behind the scenes? No one has to know. So Dr Nathan Evans leads product development for Restore3D. He joined the company in 2018 and has been a part of clearing and launching numerous additively manufactured products in the orthopedic space. Restore3d's focus is on personalized surgery realized using 3D printing. Prior to Restore3D, Nathan spent two years at McKinsley Company as a consultant to large F500 companies. He obtained his PhD in material science and engineering at Georgia Tech. He currently lives in Durham, North Carolina, where Restore3D is headquartered. Nathan, the floor is yours.

Speaker 4: 26:20

Great, thank you for that introduction. And yeah, as he mentioned, I lead product development at Restore3D, a company that utilizes additive as well as some other enabling technologies to deliver personalized implants, and so what I'm going to do here is really focus on the why of utilizing additive for orthopedics and then touch briefly on some kind of case examples and some where I think maybe the industry is going a little bit, but save a lot of that discussion, I think, maybe for Q&A. So again, this kind of a three-part talk where I'm going to mainly focus on part one here why use additive in orthopedic design. So first I want to present to you this patient which we would say previously had no option. This is a severe trauma case with a large defect in the distal tibia. So it might be hard to understand what's going on for those not used to looking at images like this, but this is an ankle of a patient and I believe it might have been a motor vehicle accident, but severe trauma like this. Maybe a surgeon could use traditional plates and screws to try to reconstruct this, but this would be a very, very difficult surgery without the use of, maybe, a patient-specific implant.

Speaker 4: 27:27

A second case same region of the body but a very different indication here. So this patient is a cancer patient. So there's an osteosarcoma again in the distal tibia. To be able to treat this they needed to resect a very, very large portion of this bone and again, without the introduction of additive patient-specific implants, this patient would have also historically had no option and maybe would have been facing a below-the, below the knee amputation. So these two cases kind of highlight often what people think about at least with our company of why use additive, and that's for patient-specific devices. But these really really kind of one-off, unique, very, very complex spaces. But I want to show why that this is not just for the one-off complex but it's for your everyday. And so one of the things I just did was did a PubMed search on the use of patient-specific implants in the literature. You can see there's just been an explosion of activity over the last 20 to 30 years and this is not just in the basic science. This is translating into commercial activities. With a study put out by the FDA they show how many clearances they've received that have been on additives. So this was in a Nature Review of Bioengineering publication that the FDA did and it shows the number of devices cleared over again. The last kind of call 15 years here, I guess at this time of publication is about 10 years and again really showing that this has been exponential growth.

Speaker 4: 28:51

But I think what's important to maybe point out here is we often think about the use of additive being implant focused, but a lot of the clearances you'll see here are not necessarily implants. You have them on things like software, cutting guides, things that make up a decent percentage of these clearances that maybe go underappreciated. It's some of the enabling technology. Again, cutting guides are critical to if you're going to use a patient-specific implant, you need a way to make sure that you're appropriately prepping the surrounding bone and you need a patient-specific cutting guide to do so. And then software this is things like the ability to take a CT scan and create a segment that and create a three-dimensional reconstruction of the patient's anatomy or some of the other digital workflows that are used to create patient-specific devices. There's a lot out there in the software side, particularly as we start to think about automating some of these activities as well.

Speaker 4: 29:42

So I want to again make the kind of point, though, that it's not just for complex cases. What about kind of the more everyday case and so an everyday case that often you know many of us are familiar with is a total knee surgery or total knee replacement. Many of us know a family member or an acquaintance who've had a total knee, and this just with dwarfism on the left versus an NBA player on the right. These are actually two cases that we as a company have done and these are not to scale on the screen but are to scale relative to each other and again shows you the size disparity that's out there with different patients. But you might kind of make the argument that these are still outlier patients. You said we want to make the argument that it's not just for kind of complex, one-off cases and these are still fringe cases, and you're absolutely right.

Speaker 4: 30:40

So what I want to do is kind of walk you through a little bit of the way we think about knee anatomy and then some interesting data that'll show you why it's important to have patient-specific implants for kind of quote, unquote your everyday patient. So these are two different, real, real patients a right knee and a left knee, and the patient on the left we would call bow legged and the patient on the right we would call knock knee, and the way we define, that is by these angles. So the LDFA, that's a lateral distal femoral angle, and then the ML, that's just your, your medial lateral width there. But on the patient on the left that angle is less than 90. And the patient on the right, that is greater than 90. So now that we've defined that, I want to show those two variables on a scatter plot. So this is a scatter plot of 85,000 different patients.

Speaker 4: 31:29

Sorry, I got to move my little bar here on Zoom so I can see my full screen. But what we did, we plotted these 85,000 CT scans this is in our database from patients that we've treated over time and we plotted those two variables. So just looking at the femoral medial lateral width and again the AP depth, and then we'll look at the angle in a second, you can see this wide, wide range of patient anatomy and then you can also see how there's a little bit of a bifurcation around our male and female anatomy. But then what we did is we actually plotted these two variables. We looked at sorry, it's not advancing here we plotted the offering of some of the largest competitors on the market, so JJ, stryker, zimmer, biomet, smith, nephew and Medacta, and what they're doing is trying their best to kind of match the standard scatterplot of the you know general patient population.

Speaker 4: 32:22

But you can see this leaves a lot to be desired. There's a lot of patients that aren't falling right on this kind of linear curve. And what do you do with them? Well, the surgeons just pick the best option they have and to you know, to be fair, the outcomes are pretty good. Patients are generally happy with knee surgeries as well as other procedures like hip replacement et cetera. But there's also data that says there's a high percent of patient dissatisfaction and pain, as high as one in five or about 20%. And while that might sound like it's pretty successful, you know 20%, you know essentially failure rate for a procedure like this is leaves a lot of room for growth here.

Speaker 4: 32:59

So again let's look at that other variable, that lateral distal femoral angle plotted against the femoral ML, and again plotting the other company's implants on the, and here you can see the spread is a little wider. Most companies only offer a single angle. They provide it in 90. Because again, you people, less than 90, greater than 90. So they just say let's just offer it in a kind of one size fit all and they just simply come in different widths. There's only one other company that is offering an angle at 87 degrees there, I believe.

Speaker 4: 33:25

So I want to show you, though, some data that says personalized implants do result in better clinical outcomes. So there's a lot of studies here. These are studies published all over. Some of them we've collaborated on, others are from other companies that say that these types of implants, when you have some personalization to them, result in better fit, better alignment and then, importantly, the outcomes are better better range of motion, better function, higher patient satisfaction and then overall better health economics. Why is that? Because there's less chance for having a revision surgery, less shoulder rehab, quicker return to work, etc. So this is well studied in the literature.

Speaker 4: 34:01

And then our specific implant, the Restore3D patient specific knee, has the lowest revision rate in the UK database, the UK registry, at only about 1% at 10-year follow-up. So this is about half of compared to kind of standard off-the-shelf implants. So we know that the use of additive can allow for these again one-off, complex trauma cases, oncology cases. That I think is fairly intuitive and obvious. And then it's also obvious to say maybe these outlier patients again, the NBA player or the patient with dwarfism, maybe that is an intuitive, obvious case for where patient specific matters. But I want to make the case again that even if you fall within the general bell curve there, um, you still have a lot of of opportunity to have a better outcome with with a patient specific implant that is made uniquely for you, and so that, to me, is is, again, one of the big advantages of additive is is it?

Speaker 4: 34:59

What was once an idea, personalized medicine is now a reality, and this is not just again in that kind of academic space, it's actually getting kind of mainstream press now. So there was recently a wall street journal article as recent as that this was published in August that talked about how there's younger and younger patients getting total knee replacements down into the 40s, which it would have been unheard of a decade or two ago, and they talked about what is enabling this. They mentioned robotic surgery, which Jenny highlighted earlier, as well as custom fitted 3D printed prosthetics, which, again, are getting such better outcomes that you don't have to worry about the need for a revision in 10 or 15 years like you used to. These implants are lasting much longer, patients are doing much better and, again, the big companies are highlighting this. Jenny mentioned earlier some of the trends she's seen and some of the data that suggests what percentage of their sales is due to additive manufacturing. But I'll kind of highlight on some of these quotes here. Stryker is talking about how they are excited and are growing their capabilities in the area of individualized implants. Zimmer talks about how they are making an increased effort into getting into true personalization for each patient, and then Smith and Nephew talks about how their total hip system is moving forward with a personalized mechanism as well. So kind of you know it's not just small startups doing this, everyone is seeing the benefit. So that's one of the huge pillars in my mind of why use additive is patient specificity.

Speaker 4: 36:27

I think Jenny in her intro slide had another one which is improved osteointegration, and Garen touched on this a little bit as well with some of his studies, and that is to introduce porosity for improved bone ingrowth into implants. Here's just a histology cross-section of an implant or of a study that we did with a porous implant versus solid implant. Pretty obvious Obviously solid doesn't have room for ingrowth. So it may be a boring picture there, but I think it highlights the case here that not the only reason for additive isn't patient specificity. In fact from that same FDA study that I highlighted earlier. They actually make the point that 73% of devices that are additively manufactured are not patient specific. And why do that then? It is for for porosity, mainly um, and the the improved osteointegration and bone ingrowth that you get from that.

Speaker 4: 37:18

So there's been a history of this for a long time. I'll just throw all this on the on the screen. This really kind of started in about the 1980s with centered beads, uh, where they were trying to find ways to get these metal implants to to better integrate with the, with the bone um, here you really more of a surface osseointegration though, because this wasn't bulk porosity and it was also very challenging manufacturing, costly, et cetera. Then in the early 2000s you started getting porous foam. This is some pictures of some Zimmer trabecular metal. Again you got improved osseointegration, because this is more of a bulk porosity now, but you still have more challenging manufacturing. You can't just like easily create any shape and again the cogs are a little higher than you'd like to be, particularly compared to subtractive means. But, starting about a decade ago, we started to see 3D printing become more mainstream for implants and started to get the first clearances through the FDA and the first use of these in commercial applications, and you know you have more seamless manufacturing care you get. You can mix and match where you put porosity, so you can dial it into regions that are critical. You can tune your properties, not only with regards to osteointegration but things like strength and fatigue performance, and so now we've seen the widespread, and this is this is hope fairly basic and well understood at this point.

Speaker 4: 38:36

But I but I think it's worth revisiting. Um, smooth implants simply don't osseone great, and but the thing is there's been a perception of certain materials of of being poor and others being more gold standard for bone and growth. But I'd like to make the argument here that so much of it is due to the surface geometry, or even the bulk geometry, and not the inherent material itself. So one example that is often highlighted is smooth peak versus titanium coated peak. Smooth peak has very, very low shear strength in a bone pushout model, and then titanium coated peak has obviously an order of magnitude better there, and so the conclusion might be titanium is way better for osteointegration than peak. But that's not necessarily the case, because if you look at porous titanium here you can see that when you add porosity you get another order of magnitude. Jump and smooth titanium is actually quite poor as well. So when you polish titanium, it performs basically the same as peak, and so what the conclusion here is is, again, it's not necessarily material, although material does have an impact. There are certain materials that are going to elicit, maybe, a fibrous tissue response and lead to more poor integration, but structure dominates the response compared to the inherent material itself. So where are we at today?

Speaker 4: 39:54

Today, spine is clearly the market leader in 3D printed implants. It is ubiquitous in this industry. If you walk the floor at something like Academy or at NASS, which is a large spine meeting, you will see it's not an exaggeration to see probably hundreds of company of spine companies that offer a 3D printed implant, and the reason why is they were the one of the first kind of spaces to realize again that porosity matters so much, particularly in a fusion application and in spine. What we're often looking for we're looking at is fusion. Lower extremity, though, is not far behind, so in kind of total ankle and bone wedges for things like osteotomies, you see a lot of companies utilizing additive now as well, and then upper extremity is slowly getting into this, like Zimmer and Stryker have made some efforts into personalized implants and something like a total shoulder replacement, but it's still pretty early. And then things like trauma are far behind, even though that might be an area where you could have the most efficacy again with these patients that just have large defects and no other you know solution. There's just not much out there for them today. And so I think there's so much room for growth.

Speaker 4: 40:59

Even though we think that 3D printing and, you know, the additive solutions have really penetrated orthopedics, it hasn't. In some spaces, like spine, yes, it's kind of commonplace, but in others there's a lot of opportunities still. So I'm going to just maybe show you just there's a lot of opportunities still. So I'm going to just maybe show you just there's a lot more here and we don't have time to go through it all, so I'm just going to kind of throw up one more screen here that'll just kind of show you I'll click through these the diversity of implants that we do at Restore3D. That might be a little bit of inspiration and lead to maybe some good discussion at the end, to just show you how this technology additive manufacturing and orthopedics can be just applied across the entire body. So as I click here, you can kind of just see the range of implants that we have done as a company.

Speaker 4: 41:39

These are all restore 3D devices where surgeons bring to us complex or unique clinical cases and we partner with them utilizing additive as well as some other digital design tools to be able to treat these patients. So again, this technology has a utility across the entire body and it's really exciting to kind of see where it's gone in the last 10 years. But there's a lot of work ahead and I think we can continue to offer these solutions to improve surgeons' ability to treat these cases, but as well as improve patient outcomes. I'm excited to see where the industry takes us. So with that, I think I'll pause Again. I don't want to run over time and we can save any additional discussions for later, but thank you for the opportunity to present.

Speaker 2: 42:25

Nathan, really, really interesting. I'm glad that we're going to be together at AOS. I just wrote down about five questions. Maybe we'll have time at the end. I thought the timeline that you shared was really interesting and certainly impressing upon the audience. The importance for porous surfaces is quite apparent, so excellent job.

Speaker 2: 42:46

Next up is going to be Kuntay. So Kuntay comes to us in Turkey, so why don't you start to share your screen? I'm saying, yeah, Perfect, it works Real quick. Before you start, for those of you that have just joined, welcome Again.

Speaker 2: 43:05

This is a presentation clearly dedicated to 3D printing and orthopedics. We would encourage you to submit any questions that you have for the panelists through the Q&A portion. We'd be happy to address your questions and have panel discussion at the very end of the conversation. Without further ado, please let me allow time to introduce Kuntai Akhtas. So Kuntai is a passionate entrepreneur, technology executive and strategist with expertise in additive manufacturing, medical 3D printing and additive manufacturing technology applications, With a background in mechanical engineering and a master's degree in bioengineering.

Speaker 2: 43:48

He's co-founded Btech Innovation, TrapTech, Earfit and AdPark companies that drive innovation and additive manufacturing across various industries. He specializes in managing multidisciplinary projects and tackling complex challenges, leading teams to develop cutting-edge additive manufacturing products and services that disrupt traditional industries. But wait, there's more. He has been recognized three times in Fortune's 40 under 40 list. He has deep technical expertise in SLM and EBM technologies, along with extensive work in material science. All of his companies operate at the intersection of deep tech and additive manufacturing, collaborating with industry leaders such as Materialice, Forum Labs and Top to push the boundaries of innovation. So we're thrilled to be able to introduce Kuncai and look forward to your conversation.

Speaker 5: 44:48

Thank you very much, greg. So good morning and good evening for everyone. You very much, great. So good morning and good evening for everyone. So my name is Kunzai and I'm coming from mostly the engineering part, both in the aerospace and the medical side, so I have started the medical 3D printing business in 2012. So it's been more than 10 years that I've started the medical 3D printing and over the time today I will try to a little bit explain to you why the additive manufacturing and medical 3D printing intersects. But, on the other hand, we also have some challenges to use the technology in a more efficient way. So, on the TrapTech side, it's a spin-off company from the B-Tech Right. So on the TrapTech side, it's a spin-off company from the B-Tech. So we are actually roughly 50 people in the company, based in Turkey, and we are very much focusing on medical applications with titanium. We also have a dental unit inside, but we are also making a lot of research about the new biomaterials, which I will try to explain you today. So, um, as as I mentioned, so we are a tech company, but we are collaborating so many universities, both in the us and the uh and the europe, uh and germany, finland, uh, switzerland. Um, and actually we like to work with this way because we are learning a lot. You know, and we know that you cannot be expert of everything. So, um, our vision actually to use the additive manufacturing and the biomaterials technology to make the technology and the materials more accessible for the people. And I remember the dates where we started the 3d printing and then 10 years ago, and designing an implant would take like custom implant would take like two weeks or three weeks. Now, with the technology, it's more accessible. And I was also had a chance to work with the early versions of concept laser m2. It was one of the first installed base in in europe uh on metal editing manufacturing and and I remember how challenging it was to use a 200 kilowatt uh 200 watt laser slm machine. I also had a chance to work with evm machines. So it's much more complicated technology. But unfortunately, what we see in the market is that we say that, okay, it's like a press and push the button and get the parts, but it's not working this way. So therefore, we also believe that accessing the technology and using it in a more efficient way also makes a lot of difference and a personalized implants really needs that.

Speaker 5: 47:34

So what we do? We focus on different areas. So we are making custom-made implants. So we are. We have an iso 13485 certified printing center with multiple metal additive manufacturing units. We also have some bioprinting and peak printing and also some SLS and SLA technologies.

Speaker 5: 47:58

So we are making research on the biomaterials, mostly the biodegradable materials which I will mention. They're not commercialized yet, they're still under research, but we made a lot of progress uh, and we are developing process for different uh alloys, uh, and of course, the titanium different different titanium alloys also uh in our scope and uh, we're also working with some medical companies, uh by making some custom medical models for training and education purposes. So I mean, I want to repeat the information that the other presenter has done earlier, which were really great, and you know, we are also making some number of implants in the market as a number of implants in the market, um, and actually what we see is that each year, um, we see more and more demands, uh, but we also see that, um, that the manufacturer are not always aware of the problems that may occur in the long run or in the pulse process or even in the heat treatments. So therefore, I mean we believe that validation of the process is also very important, and not only that. I mean we know that titanium-6-4 is one of the most common material in the market, although it's not coming from really on the medical side.

Speaker 5: 49:26

It's more aerospace-based material but it's more easy to. It's available in the market and orthopedic industry is using it for a long time. But we have aluminum, and the mechanical properties are one of the best, but it's not the ideal, uh, and we know that the the biological behavior of the material also, uh, one of the best, but still it can be improved, um, so, and it's not a good material for that manufacturing. What we see is that we are having a lot of issues due to thermal warpage, like, like heat, um, overheating and and also like geometry change and everything. There are a lot of problems of using titanium in the additive manufacturing. Therefore, there are some other materials that are more suitable for using the SLM technology or EBM technology and they're absorbing energy in a better way.

Speaker 5: 50:23

So we are making some research about the new titanium alloys and also we are interested with magnesium material, which is also another biodegradable material. Magnesium is very explosive. Even getting the powder is very tricky and using the machine is also quite dangerous because it has a lot of crack problem and also it has a lot of smoke during the process. But there are some institutions that make some progress and now we are making some research about the fine tuning, the process optimization and process parameters, and also we are looking for the application areas in the orthopedic area which could be interesting. The other one is the polymer material that we are working on.

Speaker 5: 51:14

I mean, there are already some polymers in the market, but the problem is these polymers are either on the FFF types of printer they're working on the FFF types of printers or like a big carbon dioxide-based SLS technologies carbon dioxide-based SLS technologies. But we believe that these materials and technologies will be part of the point-of-care centers. Therefore, they should be used in the desktop kind of SLS technologies and today like a Formlabs or there are also some other brands in the market which you can purchase less than 20K and they're working very reliable. But of course, it's tricky to use these materials in these machines because the laser source and the wavelength on the carbon fiber lasers are different than the carbon dioxide lasers. Therefore, you need to use some spatial techniques or maybe nanoparticles to absorb the energy onto the material and get the demanded shape. So we are working with some universities, in this case so from Hungary, switzerland and Germany, and we have made some progress.

Speaker 5: 52:27

An idea here is, as I mentioned, to make this niche polymers, biopolymers available and validated in the desktop SLS technologies to be used anywhere in the world. Because the design technology is also making a lot of progress. We see more and more automated design processes and when you have these two tools design and the manufacturing then you may not be needing a lot of expertise or engineering skills to be able to print some custom devices in hospitals as well. So I also mentioned that the new types of titanium, the new types of titanium. So when the market grows, we see a trend of lower price on titanium powder.

Speaker 5: 53:21

But still, in terms of the mechanical properties, we start to see variations of so many alloys in aluminum alloys, nickel-based alloys or steel alloys for different applications. Therefore, we believe that in the future we will be seeing more options for trauma cases, cmf cases or orthopedic cases, and even playing with some heat treatments, parameters or process parameters, we can also end up with various mechanical properties which that particular application needs. So we are working on an AI-based process optimizer software. So this is basically, you know, the process parameter is very experiment-based uh knowledge, and so many people are doing the same stuff in the different labs and spending the same money for the same results, although there are now more and more knowledge and data and the literature, and now we're trying to gather this around and make an AI tool to end up with the demanded properties so you can use different layer thickness, laser scan speeds or even you can play with some alloy composition in case it fulfills to medical regulations.

Speaker 5: 54:51

So I think one of the very interesting points that we have seen in the presentation was the excess powder coming from the manufacturing. Many manufacturers are not even aware of this, I mean, and it's not visible unless you see it with an SEM or you do some tests. And cleaning the part is a challenge. And this Estabular cop was one of our first products and it was printed with the EBM and if you know the technology, ebm is a preheated technology and you have a lot of unmelted powder but they're like a cake, they're not free-floating powder and removing those powder makes it even more complicated. Therefore, I mean, for this cup, we look for so many options for post-processing, like a chemical or mechanical, but also validating the process, which means that you get end up the same results for each time. That's also another challenge. So, therefore, I think solutions that have been presented are really great in that regard.

Speaker 5: 56:04

So we are also looking for some alternative waves, and this was a study that we have done in Politecnico di Torino in Italy. So we have made some chemical process for nanotexture titanium surfaces, and this is a research at a PhD research actually, and it's, of course, the lab scale at the moment. It's, of course, the lab scale at the moment. It's a foreign project, but we see a lot of difference between the raw parts and also the process parts, post-process parts, and we believe that this is something underestimated in the markets and we will be seeing more and more research about that in the future.

Speaker 5: 56:53

And I think this is also part of the regulations, because on the MDR side, you need to have a clear validation process about how you make sure that each part are producing the same properties and also you clean the same way.

Speaker 5: 57:11

You don't have any excess powder.

Speaker 5: 57:13

So this is also, uh, another challenge of the technology has today. So, um, as I mentioned, so, um, we will come to a point to discuss about the mdr. So we have a c certification, um we received in 2023, 2023, uh, but um in the last two years, the last three years, europe is facing a lot of uh problems with the mdr regulations, since it's very expensive, you don't have enough experts all this are really crazy. And then we have decided to stop all the activities in in europe and now we are trying to switch I mean to US markets. So we are trying to create some partnerships and we have a long history about the research, about the mechanical part and the bio side of the additive manufacturing and we are hoping to find some partners to grow in the US market. So thank you very much. So, again, my name is Kun Tai and I'm one of the co-founders of TrapTech and if you are interested what to do or anything with our companies or in our regions, I will be happy to help. And thanks for listening.

Speaker 2: 58:32

Thank you very much, kuntai. I'm glad that you spoke about validation, and it's appropriate given our next speaker. I thought that was very interesting. In particular, the nanotextured chemical process. I'm sure we'll have some questions about that. One person has submitted questions in the Q&A section of the Zoom. Feel free to submit any questions that you have. We have one final speaker, who I'll be introducing shortly, but we will be able to address any questions. For those of you that have already spoken, if you have ideas for questions that maybe you think would be useful for the audience, feel free to submit your own questions, and it'll be a good way to get started for our Q&A when that comes. So, kyle, feel free to share your screen. Kuntay, what time is it right now in Turkey? Oh, you're on mute.

Speaker 5: 59:31

Yeah, it's 8 pm, 8 pm.

Speaker 2: 59:34

Okay, so thanks for staying late with us.

Speaker 5: 59:37

No worries.

Speaker 2: 59:38

Kyle's screen. Okay, it looks very good. So, again, we were just talking about validation, so we purposely save the best for last. All of these ideas are exciting and obviously present a lot of great opportunities for orthopedic advancement, but it's important in FDA's perspective, of course, for there to be the proper quality and regulatory safeguards in place. So I introduced Kyle Kovach.

Speaker 2: 1:00:05

Kyle is in Cleveland, ohio, and he serves as the quality and regulatory manager at JLX Medical. Jlx specializes in engineering support, specifically in product development, regulatory affairs and quality management systems. Jlx serves many types of clients, including startups, independent inventors, midsize and large size medical device companies not just 3D printing companies all of these companies of which are developing class one and class two medical devices in the medtech industry. With over 13 years of experience in biomedical research and medical device quality and regulatory affairs, kyle has played a key role in securing numerous FDA clearances for JLX clients. He has successfully led FDA submissions, including 510Ks and pre-submissions. I see his colleague Stacey on our call and I'm sure that there's quite a few other folks that are very eager to hear from Kyle. So, without further ado, kyle, we look forward to your talk.

Speaker 6: 1:01:12

Great. Thank you for the introduction. Appreciate that. Your talk Great. Thank you for the introduction. Appreciate that, like you said, my talk here is going to be a little different than what we've heard so far more on the materials and design side, it's going to be a little higher level, specifically talking about the regulatory implications for these devices. So thanks for everyone who joined the talk. Appreciate you hanging on to the end here. Hopefully you learned something and find this piece of things valuable.

Speaker 6: 1:01:43

So I won't rehash all of the intro, just to give a little brief background of myself and sort of give you a perspective of where I'm coming from relating to the 3D printing field. So I do have a biomedical engineer. By training at JLEX, I obviously have focused more on the medical device quality and regulatory side of things, and so I do have a lot of direct experience in, like Craig said, leading FDA submissions like 510Ks, de novos and pre-subs. Again, quickly, just to talk about what JLX does and sort of the reason that we have a lot of expertise on the regulatory side of things. We do have an in-house engineering team that does design and development. Again, we have regulatory affairs and quality engineers as well, and so we do work with companies of all sizes anyone from single surgeon, inventors, startup companies to obviously mid and large size corporations as well that need help with our services, and we work really anywhere in the product development lifecycle for medical devices, from initial concepts all the way through commercialization. So in terms of 3D printed implants, I highlighted sort of three main areas here that we at JLX work a lot with. The design and specification piece of things I'm not going to focus on in my talk here. I'm going to be talking more about again regulatory affairs and process validation as well. You'll see in some of my later slides here how process validation really is a key, key piece of the regulatory submission and clearance process for these types of devices.

Speaker 6: 1:03:40

So I guess to start at sort of a high level here, I want to talk a little bit about the different regulatory pathways that are available for all types of devices, but obviously specifically 3D printed ones as well. I think the first thing that's important to note here is that the type of pre-market submission that ends up getting submitted to FDA for an additive device isn't determined by whether the device is 3D printed or traditionally machined. It's determined by the regulatory classification of the device type itself. So whether that's a spine implant, a hip implant, an extremity bone screw, whatever the specific device type is, determines the classification, not how it's manufactured. So the first type of regulatory submission that the majority of class two devices in the US fall under is the 510k pathway, also called pre-market notification, and so in this pathway, you are essentially identifying a device that has already been cleared on the market and demonstrating that your device is substantially equivalent to it. Demonstrating that your device is substantially equivalent to it. It carries a 90-day FDA review time and again. This is the pathway that the majority of Class II devices take to market. The other alternative pathway is the de novo pathway. This can also be used for Class I or Class II devices, and this is for more novel devices, so things that are so new to the market that nothing has ever been cleared before. That is exactly like it. In this pathway, fda will actually create a new product classification. It is a substantially longer, 150-day review time, actually often longer than that due to all of the questions and clarifications that FDA needs about the device. But that is the other main pathway to clearance for class 1 and class 2 devices in the US.

Speaker 6: 1:05:49

The last thing that I want to talk about on this slide here is the Q-Sub program. So this isn't a pathway directly to market clearance, but it is a specific program that FDA offers where submitters can actually get formal FDA feedback, have an interactive telecon with FDA before they spend all the money to actually submit one of the clearances we talked about before, so the 510k or the de novo submission. There's actually no FDA submission fee involved with the Q-Sub program. So this is something that we do a lot of at JLX. We encourage our clients to take advantage of it, specifically if your device or your development pathway has specific questions or challenges that you want to get FDA input on again before you submit that regulatory submission. So taking, I guess, a step forward.

Speaker 6: 1:07:12

Here are a number of different general topics of information and documentation that then go into those submissions to FDA. This list certainly is not all-inclusive. I highlighted the ones here with asterisks that I think are particularly important to focus on for 3D printed devices. So mechanical testing, obviously key for any orthopedic implant, but specifically for 3D printed ones, I've highlighted an FDA guidance document on the right here this technical considerations for additive manufactured devices. That is a wonderful resource for all kinds of 3D printed devices, so multiple materials. It's not specific to an anatomical region, but that gives a lot of good information on FDA's thinking and expectations when it comes to 3D printed devices. And there are also many device specific guidance documents out there that you can look at. You know, whether, again, it's a bone screw, a spine implant, there are guidance documents out there specific to those types of devices. Engineering drawings that you include in the submission for 3D printed devices. There are things like porosity, lattice structure versus solid printed areas of the device that are important to call out on these engineering drawings that aren't a factor at all for traditionally machine devices. So that's an important consideration.

Speaker 6: 1:08:51

Material characterization and the manufacturing process material characterization and the manufacturing process. We'll talk more about the manufacturing process, but with 3D printing being a relatively new technology, again, compared to traditional machining, details of that manufacturing process are something that FDA pays a lot more attention to in these submissions. And then biocompatibility is the last one I'll end up talking a little bit more about later, but for 3D printed devices this would involve biocompatibility both of the material itself but also considering the effects of post-processing cleaning and removing of manufacturing residuals that I think actually a couple of other presenters have touched on here today, so what I want to move on to here is talking a little bit more specifically about some of the pain points that we have seen with our clients' submissions our clients' submissions specifically for 3D printed devices. What I want to lead with, though, is that FDA's thinking and outlook on 3D printed devices is continuing to evolve. Month by month. Year by year it changes, and obviously another thing to keep in mind is that any unique submission to FDA does involve a degree of reviewer subjectivity. So I think sort of one of the challenges that we have at JLX a lot of times is a lot of people tend to look at FDA as sort of this machine that you feed a submission into and it spits out a clearance on the other side, and obviously that's not the case. There's a human review team, there are educated scientists on the other side that are looking at your submission, and so it's our job to clearly present sort of the device, the underlying data and our arguments for it, so that these people on the other side can look at it, understand it, and it is meeting the requirements that they have for a safe and effective medical device.

Speaker 6: 1:11:06

So some of the topics here that we have found have been a challenge specifically for 3D printed devices. One of them is ensuring that there are adequate details of the manufacturing process defined in the submission. So one example would be specific 3D printing machine information that you're using. So FDA wants to know make model number of machines, like the exact details of the machines that you're specifically using and validating to create your production devices. Worst case manufacturing conditions is another one I've called out. One pretty easy example here would be build plate positioning. Obviously there are a huge number of different parameters that you would need to consider, but you need to be able to define your worst case manufacturing conditions with data and show that to FDA.

Speaker 6: 1:12:06

Performance testing another key one I've called out test coupon testing. Here that's something obviously specific to the 3D printing world that doesn't exist and isn't really relevant in the traditional manufacturing world. But having test coupon data and how that relates to your process validation is important in regulatory submissions. Manufacturing residuals this has been much more of an FDA focus lately, specifically the removal of particulates from the product after it's been printed. So this is again a biocompatibility concern and we have seen much more FDA focus on this in the recent years than perhaps they did maybe a handful of years prior and the last one is build process validation than perhaps they did maybe a handful of years prior, and the last one is build process validation.

Speaker 6: 1:12:58

So I'll actually dedicate the slide after this to process validation. But this is sort of, I guess, the overarching theme of needing to include all of this other information in the submission include all this other information in the submission. So process validation is something that, for a medical device manufacturer, you need to be validating your processes anyway per FDA's quality system regulation, so 21 CFR 820. But, specific to 3D printing, it's important that you clearly define all of the build parameters and are validating your process. So, again, you can show FDA with data that your build process is able to consistently reproduce your printed device across build cycles. So it's great if you can print one device, mechanically, test it and it passes. Your test meets all your acceptance criteria. But FDA wants to be convinced that your process is able to repeat that over time reproducibly and reliably. And so the last thing on this slide that I want to make note of is that anytime you have a validated process, any changes to your device, changes to the process or process deviations that you see you need to be taking those into account to then determine if you actually need to revalidate the process later on down the line. Later on down the line.

Speaker 6: 1:14:35

So I'll finish up here with a quick case study. So this is an example of a client that we worked with at JLX. This clearance was very recent in 2025. It was a 3D printed titanium spine implant that took the 510K pathway. So we identified a predicate device on the market that we were substantially equivalent to, and there were a couple, I think, key success areas that were important for this submission, one being we were able to get very detailed and comprehensive process validation records from the contract manufacturer. And also there was a lot of key discussion with FDA on the lot release criteria that were defined for the 3D printed devices themselves. So those were sort of what I'll call the sort of keys to success of this submission and getting it cleared by FDA. So that's all I have for you. Again, I know this was a little bit different than the other presenters here today, but I hope everyone found it valuable and I appreciate your time.

Speaker 2: 1:15:52

Thank you very much, kyle. So, as I plugged a few times, I'll repeat one more time that JLEX and Restore and HyMed are all going to be exhibiting at AAOS in just a few weeks, from March 10th to March 14th. By coincidence, we're all exhibiting literally a few rows from one another, right between the large Smith and Nephew booth and the large Zimmer booth. So for those of you that will be in San Diego next month, we hope that we can continue the conversation in person Until then. I'm happy to see that a number of questions have started to come in through the Q&A. So, for those participants in the audience or again for those speakers, if you have questions that you would like to submit, either for yourself or for another speaker, feel free to do so.

Speaker 2: 1:16:43

I'd like to begin the conversation focused on Nathan and Nathan. I thought it was interesting. You know, kind of looking forward. I really like the slide that you had shared as far as the different disciplines for porous 3D printed implants, acknowledging that spine is most established, extremity is growing and trauma significantly behind. If we were to have this webinar, say, in five years from now, how much more growth do you expect in spine? Do you think that the market for spine is more or less established. Is there more opportunities and do you expect for extremity to continue to grow at maybe the rate that we all saw spine five years ago?

Speaker 4: 1:17:22

Yeah, yeah, great question. I do think there's still opportunity for spine to grow. I think some of the fusion market is maybe reaching a point of saturation with regards to the use of additive, but there's some interesting companies out there. I'll just highlight one of them, Carlsmed, who is pioneering the use of additive manufacturing to deliver patient-specific spinal implants. So, whereas spine has been the leader in using additive for the introduction of porosity and to promote fusion, there really hasn't been a whole lot in spine as far as patient specificity, whereas the other areas are actually using additive mostly for the patient specificity. So I think there is opportunity in spine. I think Carlsman is doing some really interesting things. I think there's a few other startups that are also looking at a similar space. It's something we've taken just a brief look at, but that's an area, I think, of absolute potential growth in spine beyond the fusion market. It still is the fusion market, but it's kind of a different angle to it, if that makes sense.

Speaker 4: 1:18:19

And then the extremities absolutely I think those are just getting started. To be honest, particularly in the large joints If you look at, you know knees and shoulders, the total ankle market. I think there's a lot of room because additive solves two things. There Again, the patient specificity, which I think the data is pretty compelling of why that leads to better outcomes. But then you have implant loosening in some of the large joints. That is a big problem and the surgeons want to get away from cemented implants oftentimes and utilize porosity to improve fixation. So I think there's a lot of reasons why we'll continue to see the use of additive grow in the extremities market.

Speaker 2: 1:18:57

So Garen, who has since joined me, and we now can prove that we are in fact in the same building. We were both at the Hospital for Special Surgery last fall and we got into interesting conversation about patient-specific implants. And you know, I could certainly be convinced that. You know a customized implant is going to perform better than an off the shelf model, but at the same time there's costs that are associated with that. Maybe as engineers we don't see that directly, but insurance companies certainly would Question. Both for Nathan and then for Kuntai. I'm curious in your opinion, if you're able to comment on patient-specific implants, at what point do you see a patient being eligible or that circumstance warranting that additional customized implant? Versus when is an off-the-shelf implant still a viable solution?

Speaker 4: 1:19:52

It's a great question. I'll start and then, kutai, please jump in. You're right. The pushback we get on the use of additive in our patient-specific implants is cost, and then also speed, because there's a lead time associated with it. Off the shelf by definition it's sitting there on the shelf, right, patient-specific. There's a lead time associated with going from a CT scan to an implant, and so both of those things I think the last part of the talk that I kind of just highlighted, and if I drop my slides in, you'll see that those are two of the biggest areas, I think, of opportunity, the third being what Kyle touched on is improved regulations and consistent standards, et cetera.

Speaker 4: 1:20:30

But the point, you know, where it makes sense, I think it depends. I think you know, in this space of like you're facing, you know, the patient with truly no option you're facing, say, an amputation. The willingness to pay there is extremely high because the alternative is so dire and bleak. Right, then something like a total joint where it's like off the shelf versus patient specific. The data is compelling but at the end of the day it's still a total need. For example, I think the willingness to pay is a lot lower and so cost needs to be more neutral there, like we've got to find. But the technology isn't is growing so quickly. The printers are getting faster, the qualifications are getting better. On the digital side, there's a lot more automation on things like segmentation, whereas I think we're going to see in the next few years that or we're starting to realize it now, to be honest where the cost of goods are somewhat equivalent and the buyer will become indifferent then and simply is picking the best technology. Maybe not quite there yet, but that's absolutely on the horizon.

Speaker 2: 1:21:27

Excellent.

Speaker 5: 1:21:28

Do you have anything?

Speaker 2: 1:21:29

else to add?

Speaker 5: 1:21:30

Yeah, I agree with Nathan. I think that the cost and then who is paying is, I think, yeah, I agree with Nathan. I think that the cost and who is paying is, I think they are the most important points to decide about it because it depends on the market. But if the conventional implants are reimbursed and custom implants are not, then the decision is very clear that it's only used when it is really really needed or you don't have an alternative. It also depends on the, I think, the surgeons. Some surgeons, um, finds this easier. Some surgeons believes that it's still, uh, you know, not matured enough and you know there's still uh risky or a space technology that should be used in the very rare cases, uh. But I think we're seeing more and more people, specifically young surgeons, are showing more interest than the very experienced surgeons and, together with the involvement of technology, I think that will be a little bit more tricky to decide. I think we will be seeing that more primary cases will sights on custom implants in the first attempt.

Speaker 1: 1:22:39

Craig, I'm going to add a little bit on the market growth and also patient specificity. Market growth, first of all. I mean we're hearing that the spine is questionable. Saturation I don't think it's going to saturate. Just from the clinical perspective, we have our aging population that has more and more people who not only have bad back but also failed back surgery. There's for all those fusion surgery that we're talking about. There is this one case, one disease called adjacent segment syndrome, and that's a repeat client and also means whatever we have right now aren't working. We're not really solving people's back pain problem and that, you know, everyone is going to experience one time in their lifetime. So that's definitely a growing market. But whether or not 3D printing is going to penetrate that, that is the question. But whether or not 3D printing is going to penetrate that, that is the question.

Speaker 1: 1:23:36

The other thing through my research very recently about patient-specific versus adaptive implants is you know these robots, they can actually modify intraoperatively of how the bone is cut. So it's not just the implant that has to be patient-specific, the procedure itself can actually adapt. So the question is how useful is it? For a 100% personalized implant? It really isn't necessary and we actually saw a couple of startups recently pitching through and one of them actually is just like restore 3D, complete personalization, and we have some surgeons in the audience and this question is raised again. I think at some point the cost of manufacturing these personalized implants if it goes down and the benefit the clinical benefit actually really is there, then I think we're at an intersection where this is going to take off. That's my opinion. I think the majority of the clinicians, like Conte and some other speakers, I think they're still kind of favored off the shelf because we're not at that intersection yet for many of these implants. That's my opinion.

Speaker 2: 1:24:59

So Jenny just got back from AM Strategies, so I would imagine that a lot of these topics were discussed and I'm not sure how was that event this year? In that they typically try to, I remember at last year's event they presented challenges that all industries face, right Recognizing that not everyone in the bio sector is in that audience, and I thought it was quite interesting to see. I'm curious in your opinion, how did that event go this year and were you able to get into conversation about patient-specific implants with folks that were in attendance?

Speaker 1: 1:25:34

You know it's a biased audience. Needless to say, everybody loves 3D printing, including myself, and the only reason why I said what I said it was I try to provide a counterpoint over. Things can grow and improve. I think the technology still to be mass producing and high penetration and adapted by the clinicians. There are a lot of technical improvements that on our end we need to provide and I think we've seen a lot of technical advancement in the last couple of years, including this conference, but there's still a lot of work to do. That's basic. I think the conference itself didn't address healthcare that much. A lot of them is industrial, but obviously if you're in 3D printing industry, then you're definitely a fervent supporter of personalized medicine for everybody.

Speaker 2: 1:26:24

Excellent. Well, I had a question that was emailed to me to ask to Garen and I'm about to get to that. But I want to get back to Kyle, just in the context of patient-specific and personalized implants. So Ryan Menrath asked a question in the chat what would the qualification look like for a personalized orthopedic implant? Does the FDA allow for a part family qualification? So personalized implants are not hampered with many individual qualification efforts. Now that question came in during Nathan's talk, but I'm curious from a quality perspective, kyle, maybe you're best suited to address that one.

Speaker 6: 1:27:02

Sure, I will qualify this by saying this is certainly a question that the actual answer is going to be specific to what device it is. But I think at a high level we've seen that certainly qualifying or getting clearance for a family is possible. We've seen for certain types of devices, fda wants you to define sort of a design envelope, so like, what are the bounds of what you would possibly be printing for a patient-specific implant? And then obviously, like I talked about in my slides, you would need to do a very good job of defining what exactly is the worst case device and then performing all of your testing on that worst case design.

Speaker 2: 1:27:54

Anyone else have anything to add to that?

Speaker 4: 1:27:57

Yeah, from our experience I think what Kyle said is right on it's defining that design envelope.

Speaker 4: 1:28:03

Even though it's patient-specific, you are still operating within the abounding box of dimensions from a design perspective, but then also the constraints then from the manufacturing perspective, because they want to ensure that if you're printing something outside of that range bigger, smaller et cetera that has been qualified and so you do establish those envelopes and the worst case for the actual physical manufacturing might be a different worst case device from the device specific testing, and so it can become pretty complex the device-specific testing and so it can become pretty complex.

Speaker 4: 1:28:37

And the one thing we've noticed with the FDA is in patient-specific, when you have a lot of dimensions that can change, it can be very difficult to define what is worst case, and so you often have more than one worst case device. I recently ran a fatigue test and with the FDA we kind of agreed that it was very difficult to tell what would be worst case, and so in our bounding box we actually established four different worst cases. So that adds a lot of cost and time. It could become quite expensive, but it's the reality. You can maybe use FEA to try to model some of that. But yeah, there's a lot of complexities, but in a sense that's the way that we've kind of seen that play out with the FDA.

Speaker 2: 1:29:13

Thanks, nathan. So I want to bring Garen into the conversation now and, as I said, there was a question that came in from someone that's used MCD. They sent it via email so they said I'm on the presentation that, as you mentioned. Thanks for sharing. We've been internally testing with your material. One thing that we have not really discussed is with fatigue performance. You mentioned 50 percent, and this is directed again to Garen. He mentioned 50 percent improvement using high-med blasting material. Was this comparing non-HIPT, non-blast product to HIPT and blasted with high-med material? He's curious to hear more.

Speaker 3: 1:29:50

Yeah, yeah. So thank you for that question. I guess I can always reply to this email too, but I'll do it on the call here. So those parts that we've gotten from customers were printed and hipped versus printed, hipped and high med blasted. So they were SLM printed, which I think in most cases needs some type of treatment for stress relief and things like that. So that is what we've seen. I'm sure we would also see a great benefit from purely print plus blasted versus just print, but the experience we've had so far has been SLM printed and HIP processed and then both sides of blasted versus non-blasted.

Speaker 2: 1:30:28

Excellent, thank you. So, kutai, I'm glad that you were talking also about a form of post-processing and I think it was in the slide that you shared also nanotexturing, and I used that really as a segue to Kyle when we were talking about validation. So, when you discuss validation and reproducibility for that nanotexturing, what type of tests and sample size would you recommend of tests and sample size would you recommend? Is that something that um you establish on your own? Or what level of of consulting, perhaps within your organization or external uh, would you consider or would you need to consider?

Speaker 5: 1:31:05

yeah. So, first of all, this is a phd study of a student which actually uh, warned me to not to reveal so much information for now. Uh, so, but it's, it's a I can tell you that it's a little bit beyond the commercial application, yet it's in the lab scale. Uh, they have different kind of um, I think, chemical process that's of um, uh, hip cup. So we want to have that to, to show that the you know, the conformal surface uh to to you know, make it more realistic, because we you end up with a different results if you have a flat surface around the surface. So, therefore, we have taken a hip cup and then we cut it and then, uh, they are using this um, real hip cup for this, you know, as a specimen in the study. That's. At this point I can say excellent, let's see.

Speaker 2: 1:32:09

Um, so a question for kyle. Uh, kyle, do you question was really just as far as JLX's business strategy. Gilead is wondering if you need to visit the submitting company or are you able to prepare a submittal 100 percent remotely? And if remotely, how do you learn and validate what the company is reporting? What does that arrangement look like when you're working with clients on a quality and regulatory project?

Speaker 6: 1:32:38

Yeah, good question. We can certainly do it all remotely. That's actually what we do most of the time for putting together a regulatory submissions. That said, we can certainly visit on site if that's what the client prefers. If there's things that you know would be worth seeing in person you know we've had people ship us part samples. You know we do video calls to see the device physically, we can do that on site, but usually it's for the regulatory piece of it. A lot of it is just documentation based, and so it's really just figuring out what a file share system is. We can communicate pretty clearly the types of documents that we expect, whether that's, like I said, engineering drawings, test reports, validation records, all of those things you know we can share remotely, view remotely and communicate back. You know, if we think there are issues here, gaps that FDA would need to see filled. So, yeah, it's a pretty easy collaboration on the regulatory side of things.

Speaker 2: 1:33:48

Okay, thanks, kyle. We have a great question from Brett and I know I'll be seeing Brett in a few weeks. I think we've seen each other every year when we are at AAOS, but this question is addressed to Kuntai, I believe. So. Is nanoparticle debris contaminating the bloodstream a patient risk? To what level does validation and testing help manage this risk effectively? And then the second part to the question he wants to know how does FDA regulation for device manufacturers help to mitigate the patient risk?

Speaker 5: 1:34:23

Well, I think the animal testing. I believe that's one of the best methodology that we can test it. There are some experts that's choosing the rights, the material methodologies and the animal types that you understand this to validate it. It's not actually a part of the validation process of MDR or the CE certification. It's more of, I think, a new device or a more I think Kyle will answer it differently, but it's not a validation of the certification, but it's a process of how safe the device is. I believe.

Speaker 2: 1:35:05

So, kuta, you do a lot of work. It seems like partnering with academia, and there's a specific question Sahin, who I apologize if I'm mispronouncing your name wants to know as a candidate of entrepreneur from Turkey, would like to ask why do you partnership with academia so much instead of conducting all of your R&D studies in-house? What is the benefit of?

Speaker 5: 1:35:34

this additive manufacturing company groups in orthopedic? Probably it's because I do not have 1,000 people. So when you get into deep tech you see that there's so many topics that you need to understand and have some expertise on, but you cannot do everything by yourself. So you know it's like a heat treatment is all scientific stuff and the surface is totally a lot of structures is you know all different area, mechanical properties, process. I mean, you cannot do them all and it's not our job. So we are not scientists, we are, in the end, entrepreneurs and what we are doing is that collect the right information or data and people around and try to make a commercial product. So it's not in our interest to know everything. So what we are interested in is to develop a product that works and competitive. In order to do that, to get some people around.

Speaker 2: 1:36:34

I thought it was a question that needed to be addressed because there's a lot of students and Jenny, you could attest to this right. This is an event that is broadly produced for orthopedic 3D printing. Not everyone in the audience, I'm sure, is involved in this field. Maybe there's some folks that are still completing their studies and they're looking to find opportunities. But you're absolutely right. I think the bridge between academia and industry is maybe the scale, and certainly academia as far as being able to do research that inspires larger research. I would really defer to Nathan on that one. Right. It seems like Restore3D has close ties to university as far as how your company was first established.

Speaker 4: 1:37:18

Yeah, we do. We were kind of a little bit of a spin out out of Duke University, which I think, garen, you're an alum of right, so our founders came from there but then close ties with many academic institutions, I think you know just that basic science, collaboration early on, access to equipment that just we don't have. And then, to be honest, there's a little bit of a marketing thing to it. There's a maybe a skepticism with research published by industry because it's maybe conveyed as being a little biased or whatnot, versus if it's coming from academia it maybe is received with a little higher regard, and so I think that that's a reason as well as just that kind of credibility factor to it maybe is received with a little higher regard. So I think that that's a reason, as well as just that kind of credibility factor to have like things that are published in the academic literature from universities.

Speaker 2: 1:38:05

Jenny, how are we doing on time? I'm sure you have some questions.

Speaker 1: 1:38:07

Time is good, but I actually have a question on my own. So I see SLM process is being, you know, the dominant force for the Meadow implant. But I've been hearing EBM quite a bit lately, including some of the pitches I'm hearing. So I'm kind of curious does EBM really change the game significantly from your perspective? From post-processing to designs, to Nathan, your goal is to create this whole workflow. Have you guys thought about these new processes in Kyle, you know, regulatory-wise, like does EBM? I think there's some new technological advancement in EBM and that's why I've been hearing a bit for both Europe and US. So I'm just kind of curious where things are with that particular process.

Speaker 6: 1:38:53

Yeah, I guess I can, I can add my perspective on it. We certainly have seen not as much on the EBM side from our clients that we've been working with, so I won't say that it's unheard of in the regulatory space. As far as what's been cleared out there, you know, I think we'd probably. I think, like some of the panelists have talked about, there have been many more clearances in spine. So if we were to start digging deeper into that we would probably look at the spine clearances first to see if that manufacturing method is more prevalent there. But at least in my experience it doesn't come up as much through the contract manufacturers at least that we've been working with.

Speaker 5: 1:39:43

So Garen maybe you go first Well, maybe I can add a comment because I started to work with the R-CAM in 2013, and back in the days the EVM was very popular in the orthopedic industry. Actually, one of the reasons was you can use more coarse powder. In the days the EBM was very popular in the orthopedic industry, actually, one of the reasons was you can use more coarse powder in the EBM, which was cheaper back in the day. It's almost half the price of an SLM. But EBM is a very, very complicated process. I mean, the parameters inside the machines are insane and even the Arkham. People don't know what is doing what and it's just you change something and 10 other things changing at the same time and nobody knows how to control it. It's very efficient.

Speaker 5: 1:40:28

Back in the days, stacking was really something new and you know the powder was very efficient and you know you don't need a heat treatment normalization. I mean you see less or pitch because, um, the delta between the preheating and the melting as is lower. So and the the another difference was uh, you can use a higher energy because the energy energy penetration depth is higher. Uh, I mean, on on the SLM side, whatever power you have, the thickness that powder go in efficient is limited. In the EBM it is higher but you end up with a coarser surface of gas. But the idea was back in the day is that it's even better for orthopedic purposes. But today what I see is that the SLM machines are becoming more and more reliable and they're easier and the powder price dropped a lot.

Speaker 5: 1:41:29

And the Asian players. The machines are very productive. Now we have six 10 lasers working simultaneously and they're doing quite good. And I think after the acquisition of Arcam with GE, the company's focus shifted a little bit into the aerospace and I believe that we will see less and less EVM in the markets in the future markets in the future?

Speaker 2: 1:42:04

Jenny, I remember this was a topic of discussion at the in-person 3D Heals event that coincided with AAOS last year and I was going to ask Garen, because he presented a slide that I presented at that event and it was sharing some really interesting data that Royal National Orthopedic Hospital had performed. And little did I know. You had invited Johan Henkel and he was sitting in the audience and that's how we first came in contact. But maybe, garen, you could speak to the evolution of apoptotic abrasive at Hymed. This is a material that was not developed intending for post-processing and there's been studies that Hymed has involved in both for EBM as well as for other styles of print, but the goals are not always the same. Maybe you can just speak to the evolution of the abrasive and by post-processing, just on a broader scale, what are some of the common requests that you field?

Speaker 3: 1:42:56

Yep, yep, great question. So really, mcd, the apathetic abrasive. It was well before 3D printing and orthopedics was a thing right. So the company really started with requests for hydroxyapatite plasma spray coatings. And before you do that spraying you need to texture the implant so that you get good mechanical interlock with your HA coating to your part, so that it doesn't come off in vivo. And so we needed to texture the parts beforehand, and so the company developed this MCD, or this apathetic abrasive for usage before applying the HA coating.

Speaker 3: 1:43:29

Fast forward a little bit. A lot of our customers will just use that apathetic abrasive. Others will use the apathetic abrasive with the plasma sprayed HA on top of it, specifically for 3D. We've seen in the last five to 10 years a lot of growth there and the requests have been different. It depends on the customer. Some recognize these partially centered beads and say I need that all cleaned up across the entire body, and other customers will come and say, hey, the up face versus side faces versus other faces on the build platform look a little different. I see some layer lines, I see some build plate irregularities and we need those specifically cleaned up, in which case we'll focus our automation to post-process those areas to get a more uniform yet textured surface over time.

Speaker 2: 1:44:15

Very good. So I want to transition the conversation to materials. I know that quite a few of us in the panel are material scientists. There's a question that came in that I'm going to be addressing. I think this is probably best geared, maybe, to Kuntai, but I want to first start off Kuntai. You were talking about magnesium and I'm really happy. I think, jenny, you did a really good job finding a proper complement of speakers, not just for the market within orthopedic, but the material. So, kuncai, maybe you can speak a little bit more about magnesium. I know you know, as we acknowledge, there's a lot of work that your company is doing in academia. Do you see significant opportunities for growth for magnesium in an industry?

Speaker 5: 1:45:00

It's hard to say. I believe it will be still a niche application because it's not because of the magnesium itself, it's more about the process. I mean, in the past we used to see more people interested with the magnesium, but the safety started to become a very important topic. Even I think right now is no um company who are producing magnesium powder in europe. Uh, so yeah, that they they require very uh strict safety rules to produce such kind of materials. So, and historically, um, I mean, was a very interesting material for a lot of people because it's the greatest in a level. But I believe that it will be a niche application where some specific companies or institutions are able to print in a level, and then maybe there are some more and more applications will be visible in the market, but I do not see that as a mainstream material.

Speaker 2: 1:46:08

Thank you for your thoughts there. So Orr's question, continuing along the materials trajectory wants to know and I don't know who this was addressed to, because it came in during the Q&A, so we'll consider it a jump ball whoever wants to feel this one? How do you envision the future of titanium customized implants in an era where polymers are rapidly advancing in material properties, ease of use and even in-house manufacturing capabilities? So who in our panel feels comfortable speaking about polymer versus titanium 3D printing?

Speaker 5: 1:46:45

Maybe I can speak a couple of words. So clearly, the polymers are interestingly growing the peak and some other or some new materials are coming. But it's not just about the properties of the materials. It's about how confident is the user. Uh, is you know about the material? So titanium is in the market for a long time. They know what's happening with the titanium in 10 years, 20 years, 30 years. So for surgical applications, I think it's not very easy. A new material come up and everybody will say that, okay, this is great, now we will use this material instead of turning the material like a titanium or something. So it will take time. Uh, clearly, the the polymers has a lot of potential, but I do not believe in certain cases where really strength is important, that titanium will be replaced that easily. That's still, I think, the best strength to weight ratio material in the market.

Speaker 2: 1:47:51

You kept him waiting a long time, but I think it's really a question that probably is at the core of this discussion as it relates to osseointegration right, All of these materials naturally we're talking about need to be biocompatible. You know, the device could look cool and the pore size and print style could look quite appealing from a marketability perspective. But the question specifically relates to in vitro testing and he wants to know what are the best in vitro tests to forecast ASIO integration. So what are some materials tests that our panel is involved in, predicting how compatible and the level of bony ingrowth that one might see for these devices? It's such a broad question but it's an important question.

Speaker 2: 1:48:48

Maybe, Garen, we can feel this, perhaps representing HyMed, you know we manufacture these calcium phosphate materials. So not only are the post-processing processes things that we're performing with our automated systems, but we're manufacturing these materials. Our team is in the process of doing biocompatibility and cytotoxicity and bioburden testing, which we do on a frequent basis to evaluate how these materials respond in those instances. Maybe you want to speak a little bit more about material testing that needs to occur before a hydroxyapatite product is released at HyMed.

Speaker 3: 1:49:28

Yep, yeah, that's a good question. So we've done many studies. We talked about the embedded aluminum oxide or other materials that may be embedded as grip blast media in comparison to an apatitic abrasive, and we've done many SEM studies, both in-house and with independent third-party labs, to prove that no residuals are left on the part afterwards. So you have just your pure titanium alloy on the part. Additionally for something like hydroxyapatite coating, we follow ASTM standards for items such as tensile and shear testing, and we do that on a very frequent basis, as well as daily checks of things like crystallinity of our coatings, among other tests, to make sure that our surfaces and the products that we ship out are continually meeting and exceeding specifications.

Speaker 2: 1:50:15

Jenny, do you have anything that you'd like to add? I know you always have good questions and thoughts.

Speaker 1: 1:50:19

Yeah, I just want to add on the polymer versus metal set of things. I think we have hosted quite a few biomaterial conferences and what I have learned is that it is definitely a growing market where you can have biodegradable scaffolds that can encourage bone growth, for example for orthopedic purposes, or cartilage, both, for example, for orthopedic purposes or cartilage. However, the size of these you know, first of all it takes time for these biodegradation, and also the size. So you cannot have large defects and you cannot do like any replacement and stuff like that. So most of them are actually for smaller size of replacement or defects. So the size is a limitation.

Speaker 1: 1:51:01

But in the polymer side I think that that is the frontier I'm seeing as encouraging biodegradable scaffolds where the body heal itself, and there are a couple of companies working on it and the other interesting company I have seen last year actually Craig, you were with Alisa right and then her company, illuminate, actually has this interesting design of a particular screw where you can inject other materials. So I think in the future it's the design of implants itself can have other properties, like you can have drug illusion or you can coat it with medication or something like that. That would make metal interesting. So I think that's the material side of things.

Speaker 2: 1:51:51

Yeah, that was very interesting. And then also for those folks on the material side, I just shared a link related to ceramic 3D printing. Last year at this event in the fall, we heard from folks from Synaptic and my colleague Esther Valiant spoke representing Hymet and the recently established Bioceramic Center of Excellence. So I thought it was important to tie in that question for osseointegration once we focused on the materials, recognizing that as the underlying commonality. Anyone else in the panel that would like to speak? Maybe there's additional information that you feel is pertinent, given the direction that our conversation has gone?

Speaker 6: 1:52:35

I guess I don't have a specific answer here, but I would just sort of want to reinforce what I said in my slides, that FDA's thinking on this is evolving so quickly. They put out draft guidances frequently and although draft guidances aren't formally what they will be pointing to in reviews, if you read them it can at least give you an idea of sort of where they plan to go in the future. And in many cases the draft guidances, with some edits, end up becoming formal published guidances. So I would encourage everyone to sort of keep an eye out on those as they come out. They may be device specific. They may be specific to additive manufacturing. They may be device specific. They may be specific to additive manufacturing. Other ones may touch on biocompatibility for all types of devices. So even if you see something that maybe the title doesn't seem completely relevant to what you're doing, there may be bits and pieces in there that you can draw some important information from.

Speaker 3: 1:53:37

Kyle, if I can ask, how do you? How do you stay abreast of those new guidances? Are you guys just like scouring FDA's website once a week, or there's like some newsletter sign up for? How do you? How do you know when an applicable guidance has come out for you to review?

Speaker 6: 1:53:51

Yeah, good question. So through our work we do end up just seeing a lot of things through our searches. But FDA does have some very helpful email subscription updates so you can subscribe to get updates for specifically medical devices or specific centers within FDA. So we subscribe to a lot of those and they will just blast out. You know here are a bunch of different guidance documents we published. You know they have ones about recalls, about all kinds of topics. So yeah, that's an easy way to do it, that you don't have to actually go searching on your end. You can get it sent straight to you.

Speaker 1: 1:54:29

Kyle, do you see more European implant company coming to you guys after the MDR is implemented?

Speaker 5: 1:54:35

Yes.

Speaker 1: 1:54:38

Okay, that's a definitive yes okay, that's a definitive yes.

Speaker 6: 1:54:46

We certainly see um clients from europe, others from other international markets. Um, we have heard the general sentiment that mdr is challenging um, I won't say that. Everybody comes to us and says you know, that's the reason we're entering the us market, um, but I would say the prevailing sentiment out there is it is challenging. I think, like some other people have touched on here today, it's a lot of understaffing, I think, on the side of the notified bodies and you know they're just not able to get through a lot of these applications very quickly. And you know, not placing blame on either side, it's just that that's the reality of what's going on.

Speaker 4: 1:55:24

Kyle, can you comment on with the current administration here in the US, if there, and the changes? I know there's been cuts to the FDA as well as CDRH. Do you anticipate challenges with regulatory submissions or delays in timelines in the US in coming weeks or months?

Speaker 6: 1:55:44

Yeah, that's a good question. Obviously I don't think through what I've read. I've seen it has the layoffs have hit CDRH. I don't know anything about raw numbers or percentages. You know concretely which is. You know concretely. If I had to purely speculate I would say potentially some delays. But it is complicated because FDA is held to their you know performance goals based on law. So it's hard to say how that's going to shake out. You know, I don't know if they're going to be trying to hire more to backfill or how that's going to work. I wouldn't be surprised if there are delays. But again, that's, that's sort of pure speculation. All I can say is concretely, from the submissions that we've been working with this year, for example, we haven't seen any delays yet. So that's at least good. But obviously a small sample size.

Speaker 1: 1:56:44

Well, thanks for that I suggest we all go on to Twitter to tell Elon don't cut this particular segment of the government. I actually think that's going to work. You know, we just have to like, group together and be unified front.

Speaker 5: 1:57:00

Don't cut this part.

Speaker 3: 1:57:02

You can cut everything else, but just not 3D printing, okay, I also just wonder aloud here, kyle if there's a performance metric to be met of 90 days or 150 days and you have less folks to do it, does that mean that the quality of the review or the depth that they go to does that change to still meet their metrics right, and what impact does that end up having to device manufacturers, patients, surgeons, etc.

Speaker 6: 1:57:27

Yeah, I agree, and obviously that's a kind of scary slope. You can start going down. You know I, at least our interactions with FDA have always been. You know, these are like professional scientists on the other side, right, and like they are deservedly proud of what they do and, you know, obviously play such a key role in maintaining public health that I would hope that you know that that depth of review and the quality of their work isn't the thing that gets sacrificed. But obviously I guess, I guess we never know right.

Speaker 1: 1:58:03

I think the delay is going to be more likely than decreased stops, which neither is good.

Speaker 4: 1:58:10

Right, there might be other mechanisms, kyle, that they can still meet their metrics and yet still have delays, like using additional information holds more liberally, or something. Sure Good point, who knows? Who knows, though? I guess that's what we're all saying, right?

Speaker 2: 1:58:26

I thought that your 3D Heels interview was really interesting. I was reading it while you were presenting and it made sense the backstage conversation that we were having how you met Jenny some 10 years ago so 2013, thereabouts is when you started your company. Here we are, 12 years later. What has surprised you, right? I mean just being an entrepreneur, let alone being nominated three times for a Fortune 40s under 40,. Maybe you could speak about your entrepreneurial experiences in 3D printing, about your entrepreneurial experiences in 3D printing.

Speaker 5: 1:59:04

Well, I mean, I also read when you wrote back to the chat site that I was young. I was young and I didn't see that risks ahead, and then I was just running out without knowing what's expecting in the future. So I think 80% that what I expected didn't happen. So, but being an entrepreneur is like being on the road. I guess you find a way at least. I mean, I had big dreams. I knew nothing about the regulatory, so back in the days my thinking was okay, there was like a product, there was a buyer, then it should be okay, right. Then I a product, there is a buyer, then it should be okay, right. Then I noticed that, well, there's something called CE marking and it's very complicated and I knew that FDA is a little bit scary back in the days. But today, the regulations in Europe, I think it's not supporting innovation. So that's the biggest challenge I think that Europe will face. Nobody, I think, will push themselves and spend millions of dollars and years to, you know, make a better product. They will probably go with the earlier version of the products, but that's a challenge. So, um, I wasn't expecting that to happen. Uh, that you know that the technology is evolving, it's getting better, it's almost in the best version, but then there are some other things happening around the world and and the regulations. That's a little bit slowing down the market.

Speaker 5: 2:00:39

And another thing was I think right now, at least on the machine manufacturer side, there are so many players with the same claim and for newcomers it's almost impossible to understand the difference between the companies and I think nobody is making the money. And they all have big shouts and big claims. Uh, but it's not like you know, buying a machine and the next day you're printing hip cups with the additive manufacturing. So that's and and design part file management. I think even a very simple thing. We mentioned about the NTOP right. So what NTOP does was really that the difference is on how you manage the file size. With the implicit model you can really make really interesting cases with a lot of details and you can make so many analysis, but still, whatever you have in the end top, exporting it and importing it into the magics, that's still a very big challenge. Sometimes it's not printable what you design. So people are not aware of this, people does not know that anything you design doesn't necessarily you can print it. So there are so many obstacles.

Speaker 5: 2:02:08

We are seeing more improvement in this. You know, integrations between the machines and software and big players and big players. And another thing that I was surprised was I was expecting big players to make more positive impact in the market, like GE or Nikon or maybe some others, orlikon or the others. They came into industry with a big expectation to industry with a big expectation, but then I think it wasn't the response that market was expecting from the big players. I was expecting for some GE to take over the lead and make the machines more accessible, better and everything. Unfortunately, we've been able to see it and I'm a little bit feeling like technology evolved in a level. Now it's the customer. Uh, they'll take the lead and go to the next step. I think there's not much the technology makers can do at this point yeah, I absolutely agree with that.

Speaker 1: 2:03:18

Um and uh. You know, just looking all these orthopedic implant, large public companies bought a startup for 3D printing so they want to bring 3D printing in-house, eroding the revenue for 3D systems, which basically rely on Align for many years now. So that is definitely the trend. 3d printing is not going to go away, but I think, like you said, other industrial leaders are now taking the lead, so you know who is going to be our major. The other huge topic we haven't really touched upon is China. The role China is playing is huge, and I visited China in 2018. It was already pretty advanced, but it's getting there, so anyways. So, craig, I don't want to take it away, but we are running out of time. Why don't you do some conclusion?

Speaker 2: 2:04:24

Yeah, absolutely no. So I think this was really a very effective conversation. I thank all of the panelists and, once again, jenny, for all of your hard work assembling such a great list of speakers. For those of you that are new to 3D Heals, this is not a standalone event. We encourage you to visit their website. As Jenny had plugged earlier, there'll be an in-person event next month focused on bioprinting for health in San Francisco.

Speaker 1: 2:04:49

Not just bioprinting, everything Healthcare printing.

Speaker 2: 2:04:52

Everything is healthcare printing. That's right.

Speaker 6: 2:04:54

Yeah.

Speaker 2: 2:04:55

Definitely sign up for 3D Heals for future events throughout the year and we look forward to meeting those of you that will be at San Diego next month. Let's connect through LinkedIn and other means to continue the conversation.

Speaker 1: 2:05:09

By the way, carl's Met is in San Diego, if you guys want to hit them up.

Speaker 3: 2:05:14

Yes.

Speaker 1: 2:05:17

And they're one of the earliest pitch 3D companies, so kudos to them doing such a great job so far.

Speaker 2: 2:05:22

Absolutely All right. Well, thanks again everyone. Thank you everyone.

Speaker 1: 2:05:25

See you next time. This will be on demand. Bye-bye.

Speaker 2: 2:05:28

Thank you Bye.