BoneChat #132 - Silver Bullet: Disrupting Orthopedics with Antimicrobial Implant Coatings

Okay, welcome to Bone Chat Discussion 132. Uh, today we're joined by Silver Bullet Therapeutics co-founder, CEO Paul Scarrico, uh, to discuss their new low-cost micro galvanic coating technology that is going to disrupt orthopedics. Because it offers a zero-cost clinical upgrade to prevent surgical site infections. I mean, it's— this is brilliant. I'm turning the mic over to Paul, and welcome aboard.

Thank you. Thank you very much. I am just going to go right into, um, right into the, um, presentation.

Got it. Perfect.

Move that back. All right. Everybody can see the slides?

Yes.

I'm Paul Chirico, President, CEO. I'm also one of the founders. I have been in the industry for— oh gosh, now this is my 47th year, 48th year. So I'm starting to add up. Cut my, cut my teeth in, in orthopedics and spine at Eskilapp. So I take a lot of pride in spending time with Eskilapp, and Tiger and I have run across each other. I was the previous founder of a company called SpineAlign Medical. You may remember some of that, and that was a nickel titanium insert that went into the vertebral body to create a kyphoplasty or vertebroplasty type approach. So with that said, I'm taking the approach today. I want to thank Tiger for inviting us to present, but I'm going to take his approach to presenting, and that is a little bit more educational rather than just a self-serving presentation. I really wanted to present it from the perspective of what are— what have been the challenges of going to market and developing a technology such as this You know, there really are— is no competitors out there. I mean, there are certain people dancing around the topic and there have been a lot of talk about it. But, you know, at the end of the day, is there been a commercial competitor or commercial success out there? And there really hasn't been. It's not for lack of need. I mean, this was a report from the CDC and I tried to pick up something fresh. From just January, and you can just see that surgical site infections, or SSIs, as well as hospital-acquired infections account for a tremendous amount of cost to the system overall. And that's not just a cost to the system in financial dollars, but as you can see there, it actually shows that there's a, a huge increase in mortality, and this is even post, post-recovery. So it's almost like when a person is exposed to an infection, hip infections is a good example. There was a study years ago that patients who actually had a hip infection had a mortality rate that was, was greater than patients who were recovering cancer, cancer survivors. So, predisposes you in this area. So this is, this is a significant area that needs a lot of attention. Big costs. Certainly we have the rise of superbugs and that are, that are occurring worldwide. And even if they're as far away as Sri Lanka, they're only a plane trip away. From, from being in the United States. So with a world economy and world travel, as we found with COVID it doesn't take long for something to move quickly. So, uh, there are challenges to developing a technology, an antimicrobial coating specifically, and I'm going to address these. You know, the coating needs to deliver antimicrobial activity immediately. You can't have something that, that builds up over time and then has an antimicrobial effect, or in the, in the world of bacteria, meets the minimal inhibitory concentration to kill the bacteria 5 to 7 days from now. At that time, either the patient's going to be dead or you're going to have a tremendous huge— a huge problem associated with removing hardware and then treating the infection. The other thing is, you know, our company is funded primarily with clinicians. And the one thing that they have told me all the time, don't make it a square dance, Paul. It has to be something that can fit into how medicine is practiced today or surgically is practiced today. So you don't wanna make it something that, It requires sitting in a bowl of saline for 20 minutes to be pre-soaked. And then, then you have to use it within 2 minutes. It has to fit into how surgery is done. The third one is it can't be toxic to mammalian cells. So everybody says, well, you know, when I put a screw in, it's only going to have a certain amount of antimicrobials attached to it. Actually, it's not. You have to start thinking in terms of— and this is what's wonderful about the FDA, is that they're pretty smart people there. So they say, hey, wait a minute, Paul, you can't just say the silver bone screw is going to have this amount of silver. In the case of a bilateral, uh, lateral bilateral ankle fracture, you You may use two plates, two 12-hole plates, which have now 12 3.5mm screws times two, and then two big 4.5mm screws running across the fracture plane. So no longer are you thinking of just the antimicrobial components of just one screw, it's 26 screws. And so You have to start thinking in terms of that. Regulatory clearance is, is critical as well, and I'll talk about that because in today's world, you know, being a 510 means more than a lot of people think, especially when it comes to established reimbursements or DRGs, and it's fitting into the system that was already existing rather than trying to go off and getting it through the regulatory process, and now you have to go through the reimbursement process. And last is, you know, patents are, are, you know, the, the critical, uh, element here of making it fundable, to making sure that you have the capability and the legs to be able to support this, and whoever comes behind you and helps you fund this company can— is protected. So with that said, I also talk about the specific needs clinically. This is what I call my hierarchy of complications. At the lowest level of the— of an infection, you're just going to spend a couple more days in the hospital. You'll take some antibiotics and then you're out., and believe it or not, the cost on that is, is, can, can also be significant. And that just a, just a patient is, that'll cost you another $6,000. But as you move up the hierarchy of complications, as the infection becomes more critical, you know, you end up with malunions with a potential for permanent disability, ultimately an amputation, and and then potentially death. I always tell the story here. I had a friend of mine, 60-year-old soccer friend, soccer buddy. He had been— he has been my friend since first grade, but he was the varsity women's coach at the local high school. And the secret of his success was he ran up and down the field with his players so he could coach them. He was out on a camping trip, tripped on a rock, broke his ankle, and actually when he came back, they put the hardware in, it became infected, and now he has a malunion. And unfortunately, he can no longer run up and down that field. So he had to give up his love of coaching women's soccer because of that. And so it happens all the time. OK, most, most bacteria at the end of the day, they're doubling every 20 to 30 minutes. And we did some tests on this where we actually took silver-plated screws, just silver-plated screws, and put them into, into a medium and expose them to MRSA. And as you can see, that slide down below is where the silver just doesn't release quick enough. The silver ions are what kills the bacteria, just doesn't release quick enough. The bacteria grow right up and over the top of it and behaves just like a control. So you have to develop something that's different. In our case, we have developed a blend of silver and platinum where we have two dissimilar metals. And actually you can see in the lower graph is that at 24 hours we've got a, we've got a not 100% kill, but we've got a kill ratio of, of where we can no longer detect bacteria. And, and we can actually show that on the agar slide above where you can see the agar completely is cleared out by the the silver ions that are now into the— that are releasing into the auger as opposed to a screw with no protection. Again, bacteria grows right up and over the top. And it has to work on a variety of bacteria. This is quite an odd chart and I apologize for it, but what the take-home message here is, these were the superbugs that we tested our product against. E. coli, Pseudomonas. They have to work against gram-negative and gram-positive. And in this case, we had in, and some in some of the slides were the blue, and in some of the slides were actually the, the, the green line. But all of them show that we had a kill ratio that killed all the bacteria at 24 hours. And these were the superbugs. So this was, this was a study that we actually commissioned outside of our, our company. And then we, we actually published this as a press release because we thought it was so important. Here's how our technology works. All we do is we add silver in the presence of platinum, and we do— we've developed— it's take— it would took years to develop the blend where they're in the same plane. And why are they in the same plane? Because traditionally, when they've developed galvanic type systems, you end up having a, a plane of platinum or palladium, and then you put silver or zinc on top of it. But you— what you've done is you've isolated the, the component which causes the silver to corrode off or ionize off. And as you can see here, we've got a release rate for what we call antibacterian, and we release it in 24 hours. So we get a peak at 24 hours and it tails off over time until it's, it's completely covered with new bone or, or it's subtherapeutic and it just releases a very small amount. So you can see we address, um, developing the, um, uh, address killing the bacteria when you need it the most. Most, most technologies are either an antibiotic or they're where they're preloaded with an antibiotic that, that is, that is not resistant to abrasion, especially in orthopedics. It tends to, it tends to be highly toxic to mammalian cells because now you're delivering so much of it because it, it's pretty much gone at 6 or 7 days. So this is, this is what we've developed is a feedback mechanism that looks like a time release, and but basically they're metals. And so this is, this is the secret of our, of our technology.

So I'm no scientist. So what is, what is OH? So you basically emit silver ions and OH. What is that?

Right. So what we do is in the presence of water and oxygen, platinum acts as a catalyst and takes silver and steals an electron away from it, breaks down the water to OH negative. And then spins off a, a silver ion, which is, which is missing an electron. So, and the platinum is untouched because it's a catalyst and it's probably the safest metal in the body that there is. So it's, you know, the body tolerates platinum quite well. So as a result, we deplete the silver ions over time. And around the silver by stealing an ion. And then what happens to the ion? It gets picked up by a white blood cell and then it's disposed of through the liver.

Got it.

And it's got to work against biofilms too, not just active bacteria, but biofilms. This was a report. This was a study that was commissioned by Straumann Dental Implants. And Dr. Zippmann, who is in Switzerland, and they actually compared several different technologies against biofilm. And you can see down below that they've used everything from, um, um, zirconia, zirconium, to titanium, to— there's a whole host of, uh, different, different types of— and I can provide that paper to you. And what they found was the AGPT, our blend, reduces biofilm significantly. And so not only do we kill active bacteria, but we also work on biofilm as well. And this was a peer-reviewed study that was published a few years ago. So now what we have is a technology that works on bacteria, and it works on multiple bacteria, and it works quickly. But again, what I mentioned before is it has to be a technology that fits into the day-to-day current ways of surgical practice. Believe it or not, surgery in Europe is done a little bit different than surgery, or especially orthopedics, in, in the United States. In, in Europe, they tend to go and take out their plates and screws almost within 9 to 10 weeks. In the United States, we tend to leave our plates and screws in for a long period of time and oftentimes permanently. So Our product in this case is approved in Europe. And as you can see, we needed an indication for use that didn't change how you did things. Now, how— what this is, is it basically says if you've had a prior infection or you're a high-risk patient and, you know, patients are high risk, I think all of us now over the age of 45 are considered high-risk patients. Anybody with a comorbidity of smoking or alcohol use is a high-risk patient. So what we have now is a, a, a what we call our OTHOFUSION bone screw system that can be used for open reduction and internal fixation indicated for high-risk patients. That's, that's a major breakthrough for, for certainly the EU. And, and we're still working with the FDA here, and we anticipate that we'll have the same indication here in the United States one day. But it also has to fit, as I mentioned before, the common practice of contouring your bone plates. Then you can see here, We even have marks. You can detect a few of the marks here, right here, where we actually use the pliers to contour, bend the plates at extreme conditions to see if we would have any delamination of the coating or flaking. And as you can see, we don't have any. So this again Orthopedic surgeons are known to not necessarily be the kindest on using their, on their tools and their plates and for, for good reason. And, and we have developed a coating so the coating can't be susceptible to rubbing off or abrasive surfaces or bending or contouring. It has to be durable. And, and so that is a critical element as well. The other thing is it has to fit a lot of product. That's, that's a, that's a big problem. And as you can see here, this is just a listing of the bone screws that we have approved in Europe, and it's in, in the 4,000 to 5,000 pattern range. So it's a lot of product that you actually have to have that kind of fits into everyday need. And you know, there's always that one surgeon that needs that headless 1.8mm screw and you're not going to have it. So we try our best, but the numbers still are pretty big. And again, you can't change the methodology of how surgeons use the product. You have to fit their needs. Fitting their needs in other areas as well. Dental implants. Uh, we have been able to effectively coat both pacemakers and defibrillators with intact electronics where they actually took the pacemakers and defibrillators off the quality line shipped them to us, had us coat them, and then shipped them back to, to the company to do all their water bath testing as well as antimicrobial testing. And as you can see, there's, there's ways of, of coating. Defibrillators are part of the electrical circuit. So you actually, when it discharges, when it charges and sends a charge to the heart,, it actually comes back to the can to complete the circuit. So if you fully coated the can, then you could potentially cause it to, be insulated. So we had to come up with novel ways of striping and still we had great antimicrobial activity and yet we didn't have any effect on the operations of both pacemakers and defibrillators. And we can also coat mesh as well as, like I said, dental implants. So again, fitting the need is critical because again, there are— there is a technology out there for pacemakers and defibrillators which consists of a mesh envelope. Well, when you think about it, not only now they— it adds another $1,000 or $1,500 to the procedure, But the cardiologist has to figure out how to put the mesh, the defibrillator or pacemaker into the mesh bag, make sure the leads are not interfered with, and then tuck it into the pocket that you've just made while the mesh is starting to get mushy. And because it's subjected to fluids of the body. So in this case, you could just slip it right in. Well, now we are on to impurities and byproduct. And again, what this is, is our product, for instance, we, when we coat our product with silver, it is 99.997% pure. The platinum is 99.997% pure. Why? Because there were companies over the last 20 years that were, that were producing silver-coated products that were 97% pure. Well, suddenly what's in that 3% and how much does that add up? And as you can see here, our, our impurities and every product has some type of impurity, is measured in the parts per hundreds of billions. So we are, we are a— and again, you have to sum the number of products you have up. So if you have 24 screws, it's 24 times the impurity, not 1. And, and so that adds the plates, screws, etc. And, and so in this particular case, what the byproducts can be toxic to the body or the tissue surrounding tissue. And this was important. And we ran these studies. There were, you know, a lot of— when you start thinking about the amount of science that goes into developing a coating such as this, It, it goes on for— it takes several years to accumulate this amount of data. And, and it's critical because, like I mentioned before, I have the utmost respect for the FDA because if you don't have it, they're going to find out that you don't have it. And, um, and so you can't hide. This also includes all your biocompatibility testing. You have to do your cytotoxic testing, your irritation sensitivity. Certainly there have been other technologies on the market that claim that they are nanotechnologies, nano silver, nano zinc. Nano just means that where we're operating at the elemental level, a silver element, one, one atom Nano is just a big chunk of something. So it's, it's a larger piece, but it's still at the nano level. Nano is— nano products still are genotoxic. And so rarely do these pass genotoxicity tests. That's critical because as you go through the EU process and as you go through the FDA process, they're well aware of that. So getting a product cleared or approved that is genotoxic is never gonna happen. So again, it's, it's, it's, that is another reason why another more technologies have not been developed in this area because of the limitations of the toxicity. Now, we all know that the best way to, to protect a new implant or, or an orthopedic implant for, for against infection or any other thing is to add new tissue to it rapidly. And so technologies can't inhibit or retard new bone being laid down. And again, this is a study that's going to be published soon. Again, another study, dental implant published by— it'll be fun. It was funded and driven by Straumann. And as you can see here in these lower slides, we actually triggered a rapid tissue increase. So the first question is, why? How did that happen? Again, I'd mentioned before, we're putting two dissimilar metals and we're causing an electronic galvanic system. So we're generating a very, very small current. And what's a small current do? It acts as a tissue stimulator., and we're seeing that result in these slides here and in these electron micrographs, as well as the laser, laser microscopy that was done to show that we had significant new tissue growth onto our, our implants. So again, looking at developing a technology. All these start adding up to why hasn't this market been captured before? Why hasn't another technology been on it? Because there are a lot of challenges to getting a product scientifically that will, that will not only kill bacteria but not kill the patient as well. 510 process. You know, all of us are probably experienced people that know that in today's world, getting a new product that's expensive across the hurdle and into a hospital is going to be pretty oftentimes ignored or pretty limited. And so PMAs and de novos which require, you know, a lot of work. But not only that, it triggers a new classification and oftentimes a new reimbursement. So you fought yourself through the regulatory process. You're now on the market, you're commercial, you're ready to hand it over to your sales organization. And they realize that they have to go hospital system by hospital system and fight for reimbursement. So that slows adoption significantly. 510s then are still a benefit because they have established classifications and you fit under a classification, in our case a bone screw, and we then can fit existing DRG. So as a result, if your product is not extremely expensive, It fits right in and it has established reimbursement. And as a result, so again, a major hurdle, a major challenge to getting on the market. Drug-based products, which, you know, are combination products, which involve, you know, drugs. I don't even know how those reimbursement methods work anymore. So, so, how far, who's the red hole?

Yeah.

Do you go to the PBM? Do you go to the hospital? Who pays for that? And again, and that's another challenge of getting a technology. So the Silver Bullet technology, we are a 510 product and we fit established classifications and reimburse DRGs. So we fit right into the system. And again, we don't force the surgeon to change the way they do things.

That's, that's huge, Paul. So you're, you're basically a 510 with some clinical work.

We're a 510 with some clinical work.

Got it.

Patents. I can't, I can't speak enough about it. When we first started the company, I remember, uh, some of my VC friends would look at me and go, Paul, give me a break. It's silver. It's been around for a couple hundred years. You'll never get a patent. Give me a— no, it'll not happen. Well, it's not just silver. We've developed a silver releasing system. We had developed a system by which we can use sputtering in the same plane and we interlace the silver and platinum together. So when they are exposed to oxygen and fluid or water, in case body saline, they're in the same plane, so they create the galvanic cell and reaction as a result. So we're, we're north of 30 patents now, and I think we have almost the same number in Europe. In fact, at one point in time, several of our investors wanted us to silo the company and create 5 separate companies, an orthopedics company where the IP was supportive of that company, a dental implant company, a surgical company which was surgical masks and sutures, a cardiovascular company. And I'm a, I'm a simpleton. I can't— it boggles my mind just keeping track of everything in one company. Let alone 6 or 7.

So, uh, that's complexity. That's the, that's what Osteocentric went through. They tried to license to every vertical. It's really hard to do.

Yeah.

Um, yeah.

And you know something, uh, Tiger, at the end of the day, when you're licensing it to somebody and they feel that they're missing out, they feel like you're, you're cheating them by, by saying, okay, you can't have cardiovascular.

And just have this little piece right here. Yeah, this piece here.

So it's, it's better to go through the negotiation phase and then find out that it falls out, and then you can take the cardiovascular and move it into something else. So, um, that's my experience.

So the pat—

so you have a, you have a huge patent waterfront and you're not patenting silver implants, you're patenting processes and methods, I, I assume.

That's right, as well as know-how. I mean, yeah, you know, not everything gets captured in patents anymore. There is a certain amount of know-how, and that is critical to— I think know-how is, is in some respects growing as even more important than patents in the future.

So you didn't go trade secret. A lot of people go trade secret if they, you know, don't want to tell the world what they're doing, but Um, there's pros and cons, obviously, but, you know, somebody could try to reverse engineer our product and they were not going to get the same performance. Yeah, no, I get it.

And that's, and that's, uh, that's one of the, uh, that's one of the things that we are, we're proud of as a company. So in summary, uh, when coatings are embedded in polymers or another material, the polymer tends to rely on breaking down or to release the antimicrobial. And this affects the effectiveness, it affects the timing, and it affects the tissue response. So, so if you have something built into zeolite or a polymer that wears down, it's, it's not as predictable in how it's going to break down in my body versus somebody else's body. Or different temperature, or— so in our case, we are exposed to fluid and oxygen, and as a result, the silver ionization that occurs, the feedback mechanism is once the ions get to a certain level, it shuts off, and then when it drops below that, it turns back on. So this is what keeps it kind of as a time release over time. Again, many, most codings relying on like rifampin or minocycline or something else, they, when you're adding up, again, you have to think of the sum of the number of devices that you're putting in, in especially orthopedics. It's not just one mesh area. It's, it's 24 or 36 screws. This can actually increase the toxicity, and it can also increase the, the runout. So, you know, you're trying to adjust for the runout that's occurring in just 7 days. So you increase the amount, and what you're doing is now you're increasing the amount, so it's toxic. Again, most coatings, especially in orthopedics, you know, they have to be handled with kid gloves. I remember reading the, the, the IFU for one company that had developed a silver device, and it said when you remove it from the packaging, use gloves because the coating is so unstable, fragile.

Wow.

And fragile. So, well, I mean, um, and, and you cannot contour it. So like in the case of a plate, you couldn't take it out and you know, take pliers and adjust it for the, for the, the anatomy of the patient that's required. Some drug coatings are drugs or PMAs, and they're just going to be too expensive to adopt long term. We have developed our product where we add basically about 5% to the cost of goods. And in the case of, you take a bone screw, a titanium bone screw as an example. Most 4mm by 10mm length titanium bone screws have a list price of around $350. Now, no hospital and nobody in their right mind pays $350. It's around $100. So, it's the list price versus the actual ASP is about $100. Okay, what do they make the bone screw for? They, they buy them or they make them for around— we get them for around $6 apiece. By the time we coat them and sterilize them and package them, we're at, say, $10. We're still in the 90% profit margin.

Yeah, it's, it's— that's really cheap. And it— that talks about the volume of silver and platinum that you're using. You're using Since it's angstroms thick, you're just barely using any silver or platinum.

That's right, just enough. You— that's the way we describe it. We use just enough.

Yeah.

So in our case, our coatings not only, um, some coatings retard new tissue attachment, new bone growth. In our case, we actually have studies now that show that we actually increase tissue attachment. And there are some new technologies out there that are not coatings at all. So I know of one technology where they have a knee implant, and if it gets biofilm, now you have to put a needle down and touch the implant, and basically it heats the implant up. Well, you've just introduced a new source of bacteria. Because now you've got an invasive procedure going in. You have to evacuate the bacteria off that is now in the synovial fluid. So now you have to remove that because that's a potential source of, I mean, they could form biofilm and then show up somewhere else.

So—

And not to mention it's a second surgery and there's a whole team and an OR needed, yeah.

There you go. And that's, that's an example of something that changes the way we're supposed to do. What we'll ultimately be able to do is work with, and we're not going to have a, we're not going to have a knee. We're not going to develop our own knee. We're not going to develop our own hip or our own shoulders, but we would like to partner off with somebody who already has their knee hip, shoulder, that we can actually show that we can coat all the non-articulating surfaces. You don't want to coat the articulating surface because that's designed to be smooth and it's supposed to articulate a certain way. So you don't want to introduce something like cobalt chromium into this area. You want to be able to go into the area that touches bone. So at some point in time, we would look for a partner in those areas because we're not gonna develop it, just like dental implants. We're not gonna develop our own dental implant, but there are enough big companies out there that will need something like this.

Yeah. Paul, let's turn off the slides and open it up.

Yeah, with that said, I—

Yeah, I'm gonna try to— So who's got the first question? Better bring everybody in.

I want to—

oh, go ahead, Todd, you're up first.

Paul, super interesting stuff, I like it.

Couple questions.

Are you—

you showed a, uh, stainless steel trauma plate. Are you—

do you have material restrictions? Can you coat titanium, um, CP tie? The only Okay, that's— we, when we first developed the company, long-winded answer, we never intended it to be a platform technology. We always thought of it as a technology that would coat orthopedic implants. We never dreamed that we could be able to coat PEEK. We can coat mesh, we can coat stainless steel, titanium. The only, only material that we have not been able to get it to stick to is PTFE. And you know something, we'll give up that one.

Who cares? Yeah, good question. Yeah, I'm kind of interested in the European experience. Can you, can you tell the group what, what was involved in getting the CE mark other than just testing and And then talk about pricing a little bit in Europe, uh, silver bullet screws versus regular screws.

So we're, we're taking a more aggressive approach in Europe, and that is, um, one of the companies we're working with, um, you may know him, um, and we, and we hope that everything moves forward with him. It's a company called Intumed, uh, Adrian Ford, um, We've been talking about the public health system in, in, in the UK as an example, and in the UK, uh, getting new technologies in, especially when, when you have dominant companies that control the tenders there. So, you know, you have a multi-year tender for plates and screws. How are you going to get your product in on the market? Well, We're not just a standard titanium plate and screw company. We're actually antimicrobial. So in this particular case, they can walk in and say, we have an antimicrobial line. And they'll say, well, what's the price? The pricing is going to be— we can price our product at parity to the market without losing and actually gain market share So we're not going to go out there and be the company that says, hey, we have a new mousetrap, we can get 25% bump in the price.

Well, that just takes the price argument right off the table.

We're going to, we're going to throw all of our MBA experience of pricing out the window and we're going to go in and we're going to price at parity because we'll have a, we'll have a reduced margin. But we'll gain market share quicker.

Yeah, I like it. And then tell us about the 120-patient trial in the US. What's— what is it? When did it start? And what are the points?

Well, we haven't started it yet.

Okay.

And the reason for it is we thought we had a partner on that one. And the reason for it is we can— I mean, it's a 120-patient trial. And in some respects, I drag my feet on it because we wanted to start it. It's only ankle fractures. It's lateral ankle fractures.

Open only or open, right? All open. Okay.

So they're all ORIF procedures and they can use anywhere between a 7-hole and a 12-hole plate. So traditionally you would use 3.5mm by 20 to 24mm screws to anchor the plates, and then we'll use 2 screws that go across the fracture plane. That's critical because we've actually hired— oh gosh, what are they— a third-party that will be able to verify on radiology that we have healing. It's really more of a healing study than it is anything else.

Fusion versus some control. Yeah.

Yeah. We want to basically— and it's, you know, most patients, the dilemma here we have is most ankle fracture patients are gone at 6 months. You know, they're pretty much out of the system. They don't want to come back to their doctors.. And so we don't want to have an extreme fallout, even though the FDA wants us to follow them for 9 months. So we're going back and forth right now on how do we, how do we not have a huge fallout and never complete the study where, and it's because the, the, it's the system now more so than anything else.

Um, yep. You know, patient selection's so hard in studies.

So patient selection is going to be critical. We're going to try to— we're going to also include where the study is approved for 10 centers. We'll probably have a blend now where, you know, 4 or 5 years ago, we probably would have gone with 90% hospital-based procedures. Now it's probably gonna be 50% ASC and 50% hospital. And the, and the reason for it is a lot of the patients are done in ambulatory surgical clinics.

Now.

That makes sense. That makes a lot of sense. Are there any, can you tell us about the manufacturing part of it?

I mean, behind the scenes.

Is can you scale, you know, from 1,000 to 10,000 to 100,000 implants?

Yes, we have, we have all the capability of scaling both for, uh, screw manufacturer that we have. Um, we have dealt with two in the past. Uh, one is extremely high quality. Uh, you know, we actually have to— when you perform a 510, you actually pick the number one product on the market and you still have to do the 3 standard tests of pull-out force, 3-point bend, and torque diffusion. So, so if you're doing all 3, so we have to code our product and then go not just do biocompatibility, but we actually have to demonstrate against a predicate, the predicate being a standard, well-known product that's on the market. That has a K number, and we have to be able to— so you can't predicate against yourself, um, and, um, and we actually show that we don't affect the, uh, the torque to failure.

Or that should be easy. That should be easy. You're not changing the dimensions of the, of the screw, so that's, that's kind of a no-brainer. Yeah, those mechanical tests.

But you picked up another one that I've never— didn't mention. Then we do all of our microbial tests using 4mm by 10mm screws. We don't use titanium discs. We actually use the screw itself. And the reason for it is the screw itself has, you know, nooks and crannies and everything else along the, um, um, you know, along the line. So you have to be careful to make sure that again, we're testing apples to apples. And that is how are we— we're not putting a disc or, you know, a 2.5 millimeter, you know, one, you know, 5 millimeter thick titanium disc into the body. We're putting a screw into the body or a plate. The plate's less of a concern, believe it or not, because the plate sits in, sits on the periosteum of the bone. So it sits in soft tissue for the most part. So, so the biggest concern are bone screws because bone screws perforate the cortical, the cortical edge, and they're the ones that contaminate the cancellous or the inner portion of the bone. So bone plate is not the major concern. It's the screw.

Interesting.

All right, Mark's back. Rish, Andrea, anybody have a question before we, we wrap up?

Go ahead, Mark.

So I had to leave earlier and you were talking about plates and screws. Are you doing anything, uh, uh, with total joints? And you probably are, I just missed it.

We've, we have, we've been able to coat total joints, uh, but we have, we're going to be looking for a partner in this area. And that is because we're not, we're not going to develop a total joint. So, you know, you take Zimmer. I mean, Zimmer owns what, 25 to 30% of the, of the hip and knee total joint space. So you take them as an example. It's kind of hard to go off and develop your own or partner with a small company.

Well, I guess really all I meant was you could coat one.

Oh, absolutely.

Okay, that's— that was really what I was talking about.

Yeah, not a problem.

One of the— they can coat anything. They can even coat peek. I mean, they can coat any metals. It's incredible.

Cool.

Rish, am I pronouncing your name right?

Hey, Tiger, uh, it's Rishi, but no worries.

Okay, Rishi. All right, Rishi.

Hey Paul, thanks, thanks for, uh, thanks for the presentation today. Um, just quickly, uh, did you have to test if the coating corrosion affected the strength of the screw at all? Uh, yes, we've done— we actually coated the screws and that's where we had to perform the standard 3 tests of the torque to failure, 3-point bend, and torque to failure, 3-point bend, and pull-out force. Yeah, and we are unaffected.

Okay.

In fact, what we have found is platinum, when it's— when we bond, the way we bond our sputter silver and platinum onto our device, we actually had to do abrasion testing too. Where you send your screw, you know, this is where it's against the wheel and it spins and it looks at it versus titanium by itself. And our platinum actually provides strength over standard titanium in an abrasive, in an abrasion testing.

Interesting.

Yep.

Yeah, this, this stuff's only angstroms thick, but it, it changes. It's amazing how it changes the, you know, it makes it antimicrobial without really changing. Go ahead, Mark.

So Paul, you're, you're probably up on this, but, uh, is there a big difference in surgical site infections between a, uh, freestanding ASC versus say hospital? Inpatient surgery center or hospital main OR? And because I did a brief look, you know, through chat and Claude on those numbers and the cost is horrific.

So the cost, so if you have an infection from an ASC, it's gonna be tremendous, it's gonna be much more costly. Why? Because you can't keep the patient overnight. You're going to have to transfer them to the hospital. And so that's going to drive the cost up significantly. Whereas if you have a patient who's already in the hospital, you know, that's a complication they can deal with there. I haven't seen any data yet that's come out and said that infection rates are higher or lower in ASCs versus hospitals. I would suspect over time that because there's so much variability from one ASC to one, the next ASC, that you will see something related to that. But if there was a study done, oh gosh, about 6 or 7 years ago, and it was published in JAMA, and it showed in neurosurgical procedures, spine procedures, that the longer the procedure, the more contamination from the ambient air. And so at the beginning, they would swab everything that sat on the, on the, you know, the circulating table in the back, and they would swab all that for contamination at the beginning of the procedure. And then if you had something, a procedure that was like 6 hours long, they would swab that, and the contamination rate went from zero, literally zero, to 15 to 20%. So as the procedure becomes longer, so where would I, where would we fit quite well? In a long neurosurgical spine procedure. And one of our co-founders—

Revisions too. Yeah.

A revision procedure. You know, one of our co-founders is Dr. Boden Chopko. Who's, you know, assistant chief at OhioHealth. And he specializes in cranial base neurosurgery as well as complex spine. But when he does these scoliosis redo patients, you know, he gets a nursing shift in the middle of his procedures because he's sitting there for so long. So you can imagine the contamination rate on those type of procedures.

Features.

So, Tiger, one of the guys on the call here is Daniel Schlatter. He's North Peak Surgeon who put a question in the, in the chat. He put a question in the QA, question and answer.

Got it.

Do you see it?

See it?

Yeah. Well, maybe he could put it in a chat.

All right, here we go. I, I, I'm gonna ask Dr. Schlatter's question. Great technology. If O2 and water are required for the metal reaction, What does the partial pressure of O2 need to be, and should a wound be left open briefly to ignite the process? Wow, really, what a great specific question.

That's a great specific question. And that one I don't know.

Well, we'll get you an answer.

I'll check with my, um, my vice president of R&D, Dr. Houdin Denon, who actually is an electrochemist. He did his electrochemist PhD from— and developing—

Houdin's got his hand raised. So we'll— yeah, jump in, Houdin.

Houdin, you're on.

Yes. Can you hear me?

Yes.

Okay.

All the corrosion reaction you see, iron, whatever you see, the principle of the reaction is water and O2 going to OH negative and taking the electron from the metal. Any metal you see corroding, that's the reaction. Amount of the oxygen needed is extremely low. So, if to prevent the corrosion from happening, Basically, you cannot have much of oxygen, and that would damage the tissue, and the problems with lack of oxygen will show up to other things rather than the system not working. In fact, in real human body, that never happens, unless in really, really bad cases that I have never seen. Theoretically, yes, but you cannot have any tissue or any bacteria or whatever grows unless they are anaerobic. That grow in a place that doesn't have any oxygen.

Well, there's the answer. Hopefully that satisfied it, Dr. Slaughter.

Very good.

Thank you, Houdin.

Thank you, Houdin. So we're running— we're kind of hit the top of the hour. Fascinating. I mean, if I were a patient, man, I know what I would want. So we're pulling for you to to get on the market in the US.

Well, I just found out that I may be a patient next— last week that I may need a partial knee and I'm not too excited about it, but I've been thinking, gosh, if I need a partial knee, am I gonna go get one and get it coded so I can get my— I'll be the first knee implant patient.

Cool, do the tibial side and the tibial screws, yeah. For sure. All right, well, thanks, Paul. This has been great. This is, uh, we're pulling for you.

Thank you very much.

Yep, thanks.

I enjoyed it. Thank you again, Tiger.

Thank you. Good luck.