Implant Design and Related Bone Response

As I was reviewing the presentation last night and earlier today, I actually thought it was quite amusing that today I was gonna be telling a story. And, usually, I thought that people scientists usually only tell stories after they’re, like, you know, over eighty five years of age that they have done it all and they have seen it all. And it is quite interesting that about ten years ago, we had only so much information when we were discussing things about osseointegration, especially in this very, you know, different system, which is unique. And as I was discussing yesterday with some people, we are very close to being able to do something which in engineering we call optimization, which means you know, people throw this word, you know, left and right. And when you think about optimization, that means that you know every single variable of the system. You can actually throw mathematical inferences in there, find the maximum, and actually go for it or the minimum. So we are very close to, I think, next year, optimize osseointegration for this particular system, which means we have done so much research on it. We know so many variables, not only from the osseointegration standpoint, but also from the biomechanical components, that we may be able to either improve the system or just let it be as it is. Alright? So the gentleman is the one that’s sitting on the desktop. There’s only one there, I guess. Alright. So the projection isn’t that great because probably because of the lighting. So what I’m gonna do, I’m gonna try my best to actually show you the mainly, the histologic features of, you know, the Bicon system. So implant design and related bone response, people probably think that I’m crazy of even putting that as a title simply because you probably have to have a very solid database to actually be able to dare putting a title like that. Do I know everything? No. Absolutely not. Do I care about knowing everything? I would love to, but I don’t think that in this lifetime I will be able to know a lot about osseointegration. But as I was saying, we have been working so hard over the last fifteen years that we are very close to actually figuring how to maximize osseointegration. So as you can see, there is the et al. Right by my name, and that is because all the wealth of knowledge generated that enabled me to tell you this story, what happens to be this presentation, which is backed up only by our own research and publications. Those are the people that should be really grateful for, simply because they are the ones that do most of the work. These days, I am the CEO of a group. Basically, I just chase after money, and I am the mechanic as well because I place all of the implants when it comes to to the surgery. I work in biomaterials and biomimetics in probably what I call the best dental institution in the world, mainly because I absolutely love the way that school is actually ran by upper administration, not only the upper administration at the dental school, but also at Washington Square. I work also with doctor Loomer, who is actually sitting right there at the Periodontology Department as director for research in that particular department. And I spent you know, I started spending only a month in Abu Dhabi, and now I’m actually up to almost six months teaching at that facility there, simply because it probably is the best university in the world when it comes to the facilities and the student pool that we actually have been able to recruit there. At the engineering school, I haven’t seen anything like that, even after lecturing at Stanford, MIT, and some of the other top engineering schools in the world. So, long overdue, starting this presentation. Osseointegration advances over the last forty years and the mechanisms concerning initial and long term bone implant interaction are still to be determined. We have come a long way. We have worked over fifteen years, as you’re going to see, in preclinical laboratory animal models and trying to match that with clinical research. You know, we know some, but we are still yet to be determining a lot of things. The part that bothers me is that when I was trained in engineering, is that the literature, I could trust the literature. You know? It was built incrementally, one step after another, and that’s nothing like the dental literature, especially when it concerns dental implantology. Our content is not hierarchical. It’s like having a blind library where we have just random volumes. It’s not sequential. All right? And as you know better than I do, it’s highly contradictory. So, you know and that is a problem. If you are trying to do adequate research and development, if you are trying to, you know, move things forward, that makes things very difficult. So we have no informed design platform for implant design. So it is primarily marketing driven. So there are very few companies that I work with, and trust me, I work with all the major ones because they do fund research at NYU, that actually follow an incremental, a stepwise approach when it comes to their own product development. And at times, something just comes about, well, we need something that looks like that because the other company did, and they are selling more than we are because of that. Once in a while, have to test something random like that. What we have in dentistry, in dental implantology, happens to be a blind library, which I call this of size proportional to the investigator’s conflict of interest. I would like to take a side note here, is that I take money from everybody. Therefore, I have no conflict of interest. If you take money from only one, you’re in trouble. Two, maybe. Three, I take money from more than twenty. The good thing is when you have such a large program, and I’m not by no means I’m saying it is the best program in the world when it comes to research, is that if one goes away, you’re okay. The power in any relationship lies upon the side who cares less. If a company comes to me, Well, want you to do this, and I’m like, I don’t want to do it. Well, then we walk. I’m okay. I will only publish what I think is right and what the data is telling me, not what the company wants me to publish. If you don’t believe in anything that is being shown here, you are more than welcome to go to New York, very nice lab, the heart of Manhattan, and you are welcome to actually read everything else and perhaps we will come up with something you know, not too different than what has been generated in the lab. So more than welcome. You know, it’s an open book. So, you know, going back on track, so progress has been slow relative to other areas. Dental implantology, we have been around for forty years, and what I’m about to show you goes against what has been said for forty years. So it’s going to take a little while for me to tell you this story, but always based on solid data from preclinical animal models and clinical studies as well. Okay. So design, needless to say, it is an ambitious topic. So we start with macrogeometry, then we go to microgeometry, the surface treatments as well. The word that has been bothering me a lot, especially as I owe Tomas Albrektsson and Anne Winterberg a chapter for their book in nano features for osseointegration, which I have not even put together the title, I should get started on that this weekend. So and then we have surgical instrumentation. Where have we concentrated over the last number of years as far as you can remember? Right here. Guys, and I’m going to prove to you by a plus b equals to whatever that this is useless unless you know this one and this one and their relationship. Okay? This is an ad hoc. The most important component of osseointegration, short and long term, happens to be macrogeometry and surgical instrumentation. How many articles have you read about surgical instrumentation of dental implants? It’s a joke. I mean, you look at the literature, it’s, you know, ten papers that probably we wrote and a bunch of book chapters that have no foundation no scientific or experimental foundation whatsoever. Okay? If you understand the relationship between macrogeometry and surgical instrumentation, you may have a chance of making the best surface in the world actually useful. There are many surfaces out there that are outstanding when you put them in healing chambers. If you put them on a screw, they’re very much useless or very close to useless, especially in regions where you’re going to screw very tight and very dense bone. Alright? So we’ll get to that later as well. So the ideal implant, of course, will have a macrogeometry, a microgeometry, a nanogeometry eventually, and a surgical instrumentation. But what people fail to understand is that the physical part of it on macrogeometry is not only bulk integrity, surface area, you know, exposed area or something like that. It does have a big role on bone biology, short and long term. Alright? From the biological perspective, you have the fast healings and you can have actually bone evolution to cortical like high mechanical properties configuration over time. We published extensively on this. We have proof not only from histological sections, but also nano mechanical testing of this bone that depending on your implant, bone will evolve towards a cortical like configuration, and the mechanical properties of that bone will be the same as or comparable to Haversian bone cortical bone. Well, but you’re pulling it from, you know, the anterior region of the mandible. No. Posterior maxilla. Grafted regions. You know, we have as many sections as you’d like. Actually, in fact, over 300 and 210 that we would just use to write a paper on it. Microgeometry, yes, it is important so long as you figure out your macrogeometry and surgical instrumentation. One of the fun things that we’re figuring out these days is that no matter how you instrument, the slower you are, and the lesser the number of iterations you have to go to your final diameter, the better off you are. I don’t think that that’s a big surprise for many of you in this room, but go elsewhere and tell them that. I remember giving a talk, where was this, in France not too long ago and they didn’t like that one bit. They liked to use the nine drills to go from the pilot all the way to whatever countersink they use because it is going to give them the best primary stability. I looked at them and was like, you got it all wrong. Just backwards in the end of the day. Anyway, let’s move into the very first feature, macrogeometry. As you all know, if you go to different designs that you have there, all the companies claim that they have the best microgeometry, the best surface, with the best this, that, the other. Peri implantitis doesn’t exist on their surfaces. Especially as you analyze. I mean, talking to Peter, he knows that no matter what macrogeometry or what surface you do get infected implants. So it’s kind of funny how actually companies present their product and especially on the longer term, having done some research on the short term. So anyways, people do tend to believe that osseointegration takes place exactly the same way regardless of implant system, and then we prove them wrong. And they accepted it. And that’s pretty cool. Not only our group, but also group in Sweden and a couple other guys in Italy. You know, now we know that they don’t heal through the same mechanism. But then somebody raised their hand and said, No, but long term they are all the same. And now we are in the process of showing, again proving that they don’t. And depending on primarily how they heal, they are going to look very different long term. That is something that we will be discussing as well. Run down on a very quick study. It turned out to be a classic one, and I just refused to take their micrograbs, which are not that great, out of the presentation, because I have other ones that are better along with it. Six dogs, two times in vivo between four weeks. Proximal tibia simply because they didn’t want to deal with the problems that we have in the mouth. Were just looking at osseointegration. Three macro structures with distinct surgical protocols. We did histomorphology, histomorphometry. You know, pretty simple design. Very, very simple. But this is probably one of the most important slides of the presentation, and if not the most important one. So if you look at the dash line, that’s the outer diameter of the instrumentation that we had. Alright? So what happens to the short pitch implant? It goes in super tight. Right? You got that phenomenal primary stability, which has been regarded as something very important for us integration. And you’re gonna see that that’s exactly the opposite. Alright? So then we have something that is the large pitch implant, where you have, you know, a larger thread pitch, and you do have some engagement between bone and the outer part of the thread. So what happens is that you have primary stability that is going to be related to the carpentry design of your thread. Right? There’s no rocket science on it. You know, even though some people claim that there’s something very important about it and something very specific. No. This is pure carpentry. Alright? And you end up having a healing chamber right there. Okay? Leads to something that I call hybrid healing, which is pretty cool, but it’ll be a while before people figure out how to make a atemporarily stable implant based on this. Alright? And then there’s the plateau where the, you know, the Bicon-like implant, experimental implant that we used at that time, and it leads to a very large healing chamber. You have minimal primary stability, basically, due to the, you know, fact that you instrumented the bone very much at the diameter of the implant. Keep in mind, one goes in super tight, the other one goes in tight, but it allows for some space here for a healing chamber, and so does the Bicon as well, a very large healing chamber right there. Now I’m not very proud of this histo, but I don’t take it out for a variety of reasons, simply because when you look at the two weeks to four weeks here in this short pitch implant that went in very tight, What are we seeing? At two weeks, and we cannot see, not even there, due to the projection, but that bone is not really forming. That bone is going away. And I’ll show you a lot of slides that will better characterize this at all. So what you’re having, you’re having a catalysis, a catabolic phase of osseointegration. Basically, it’s deintegration because you have, as you place the implant, almost one hundred percent bone to implant contact, then it remodels away because of the pressure that you put on bone before actually bone grows back from the old wall towards the implant surface. Alright? So let’s think about this for a little bit. How how effective can be a surface treatment if basically you’re putting a bunch of you know, you you’re basically doing osteoclastogenesis here, which is going to remove that bone away, and the osteoblast will have to travel at two to four micrometers a day, two dimensionally, literally, towards the implant surface. It doesn’t make a whole lot of sense. Right? The osteoblast is not gonna get to see the treated surface because basically you destroyed it when you’re putting it in. Beagle dogs are pretty awesome. They heal, for example, there was a clean up here between two and four weeks, and then you have the integration here through something that is called the appositional bone healing, two to four micrometers a day. Now, if you think about it, if you have a dieback of one hundred micrometers, which is a very small one, you know, just as an example, it will take a while before that gap is closed. And with that said, you are going to have a decrease in your biomechanical competence on the system. You may have micromovement and that may result, as you well know, in integration. Right? Now, looking at this implant here, which had primary engagement with bone in a healing chamber, it was pretty remarkable how well filled this already was at two weeks and it just evolved from two to four weeks. And this one, the ones that work with Bicon knows that you get very rapid bone formation and then from two to four weeks, you’re just gonna increase in bone maturity. Right? So moving forward, not the prettiest actually, these are very pretty. It just it’s difficult at times to explain what’s going on here. So once you take a microscope, you polarize the light, you can only see how the the directionality of bone here. And the person who actually made this micrographs turned out to be someone who is a Planck laureate, which is like for anthropology, which is like the Nobel Prize for anthropology who works in my department. And every time I need to be humiliated by someone, I sit down with that guy on the microscope because he’s a bone morphologist. And then I just realized how much I don’t know about bone. But, anyways, we’re looking at the short pitch implant here, the large pitch implant here. We can see, actually, the instrumentation one through there. Alright. And the plateau implant right there. But the one I want you to pay attention to is this guy right there. Okay? If you can see, there is a very fine white dashed line right there, and that’s obviously artificially up placed in there because you see a very different pattern when it comes to the old bone here, which light goes through very well, and the bone that was actually formed after, you know, the whole interface remodeled. Okay? The micrometer bar there shows me that this distance happens to be two hundred and fifty micrometers. It’s basically a quarter millimeter in both sides of the implant. Alright? If you load that, you know what’s gonna happen. It’s half millimeter room for the implant to wiggle in there. So not only that, know, in humans, the cleanup happens to be pretty fast. It takes probably seven to fourteen weeks to fourteen days. Alright? But then remember, our osteoblast happens to be much lazier than any other species. Okay? The velocity that the osteoblast is going to come from the old wall towards the implant surface is two to five two to four, five micrometers a day. Two hundred and fifty micrometers, two hundred and fifty divided by five, that’s the number of days that you need to close that gap. Alright? And that’s not a short period of time. Now, in the other one, in the other case, where you had primary stability due to carpentry and interplay between your instrumentation, you already have this bone here, which is sort of diffuse in polarized light, which is woven bone formation right there. Okay? You can see the instrumentation line right there. And in this guy here at four weeks, large healing chamber, what you see here is primarily woven bone and a little bit of lamellar bone already. So very, very different ways of healing, and I am going to, you know, just show a couple more how do I go back? Here. Examples of that so we really get you, you know, understand that one. The good part of it is that if you think about the healing chamber, bone grows of course, you have much larger spaces to fill, but bone grows at thirty to fifty micrometers a day. It’s like a bone callous. It’s like a fracture. When you have the tight fit, first bone has to go away and then you have a much slower bone growth to fill that gap. Also, this one takes place very much three dimensionally because it goes from the surface into the healing chamber, within the healing chamber, and from the instrumentation line towards the healing chamber. So this is going to close a little faster than this simply because it’s growing in every other direction that you can think of. You don’t have to remove bone before bone is actually occupying that region. You know, bone is you know, there’s apposition there. And, you know, it just it is a different dynamics. Alright? And the mechanical properties of that bone is going to evolve far differently than in this scenario here as we’re gonna see later. Now typical typical typical micrographs that you would see in a brand of archetype implants and MK three threads. This is another study from the group. And I joined me a couple of years ago, three years ago already. What we see at two weeks is the typical histology that you would see in many, many studies. They’re very proud of it because the bone to implant contact happens to be, I mean it’s a hundred percent and that’s a beginning of remodeling of that interface. And why is that? Because your instrumentation actually passed right into the, you know, near the inner diameter of the implant. What else am I seeing here? This is cracked bone. Alright, guys? What happens in bone cracks? You disrupt the osteocyte network and that results in osteoclastogenesis. And this is the panorama that you get later. Alright? Just recall that everything that’s blue here between two and four weeks in a beagle dog happened to be empty space. How good of a design is this if you’re actually loading it from top to bottom? You know, it doesn’t make a whole lot of sense to me. So I’m almost to the point that I’m going to start claiming that we have been doing, you know, something to bone before osseointegration, which is, you know, let’s deintegrate the implant because it starts with very intimate contact between bone and implant and then we kill the hell out of it and then bone slowly grows back towards the implant surface. So that’s not really what we would like to have simply because you would have a stability dip, which would give you chances for a bunch of different things including, you know, the integration, potential infection, you know, and the list goes on and on. Now another example just actually, this will come out of iGeoms probably a couple weeks from now. Another implant that went in super tight. Alright? What are we observing here? Especially at the thread tips where the highest stress concentration happens to be. Guys, these are not osteoblasts. These happen to be osteoclasts. Right there. There, there, there. Simply because, look at the amount of micro cracking that we got, because you were searching for that immediate stability that gives you a nice reading on some toy that is out there that provides you with a number. What happened here between the treads? That is the region where you are going to get a lot of stress as well. That’s bone remodeling right there. Bone is going away. Alright? It does come back eventually, as I have said, but look at that. The area where you have cracks and you have high stress concentration, you don’t have osteoblasts. You have osteoclasts. If you label this for osteoclasts, that’s all you’re gonna get here. See, the osteoblasts make very nice lines close to where bone opposition is taking place. Okay? Whereas that guy, that’s just taken bone away. So, tied it in. It’ll be the standard of care for many different professionals and systems, but that’s what you’re gonna get. If you have time to wait, you can do that. That’s not a problem at all. They will ultimately integrate. Now what happens then is what is important. Okay? Now after we published a bunch of this and I went around the world lecturing on the different bone healing mechanisms, some companies decided to come up with the hybrid healing, which does make sense from a variety of standpoints. Alright? So what’s going on here? This is an instrumentation that goes, you know, allowing for a healing chamber. So what you’re seeing here is, you know, the standard healing chamber healing, and you do get some primary stability. Okay. But what is the biggest problem with this? Alright? Is that where you have engagement between implant and bone, and that is going to result in high stress levels, that’s remodeling right there. I’m not even getting into solid mechanics and the mathematics of it, but this is bad. This is almost as bad as tight fit implants right there. Because from a biomechanical standpoint, it is going to lose mechanical stability very quickly. Okay? Can we make the hybrid healing better? Yes, we can, but it is going to require an extensive database that will not be generated in less than five to ten years to actually optimize or improve the circumstances of this engagement right here. Will the implants start looking like that? Yes, you’re going to see a lot of that over the next five years. Over the next ten years, I would say ninety percent of them will look like this. You just can’t go against what’s being published these days. With due respect to people that have been publishing on this for a number of years before our group started to do this work, it was there. It’s just that they were not seeing it. Because they were taking for granted that you had to remodel the whole interface before you actually achieved osseointegration. There are different approaches that it’s pretty obvious by the number of studies that we have done so. Red arrows depict problem, depict, you know, bone being taken away. And that’s not really what you want when you’re trying to achieve osseointegration. Okay? Now, finally moving into the healing chambers, This was one of the most fun studies that we ever conducted that was done in Dublin to begin with. Was awesome, getting to work there. Know, eight Beagle dogs, extraction followed by eight weeks healing. Implants were placed remaining for three, five, eight, and twelve weeks in vivo. And the two systems that we had, this one is experimental implant full of healing chambers, and this was just a Straumann regular implant that goes in tight fit. This was published back in two thousand and nine. It’s a highly cited paper. It’s one of my favorites, even though I think that we’re doing a far better job when it comes to the post mortem part of the study, the laboratory component. We got much better at it. But nonetheless, Gary did a phenomenal job on this. Just for you to see what the panorama happens to be in a healing chamber implant as it is placed. Okay? This is already at three weeks, so there’s some bone form between the the the within the healing chambers. And three weeks after, you have, you know, a tight fit implant. So this is bone to implant contact at a hundred percent, and that one basically starts at very close to zero. Alright? And, you know, people would say, well, this is a worse scenario than this one happens to be. And this study shows us exactly the opposite. So what we’re seeing at three weeks at the healing chamber upwards and the tight fit downwards, I mean, you can tell me already what’s going on there. Alright? You’re getting bone formation within the healing chamber from the instrumentation line towards the center of the healing chamber and from the surface into the healing chamber. Alright? What are we seeing here? You know this better already. I showed plenty of these already. This implant is gaining stability, whereas this one, you know, that interface is going away. Alright? So that goes to show. I mean, you may start with a hundred percent bone implant contact, but how much contact are you going to get and for how much time, for how long that is going to be there to assure biomechanical competence of the system? Alright? So very interesting to see. Now from three weeks to five weeks, of course, beagle dog is phenomenal. So it healed. You had appositional bone closure here. So it is fully osseointegrated, as you can see. And at five weeks, you the healing chamber is pretty much filled. It doesn’t fill much more than sixty percent these days, even though we try to fill it more. It’s just physiologically impossible, and that’s actually a blessing when it comes to the content that you get there, which is very rich in blood vessels and cell content. That results in something down the road that is very important. Now let’s look at this interface down here and the one up there. Remarkable differences. One looks like a cement line. That means for you to remodel that and increase the biomechanical performance following Wolff’s Law in this panorama is much more difficult than in this one here. Why would that be? Simply because you have the appropriate amount of vasculature and cell content there to remodel very fast and adjust and adapt the bone to the biomechanical loading that you’re going to suffer. This one, whole cellular pathway to remodel that particular interface is different than longer. Right? And then, as you go from eight to twelve weeks, the osteons are already the primary osteons are already remodeling, you know, extensively, whereas this one, there’s not much happening at the interface. So people are like asking, Well, one heals differently than the other. Fine. One results in different cell content early at early times in vivo relative to the other. Well, but they’re both osseointegrated. Alright? And then I look at it, so let’s see what happens down the road. You know? How will this interface here, this bone full of osteonic structures, will behave over time relative to that? But before we get to that, you know, let’s look at a couple of other studies that we have done because the healing chamber is pretty awesome, but, you know, there are limitations both in their, you know, small size and in the large size and on their shape as well. So something for us to be looking at, and this is something we have done a number of years ago. Also, one of my favorite papers published, I think it was, like, two thousand ten, two thousand eleven, where this company actually gained information regarding the healing kinetics of different healing chamber sizes. And that’s why you notice a difference in design from two thousand and ten, two thousand eleven to now. Because some of the short implants already incorporate some of the features of those healing chambers. And we thought we learned some out of it, but in reality, we’re running another study with nine different healing chambers of different heights and depths in hopes to actually draw that line where we were gonna be able to find the maximization point of bone healing. Okay? So, you know, there’s more coming soon. As I said, I think a year from now, I’m gonna be able to make an intelligible decision along with Fred Weekly as to what the size of this guy should be for maximum bone healing and maximum biomechanical competence. So this is gonna be pretty cool. You know, that’s one of those things that you do sequentially, at least it, you know, leads into something that can be potentially much better than what we had in the past. Okay. So just going, you know, the rundown of healing chambers. At three weeks in vivo, you primarily get woven bone from the surface and within the healing chamber and growing from the surgical instrumentation line towards the healing chamber. And then people go, oh, well, but you’re getting woven bone formation in there, and those have very low mechanical properties. You know what the problem is? Is that people never tested woven bone appropriately. Now that we have the nano indenter available and we can actually go very you know, if I want to go here and measure the properties of this bone, I can go. And it turns out the woven bone doesn’t have such low properties compared to cortical bone. What kills woven bone is, you know, how much space you get between it. Alright? Between their features or the the the morphology. But it has very remarkable properties. So the more bone we can actually put in there happens to be that we’re not gonna be much worse off than if it was a Haversian cortical bone like mechanical property. Okay? But what’s really interesting about this? Well, woven bone is woven bone. And if you don’t like woven bone, you know, a couple weeks later I’m gonna pass this because this is something that I will address later as well. You already have lobular bone there. Okay? And every single one, every single feature that you’re seeing here happens to be a primary ostium. So what’s in the center of a primary ostium? That’s a blood vessel in there. And the blood vessel is the one who is going to be carrying the process of remodeling along with osteoclasts by following it and remodeling. Okay? I think everyone knows bone physiology to understand that that’s gonna be the case here. So go from woven bone that forms very fast towards lamellar bone with primary osteons. And what can happen here? The only thing that can happen here is that you are going to have a very high remodeling potential. Okay? So this primary osteonic structures, there’s a rapid development of these bone mechanical properties there because it does have the high vascular cellular content for modeling and remodeling potential. Now if you remember the other scenario where you tight fit an implant in, bone dies and it grows back, no blood vessel, very little cellular content. Does that have the same potential to evolve mechanical mechanically and bone wise physiologically or, you know, under mechanical stress? Of course not. It’s a different animal. Alright? So let’s move forward towards what happens to these guys at long term. Alright? A couple publications. Actually, there are four out there these days. This needs to be updated. But this is the most remarkable feature of healing chambers, how they actually evolve over time. Again, guys, not really seminal work, but this is the first time that this was shown in the literature. Not my theory. This was Jack Lemons’ theory back, I don’t know, when I was in graduate school there a long time ago. And, you know, we pulled the implants out, not we, but the guys at Bicon, and they send us this type of things for us to look at. And you now this you know, sometimes I show a histology that is not that pretty, but that’s because back then, we didn’t know how to make them better. As you’re gonna see later, it evolved a lot. But this one was done like this on purpose. Alright? Because the point that we wanted to prove was that the healing chamber implants, because they have woven bone which evolves to, you know, primary osteonic structures, and if you put them under loading like this human retrievals were, and, you know, this is a ten year human retrieval, those primary osteons would actually merge forming a Havers and Volkmann like canal. And if you have a version system, the likelihood that you’re gonna get higher mechanical properties happens to be much higher. That’s basic. Alright? And indeed, we did. Alright? This is actually very cool. So in this type of microstructure is directly related to the surgical instrumentation and your microgeometry design as, you know, a replacement implant. It starts right there. Time equals to zero. It’s not, you know, something that develops because the patient, you know, chews very hard. This is something that there is a reason to begin with. Alright? Now we did that not only with the regular titanium surface, also with the HA implant surface simply because doctor Morgan wanted us to do so because people were bashing AJ for whatever reason, and we haven’t found any problems with any of the human retrieved bicon in there. Eight months after placement, two months after loading, so you still have woven bone there. You have the lamellar, which is not projecting well, here’s an osteon, another primary osteon there. Humans are a little slower than beagle dogs, but you know ultimately we catch up. And then if you look at something that is twelve months after placement, six months after loading, you already have a very large osteonic structure there, and a couple more forming down here. Alright? Three years after loading, osteonic structures there, Haversian Volkmann canals within the system. And the interesting part is, Paolo, were all of these pulled out of the anterior mandible? No. They’re from all over the place. Alright? So even if you don’t believe it, you know, just come to New York. I’ll present you the slides and the patient charts. We have it all over there. Alright? As time elapses in vivo, it gets even more interesting because those primary osteons, they tend to merge into a larger osteonic structure. Very, very high mechanical properties here. At that time, not measured, but now we do have the numbers in there. And thirteen years in function, I mean, this is not unusual. This is artifact from from the processing, but the number of remodeling cycles that we have there is quite remarkable. I have better slides later on the presentation as well. So that’s what happens. It starts at time equals zero. Implant placement. Okay? So something for you to think about. Now twenty four years in function, that’s what you get. And if you run a measurement of these large structures, they happen to be exactly the same or very similar to the size of the osteonic structures in Haversian and Volkmann canals in you know, long bones. So something very interesting for you to think about. Now even though we had you know, there’s always that question, well, it looks like cortical bone. Is it? And then we addressed this question through nanomechanical testing. And the interesting part is that we had we had implants that up to five years in vivo, they didn’t have quite high mechanical properties. But after five years in vivo, it just jumps up because of the remodeling. Right? Wolf’s Law. So, basically, after five years in vivo, you have bone that has mechanical the mechanical properties of cortical bone in the posterior maxilla, in the post in the posterior mandible, even in grafted regions. Alright? Statistically, you’re gonna see later that nothing matter matters around this implants but time when it comes to the long term osseointegration. Alright? So from a microgeometry, plateau healing chambers, well, we know that the microgeometry plays plays a big role. You got woven bone, then it goes towards this lamellar bone that has primary osteonic structures on it. Right? Then from this primary osteonic structures, then you move towards this thing right here, which is this cortical like morphology bone with very high mechanical properties. And that’s all nice and good. This is pretty cool. But, you know, people, in the end of the day, they’re like, well, but you do not necessarily have primary stability. How can you boost osseointegration to a system like this? And I already alluded to it, but we can cover this rather extensively. Alright? And that would be simply because the only situation where you can fully benefit from a surface happens to be when you have a healing chamber. Why? You have that healing chamber, blood clot goes in. What happens then? Alright? Fiber network forms. If your surface is good enough, it’ll keep that fibrin network right there really close to the implant surface so the cell so the cells can actually travel to the implant surface, we’re as we’re seeing here, and actually start forming bone from the implant surface backwards. So that’s one of the strategies that we have. Healing chambers facilitate the efficiency and effectiveness of surface treatment to Hasten osseointegration. Okay? And then we go back to the second. We go on exactly to the second design feature that I’d like to address, which is a surface. Probably, yes. I would say we have the largest research database available. I wouldn’t say that it’s the best, but definitely, if you ask me, you know, have you tested this, that, the other? I said, yes. And can you relate one to the other? Yes, can do that. I don’t do that very often, but, you know, off the record, I do that more than, you know, when I’m on stage simply because it’s, at times, undue. But once again, all the manufacturers say that they have the best surface with the highest surface area. They’re all nano these days. They just buy a very powerful microscope and they find nano features on it. No peri implantitis. That doesn’t exist. Even some people on the podium are saying that, which is, I would say, quite entertaining. Two key review papers that have been highly cited as well, one by my group in New York, and the the other one I tagged along with Tom Albertsons group in in Sweden a couple years ago. We have thirty plus manuscripts on in vivo surface evaluation, so it is a large database, pretty consistent when it comes to the model and times in vivo. So we have an idea when we’re comparing one material to the other, even though they haven’t been tested within the same subject, which is very important in in vivo research. And the question is, what have we learned after all this animal research? We have learned a lot. And that nothing beats something called the Integra CP surface, and I’m not here to make you know, any advertisement of it. It’s just the fact. Okay? Put a calcium phosphate surface on any implant design. It does have synostrointegration. Plain and simple. Okay? It can be boosted. Of course, we can do better than that. And that’s something that Vin was showing earlier today. And, you know, if you look at this, this plume basically is at thirty seven degrees Celsius. As you’re gonna see here, you end up getting a substantial amount of hydrophilicity to the surface, plus you can tag things to it from a chemical perspective. Now before even moving forward, guys, is this important on a healing chamber? This is very important because it allows you to have very intimate contact between your blood, which is a blood clot, and then turns into the fiber network, which will become osteogenic stroma where the cells can actually differentiate and migrate through that network. We’ll see that later as well. Now this is something this technology will turn any surface into something much better than it was before treatment. It doesn’t matter whether it’s machined, it’s calcium phosphate, or just, you know, the the typical texture titanium surface. But remember, if you go with an implant system that goes in tight, doing this and doing nothing is very close to nothing. Alright? Now and this is something that I can say publicly because I was in Basel not too long ago giving a talk to the upper management of Straumann, and I said the SLA active surface is outstanding. The way they tested it was beautifully. They put them put that surface on healing chambers, and they put that on Journal of Dental Research two thousand and four. Alright? Now it is a great surface, but not necessarily for their system. I’m not saying that it’s not good for their system because it is, but it’s it could be far better, you know, used or useful if the implant was differently designed because that’s a tight fit implant. Alright? That’s no secret. I’ve said that. I spoke to them and and believe me, they understood it. So I think that they’re eventually going to change at least the instrumentation or, you know, something’s going to happen and, you know, they they work hard and in a stepwise fashion as well. So I expect something nice to happen out of that too. Okay? So let’s look at the titanium treated textured surfaces. And this is too bad because it’s not projecting as it should. Okay? So you’re gonna have to take my word for this, or I’m gonna actually pull this TV and turn around. So what’s happening here, this is at one week. K. This is the non plasma treatment, and this is the plasma treated surface. And what we observe in this case is that the fibrin network, the blood clot, did what it was supposed to do. Alright? What does a blood clot do? It contracts. Right? And if you don’t have the surface atomically clean like you do after you treat things with plasma, it will contract away. And that’s not too bad, but, you know, there will be a distance which the osteoblasts are not gonna be able to travel. Okay? So then you’re gonna have to form bone within that network, and then bone will have to oppositionally form towards the implant surface. Alright? Now if you look at this guy here, that’s the plasma treated one. The fiber network is in intimate contact. Okay? Or the osteogenic tissue, at this stage, is already osteogenic tissue. It’s in intimate contact with the implant surface so the the cells can freely travel there. You already have bone formation right there. I’m very sorry it’s not projecting the way it should. Then when you go from one week to three weeks, yes, there is bone formation there, but far less in contact with the implant surface than it would be in this scenario. And, you know, three hundred percent increase in three weeks. You know? We’re used to hearing, well, we got twenty, twenty five percent increase. No. This is three hundred percent increase. I don’t think that I can get NIH funding to pursue this further because they’re gonna say, well, you know, it’s already three hundred percent. You know, usually, we go after twenty percent, and that’s good enough. Now this is for the textured titanium surface. Okay? How about the highly osseoconductive Integra-CP, you know, plasma sprayed calcium phosphate surface? Vin, you were wrong. Where is he? He’s there. He said only twenty percent. No. That is not twenty percent. That’s one hundred and twenty percent that you get. So you can further boost osseointegration of calcium phosphate surfaces as well. This is a good, much better example than in the previous slide. As you can see, non plasma treated, you get the contraction of the blood clot leading to an osteogenic tissue that doesn’t seamlessly link old bone to the implant surface, whereas this gap is nothing but artifact. You get a much more intimate interaction between the osteogenic tissue, implant surface, previous bone, and old bone. What are we seeing there? That’s already a blood vessel forming. So that is going to be likely the very first primary ostium of this whole structure. Okay? We’ve we’ve done also biomolecular tagging. We did DMP two on the implants as well. Different model, ship hip model. There’s a good thing about this one is that it’s so large that you can put as many groups as you want, and you’ll get the best statistics out of your study. Alright? The only problem with it is that it’s large, and then handling the animal before and after the surgery is a little more involving. Let’s put it this way. But if you tag biomolecules that will result in different cellular behavior as soon as the cells get to the implant surface, it increases over a hundred percent osseointegration of the titanium surface and fifty percent of the calcium phosphate surface. So the calcium phosphate surface is already to start with a great surface. There’s only so much you can tag to it. Now between you know, that’s that’s where things start to become more interesting. If you look just at the naked titanium with no tagging, compared to the calcium phosphate surface with biomolecular tagging, you get six hundred percent. How fast are we going to be able to do this? I think even faster in the near future. Okay? Now moving towards the last one that I would like to address before we wrap this up. Okay? Drilling technique. Very little in the literature. Literature. Alright? All we know is what is in books, and they say that, you know, higher speed is better because you have better control of your hands. And what else? They say a lot of irrigation. Right? And then we go exactly the other route. We do things exactly the way they they told us not to do. So fifty RPM, no irrigation versus nine nine hundred RPM with irrigation. It turns out that fifty RPM was more favorable than, know, the high speed drilling. Was I surprised? Yeah. According to literature, I should be surprised. Alright? And more importantly is that as you injure bone, what’s gonna happen? Bone will die back regardless. It doesn’t like being cut. Right? And if you do lower speed drilling, the amount of die back that you get is smaller than if you do high speed drilling with irrigation. Okay? So if we’re trying to do like, you know, Maserati or Porsche does, which is incrementally increase incrementally increase the efficiency of osseointegration, this is meaningful. Okay? Because we’re working with many different variables, healing chamber size, healing chamber design, molecular tagging, you know, surface treatment, and surgical instrumentation is very important. Alright? And that leads into the next study that we have ran, which we had one hundred, five hundred, and a thousand RPMs on osseointegration. Alright. And of course, we did all the stats and those lower the battery and yada yada, all with irrigation. Think that if we did without irrigation, the lower speeds, we would even be better off. And that journal, I love this journal, and they asked us to put a clinical relevance of this. And then we looked at the literature, there was no literature. It’s always difficult to publish something on surgical drilling because they always ask you for more literature, and there really isn’t much out there. And I’m not gonna insult your intelligence by reading this to you, but that’s what the corresponding author came up with. Ladies and gentlemen, we’re dealing with bone. The instrumentation is not important, what is? We have ran multiple studies for a variety of different companies, not only dental and orthopedic, and the effect of surgical drilling is so drastic that you would be amazed. But that’s you know, this is ridiculous. You know? Thus, understanding the biologic effect is clinically beneficial in selecting the proper drilling sequence and velocity, whatever that is. That should be implicit, but they wanted us to make it explicit. Moving forward. Couple things we know. Long term, it’s all about the interplay between microgeometry and surgical instrumentation. And I have just shown you that the short term surface treatments and biological factor additions are ad hocs to the long term guy. To the microgeometry plus surgical instrumentation. What is the final proof of what I’m saying when it comes to the long term? And this is something that we just submitted about a month ago to Journal of Dental Research because number one, nobody has the cohort of samples that we were able to put together. And number two, nobody knows the fate of osseointegration over time. You know, they always pull one core here, another core there. They make four hundred papers in the literature, but doing something like we have done this time is very unusual. So study design turned out to be human retrieved samples. Men, women, children, you know, I don’t know what the statistics of that is because it was not important. Once we ran the numbers, it was not important. They were all obtained due to prosthetic retreatment. The important part of this is that they were all placed in the same clinic, under the same surgical and prosthetic timing and procedures. We had two hundred and ten human retrieved samples over a period of fifteen years. Okay? Vin Morgan can, you know, be very accelerated at things he does, but he didn’t take two hundred and ten human cores in a week. That took some time to actually be done simply because it was retreatment for prosthetic reasons. The implants that we had were loaded from one hundred and twenty days to eighteen years. We got the fourth dimension of histology here, which is time. You know, you can have the three dimensions, you have X, Y, and Z, you can run measurements, but in this case, we got the most beautiful one in my understanding, which is the time. What happens over time? Alright? And then we did the typical histomorphometric histomorphological idea. So now you have seen plenty of animal and some human histology. What is this? Okay? Obviously, a Bicon to one year underloading. That’s what we consistently saw. This was the instrumentation line. This is old bone. This is new bone formed within the healing chamber. We see woven bone still here. You know, before one year, it doesn’t go away. Forget about it. But we already see some primary osteotic structures here that has that have lamellar structure around them. Okay? So it’s matching what we saw in animals, of course, in a different time frame. Alright? Then after five years, and if you remember, after five years, the mechanical properties change to cortical like. What are we seeing there? That’s a big osteonic structure in the center of the healing chamber, alright, running, you know, around the implant and very high lamellar multiple, iterations of remodeling right there. Meaning that biomechanically this guy is still adapting or has adapted already to the loads it’s being subjected to. Then the next one would be long term fifteen years plus. How many remodeling cycles have been here? Last time I counted was more than I could count because it happened in multiple directions. So Let’s get into what matters. Showing pictures is cool, but when you go to the numbers, that’s pretty awesome too. Let me go back one slide, simply because I wanted to show you that when you do bone to implant contact, there’s the degree of bone that you have in contact with the implant surface. And when you do BAFO, it’s bone area fraction occupancy, how much bone is actually occupying that healing chamber. Sure thing we did, two ten implants. And what we found, there was no effect of patient age, gender, arch, maxillary or mandible, something unexpected. Position, anterior versus posterior. Okay? Implant surface, no effect. Implant length, no effect. And implant diameter, no effect. What was actually important in this? Nothing but time. If you look at time at both measurable osseointegration parameters, they’re increasing. Okay? And that’s why this is really, really cool. If you’re if you can boost your osseointegration through, you know, adequate design, you get very fast healing. You get that particular morphology to evolve to something that is cortical like. Over time, no matter what, if it’s, you know, a male or a female, you know, how old the person is, in general, you’re gonna get an upward trend. So you’re gonna keep integrating as you remodel. Alright? And this is by far the most valuable dataset generated by my group at NYU. Okay? So going back the beginning, considering that the interplay between microgeometry and surgical instrumentation allows adequate environment for rapid osseointegration. Just remember, take for granted that most implant systems do not, but they will soon change Alright? Because of this, as you remember, this is a 3i implant, two weeks and four weeks in vivo. Beautiful. Bone to implant contact at two weeks. Between two and four, you get this remodeling taking place. Some bone forming already from the old wall toward the implant surface, so only so much the surface can do. Alright? Then let’s start from the beginning. Get the adequate macrogeometry plus surgical instrumentation. What are you gonna get? You’re gonna get adequate interaction between your osteogenic tissue and your implant surface and your old bone walls. So cells can freely travel right there. Okay? As I have shown, what can we do to actually boost that osseointegration? You can do surface chemistry, add, you know, let’s say PSCaP, plasma sprayed calcium phosphate, and you can do cold plasma to do that. Or both of them will further increase. Now moving from there, right, when you go from macro plus surface surgical instrumentation plus the surface, what else we can do? We can actually tag biomolecules on it that will further accelerate cell migration, proliferation, and differentiation. So you’re gonna get faster healing, as we can see here in the surface, at one week in vivo and at the osteogenic tissue within the chamber. Okay? Another thing that you can do is something that I’m gonna be doing with Jeremy Mao from Columbia, is to seed stem cells in there. Can we further accelerate healing there? Then we don’t have to wait until the cells get there. You see, that’s the that’s the whole point. If you can place an implant that is already seeded with cells, those cells, as soon as they interact with the biofluids, they start differentiating into bone forming cells. That’s pretty awesome. So we don’t have to wait then until the cells are actually there. Okay? Then adding macro geometry, surgical instrumentation, surface engineering, surface boosters, what can we do? Again, we can always look at the size and format of the healing chamber to maximize how much bone we get over time. Correct? Then, you know, after adding all this together, microgeometry, surgical instrumentation, surface, engineering boosters, chamber size, you do get rapid bone filling with adequate vascular and cellular content which will lead from woven bone formation, three dimensionally very fast, towards something that looks like already a bone morphology with a lot of primary osteons on it. Okay? A lot of lamellar structures there. From there, okay, these are animal studies. Okay? So we got these guys here, and now I’m gonna start showing that from then on, it’s only time that matters. You’ve seen this. This looks like an early osseointegration slide from an animal, but this is from a human where you have that primary osteonic structure right there with some woven bone with it. The lamellar bone is actually substituting the woven bone formation that was there earlier than that. After five years you get this very peculiar morphology which happens to be a cortical like, aversion like system. Okay? And as you remember, we were able to prove by mechanical testing and mechanical instrumentation that those mechanical properties are higher than what we had before five years. And as we go on, long term fifteen years plus, what we end up getting is this. After all of that, you keep increasing your osseointegration levels. Alright? And I do hope that I was successful in delivering this ridiculous amount of information today to you. I think this is one of my last slides. I’m not here to sell anything. This is the data as it is. Welcome to visit New York. I’ll email you the data if you wanna play with it. It’s never a problem. But I think that at thirty six years of age, I’m already telling a story, and that is pretty cool. And that means that the work has been well done from the beginning, and I don’t take credit for that. I take care I give the credit away for the people that actually educated me, not only when I was in dental school, when I was in surgery, when I was in engineering school. After I finished everything. I was a postdoc. And people at NYU that have been, you know, basically watching my back and nurturing me to become a better professional than I was when I got there. Okay? All that I did, again, I worked hard, and I looked for the funding. Alright? And I was the mechanic or the monkey that actually placed all these implants. Alright? And other than that, I think that we go back to that slide where we have the ideal implant. So you understand microgeometry better than I do by now. You understand that microgeometry is very important so long you understand microgeometry. Surgical instrumentation goes along with microgeometry, and we still have a lot of research to do here because there is something to be gained osseointegration wise, velocity wise, through surgical instrumentation. I’m positive of that. And then we have to combine with the different microgeometries, right there, and surface engineering techniques that we currently have. And I know exactly where we’re going. I don’t remember where this picture is from, and who cares anyways. But I do remember that at a point in time, I was within all these cities in less than a week. And that was pretty ridiculous, and I was giving talks, I was doing surgery in Paris, and then went down to Rio, and I was in New York as well. You know, I know exactly where we’re going. We’re going to make a difference in the future, and the ultimate winner of this is going to be the patient. Alright? And first, the patient, then the professional because they’re gonna have something very reliable to work with. And and then I would say the professional gains, and then we take over orthopedics as well because that’s what we’re doing next week through spine fusion and designing surgical hardware for spine fusion based on the technology that has been developed for dental implants. K? Very plain and simple, and I would like to acknowledge the most important people in my life, are the students and collaborators. They are absolutely the body and soul of the work. As I said, I am the cash collector, the fundraiser and the mechanic. The funding sources of course are very important, have been important, and they will be always important. NYU for actually putting up with me. The different departments, different schools, different divisions, different campuses, they have been absolutely great to me and I wouldn’t be where I am if it wasn’t for the people at school. Thank you very much.