New York University
Assistant Professor of Biomaterials and Biomimetics, Director for Research, Department of Periodontology and Implant Dentistry
Yes. I do work at NYU. I’m an engineer. I actually do only surgical research unless otherwise requested. And with that said, I do a lot of material science and engineering as well. I work at the department of biomaterials and biomimetics. I have been recently assigned after someone was let go of the perio and implant department at NYU to direct the research of that program. And it has been a delight even though it has substantially decreased the number of decisions that I can make on a day because that actually took some of my time. And due to the engineering background, as all of you know here, NYU is the only true global university. I’ve been assigned along with Nick Tovar, who is, someone who works with me at NYU, to teach at the division of engineering at, NYU Abu Dhabi. And why did I accept that? Simply because that’s the the best student pool in the world that you can possibly think of. All the kids that apply to NYU get and have the best applications. Are actually sent there with a full ride housing and everything. So that’s what I’m looking for. I’m looking for bright kids so I can interact with and and get things done. Now, there is something that you can notice in the slide that’s Paulo G. Coelho et al, so I cannot do this alone. And actually, was thinking about if we put together all the people that work with us at NYU, I think we’ll be able to fill half of this room, just for the collaborators. And that’s why the group is so prolific when it comes to scientific throughput. Alright? So getting started, implant design short and long term bone effects. I don’t think that there’s anything more ambitious than talking about implant design, but I think that the group and I don’t speak for myself, I speak for my group. Two of the biggest collaborations, one is Nick Tovar, who’s sitting right here, and the other one is Dr. Suzuki on my left from Tufts University. We have today probably the largest program, and I’m saying the largest, not the best, because as you get bigger, you know, things change a lot. But we try to keep the quality up there. And what makes me and the group uniquely qualified to talk about the implant, the Bicon implant design relative to others is not the almost forty something publications we have with Bicon, It’s the other hundred that we have with the other systems. So we can make direct comparisons in that. So without further delay, let’s talk about Osseointegration. I don’t think it gets anything, you know, better than this. This is a twenty three years in function human retrieval. It’s actually almost twenty four. Okay? As you can see, the bone is very well adapted to the implant, and as we’re gonna see later, the mechanical properties of this bone actually happens to be just like the mechanical properties of cortical bone. Guess where this implant came from, posterior maxilla. Can we measure the mechanical properties between these plateaus? We certainly can. We have done it, we have published on it to show how things are. So this is a classic slide that is out of one of the review papers that we have written. Advances over the last forty years in osseointegration, when you think about the mechanisms concerning initial and long term bone implant interaction, those are still to be determined. And that’s why I still have a job in this business. And despite the vast literature, the content is not hierarchical and it’s highly contradictory. Okay, I challenge any individual in this room to actually read the whole literature and come up with a better implant design. You’re not going to come up with anything better than what we currently have because that’s what what our literature allows for. Okay? Unless we do what we have been doing over the last twelve years, is building a solid database so we can have informed design rationale guidelines, that’s gonna be primarily impossible. Still on that, thus we have a blind library of size proportional to the investigator’s conflict of interest. Do I really need to elaborate on this? I don’t think so. Right? You know who is the Straumann guy, who is the Nobel guy, even some of the Bicon guys, you know who they are. So there is conflict of interest all around this business. Alright? And the result is actually very sad. It is unlike what we have in civil mechanical or aerospace engineering is that we do not have an informed design platform for implant designing. Alright? And unfortunately, we’re primarily marketing driven, and that doesn’t help the ultimate user of implants, which happens to be the patient. Right? So and the progress has been very slow relative to other areas. Now design is the most ambitious topic. Alright? And I am going to concentrate on macro geometry a lot. A little bit on micro, nothing on nanogeometry because there is no true nano science in implant dentistry or even orthopedic surgery these days. And I will talk about surgical instrumentation. Alright? I think that orders of magnitude of what has been researched, of course, the one in blue is the one that has been researched the most. Second, I don’t know, probably in nanogeometry, and the two that that are actually more important, that is you’re gonna see based on the data happens to be microgeometry macrogeometry and surgical instrumentation. Those are the ones that actually play the biggest role in osseointegration, short and long term. Alright? Believe it or not. And, you know, we’ll see with the data that we have generated. So the ideal implant, concerning microgeometry, you would have to think about the physical, of course, you need the bulk integrity, but it does have a big role in biology. And from a biological standpoint, you may have a very fast healing plus bone evolution to cortical like high mechanical properties over time. That’s something that we have proven. The microgeometry and the nano, those are actually ad hoc to your microgeometry and your surgery, okay, or surgical instrumentation. So, the micro and nano, they have to work in tandem with the microgeometry. Alright? And the surgical instrumentation has to do with two things, simplification of the procedure along with gaze and off cost integration. We have been playing a lot with that, and we have been looking into very interesting results. So into the microgeometry, if you go talk to different companies, they have the highest surface area, the best design, and the the best whatever that you can think of. Right? How can we tell them apart? Right? And they always claim that basically every implant system is going to us integrate in the exact same fashion, regardless of their shape and surgical instrumentation. I don’t think so. Our data has been telling us that that’s absolutely not the case. So let’s look at classic study that we have performed years ago, fact. Well, not too long, it was published two thousand nine, where we had six dogs, two times in vivo, two in four weeks. We used the proximal tibia model, and I can’t always explain why we do that. It’s just to facilitate matters and gain time. Alright? Three macro structures with distinct surgical protocols, histomorphology and histomorphometry. Okay? Now this is the most important slide of the lecture, lecture. So let’s, you know, go over it in detail. So we have a short pitch implant, you have a large pitch implant, and you have a plateau implant right there. Right? So the dash line happens to be the outer diameter of your drilling system. So what’s gonna happen to the short pitch implant? Basically, you’re going to go in, you’re going to have an incredible amount of primary stability, right, and you’re gonna put a lot of compression in bone. Going to the large pitch scenario where you have an osteotomy, a drilling site that is actually slightly over drilled relative to the inner component, inner dimension of the of the tread. Basically, what you’re gonna end up having is that you’re gonna have some primary stability, which is totally dependent on the thread design that you have there, but you’re gonna end up with that void space that is going to be filled with blood, provided that you have a a surface that would actually keep that blood clot in place, which is very important. Alright? You have primary stability, but in the same scenario, you end up having a healing chamber right there. Okay? So just by looking at the short and large pitch scenarios, of course, you’re gonna have two different healing scenarios right there. And then you end up having the plateau where the osteotomy goes all the way to the outer diameter of the implant, and you have a very large healing chamber there. And I will have to walk out of here so I can actually point some of the histologic features there. This is something that we’re not necessarily proud of as we started doing research. Every time you open a lab somewhere, there’s a curve, but a learning curve as to how to do the histology, and it varies from place to place. But anyways, you do have the short pitch implant, the large pitch, and the plateau. And at two weeks, basically what you have is that it’s not projecting very well, but this guy right here instead of the bone being pretty much formed like we have in these two scenarios, that’s woven bone right here. That is actually bone that’s going away. Okay? So very different scenarios. Would you expect this much bone forming at two weeks even though the canines heal faster than we do? I was I certainly was not. Right? From two to two to four weeks, we did have time to actually allow for some remodeling, but what’s going on at four weeks for the other two scenarios is that you have plenty of bone and that bone is evolving at a very rapid pace. Okay? Now, this micrograph may not look very familiar to you, but the person who did this actually is a person that works in my department who won the Max Planck Award for anthropology. He’s a bone specialist. And winning a plank is like winning two Nobel Prizes because it’s only awarded every other two years. Alright? And basically, what I want you to take out of this, this is the large pitch implant right there. You can see where the drilling took place and you have plenty of new bone formation right there. The darker it is, the more disorganized it is. Correct? On the plateau design, you have plenty of woven bone formation and you have primary osteons forming right there. And what happened in this scenario? I cannot see from here, but I’m pretty sure you can see from there. There’s white dash line here right at the interface. And basically that’s the amount of bone that had to go away before the osteoblast traveled from the pristine bone towards the implant surface. So what do we get out of this? First, you’re losing stability, of course, because that bone has to be taken away somehow. And then, if you think about it, why does it even make any sense to actually treat the surface of the implant? If you’re gonna put a lot of compression of bone, the giant cells will have to do a catabolic resorption here, and then the osteoblasts have to travel right there, all the way from the bone towards the surface. Surface engineering makes no sense if you want to enhance osseointegration. Whether in this scenario, you can actually put a very rough surface in there and keep the blood clot in there. There’s no cell mediated cleanup in healing chambers, and therefore, you start healing very fast. Okay? It’s instantaneous, basically. So, and also the rate which this here happens is two to five micrometers per day. And if you look at the error bar here, the the micron bar, that’s about two hundred micrometers. So you divide that by two hundred by five, that’s the number of days that you need to close that gap. Whereas in this scenario here is thirty to fifty micrometers a day in three dimensions. So we can actually do some very interesting things with that. Alright? So on this study, we had compare comparable osteoconductivity. The healing chambers actually happened to heal thirty to fifty micrometers a day. And whereas the apposition, where is the tight fit, there has to be a cleanup, and then two to five micrometers a day from the old bone towers, the implant surface. Okay? And we had comparable integration rates, which is bone to implant contact, which to me makes no sense whatsoever. But again, let’s look at one of our iJommy publications right there. This is an MK three, which is the Brånemark type thread design at two weeks in vivo. Now, I ran out of laser pointer. So, basically, what you’re seeing oops. Go back. Right here. No. The green one’s not working anymore. No. It is. Basically, in this guy here, you see at two weeks, it looks like beautiful interaction between bone and implant. Right? Can you put mechanical loading on this? I would say, yeah, it looks interesting for load bearing situations. And then that’s what you get at four weeks. Everything that’s dark blue in here means that went away and then bone hatch regrow in there. In an animal, it grows very fast in humans. Well, it takes a little longer. If you’re thinking about putting load from top to bottom in this situation, where what is the last place that you wanna be losing bone in this scenario? That’s pretty much where the dark blue is on the two micrographs on the on the left right here. Right? You go from a scenario like this to something like this. This is basic. This is basic carpentry and mechanics. K? Put a lot of compression depending on on the thread design. So that’s something that the companies are starting to avoid. So now getting into one of the most cited studies that the group has, which is pretty much comparing intramembranous bone healing versus the oppositional, the healing chamber versus the tight implant that goes in there. Pretty simple design, eight beagle dogs, extraction followed by eight weeks healing, implants were placed remaining for three, five, eight, and twelve weeks in vivo. So now we have four points, and you’re gonna see where this is going to take us. Is it important for the short term, how you actually have your implant design and your osteotomies? Yes, is. But you’re gonna see that long term, that’s where we gain the most. Alright? Now looking at this scenario, and some of the measurements that we make is pretty much the bone to implant contact. Contact. So if you look at the healing chambers right there, we get pretty much zero at time equals to zero during placement. Whereas the other one goes pretty much a hundred percent. Right? It’s sort of a no brainer to think that, well, the the scenario on the bottom is best, but you’re gonna see what happens over time in vivo. So at three weeks, the plateau would form implant right there, this guy here on the left, right there. Okay? Basically, what’s going on there? You can see bone growing from the osteotomy line towards the healing healing chamber. You can see bone forming right in the middle of the healing chamber, and you see bone forming from the walls of the healing chamber towards the center of the implant. Alright? Easy enough, three-dimensional growth in every single direction at thirty to fifty micrometers per day. You know this already. What’s going on here on a tight fit implant right there? The cleanup is taking place. In an animal, yes, it takes much less than in a human, but whereas this one is losing stability, this one is gaining. Now going from three to five weeks on the healing chambers, of course, we have more bone formed, and we have something called primary osteonic structures forming in there. Whereas, you don’t see that on the interface of the tight fit tight fit implant. And that’s when things start to get really interesting. Okay. Looking at healing chambers at eight weeks, you have plenty of bone formed that’ll give it, and you have a lot of primary osteonic structures. And with that said, you have blood vessels and you have the cell content needed for you to remodel gaining mechanical properties fast over time provided that the mechanics of the system allows you to. Correct? What do we have going on for the tight fit? That’s pretty much a carbon copy of what was going on at five weeks. Right? At twelve weeks, we have large osteonic structures, and you’re gonna see where this is gonna take us because you applied mechanical loading to this and you’re going to end up gaining a lot of remodeling and thereby mechanical properties. What do you have down here in this scenario at twelve weeks? Pretty much the same type of structure you had at five weeks. Okay? So, pretty much this surface modification and placement of biological factors and eventually stem cells. Where does that make sense? On a scenario where you’re to have a tight fit and the osteoblast is not going to see a surface until much later, or putting growth factors in healing chambers or cells or whatever you want to enhance osseointegration to keep the blood clot in there and attract cells. Alright, so that’s if the profession is going towards the biologics or you know, higher level surface modification, this one is uniquely positioned in order to do that. Okay. Then of course, we have something we have very interesting results when it goes to one healing chamber size, we went ahead and did something that was key for implant designing, alright, different healing chamber sizes. And what did we gain out of this? Bicon gained information regarding the healing kinetics of different healing chamber sizes, and more daring designs rationalized by an informed research platform. Some of the newer implants, some of the short implants that are there, they have different healing chamber sizes. And with it has been thought about as to how much osseointegration power the implant would have as well as its kinetics. So very interesting. What do we get at three weeks in vivo in a healing chamber? We have bone growing from the osteotomy wall towards the implant. Healing chamber, okay? We have aisles of woven bone forming within the center and bone forming from the surface. This was in fact the first time that I saw contact osteogenesis. Alright? Basically, you go into a healing chamber, and if you look at the cells that are here, those are osteoblasts. And this osteoblasts, this osteoblastic line happened to populate at one point in time earlier, the implant surface right there. And as it walked, forming bones, some of them got trapped behind, and actually those became osteocytes. Okay? So that is true contact osteogenesis. Does that happen on a tight fit implant? It’s physically not possible. Okay? So, going back here to right. The contact osteogenesis, you have multidirectional bone growth throughout the chambers, so rationalizing the rapid filling that we get on these guys. From three to five weeks, you saw plenty of woven bone. What do we have here? We have lamellar bone forming the primary osteon, osteonic structures. So it is different already. Alright? And that you do not see on tight fit implants. So let’s see how this goes as we move towards more, you know, more time in vivo. Getting this primary osteonic structures, rapid development of bone mechanical properties. Right? And what is important is that you have high vascular cellular content and modeling and remodeling potential. Okay? How will mechanical properties evolve if that is your scenario? And this is something that we had the privilege of getting the samples from Vin as he was retreating some patients where, you know, we got the human samples, we had all the information needed to run decent statistics on it, and the results are absolutely mesmerizing, if you think about it. Published in two, actually three high level journals in three different publications. So the first one concerned only the titanium, the roughened titanium surface, the IntegraTi surface. Things do not look nearly as beautiful as they usually do when you have an animal. You can actually you get to do whatever treatment is necessary after you retrieve the samples. So that’s what we got. Courtesy of Marcelo Suzuki, we made a point of not having these slides very thin because we may lose some of the structures that we were looking for. And basically, this is what we got. At an eight year retrieval, plenty of bone to implant contact well, that’s a given. And we had, you know, a Haversian system, you know, between the plateaus. Could we measure the mechanical properties back then? No, we were not equipped to do that. The one micrograph on the left is just the transmitted light, and the other one is the polarized light, which tells us, shows us about the directionality of bone, which is something you know very well that is important as, you know, it directly relates to Wolff’s Law. Okay? Then looking at another eight year retrieval, you can see the Haversian and Volkmann canals in there. That is exciting. And then we started to look at those guys and say, that’s got to be anterior mandibular, and some of them actually were not. So we’re puzzled, how is actually this thing happening. Alright? Ten year retrieval. I know they do not look fantastic from a slide processing standpoint, because we made a point of having this, but the canals are there. That’s exactly what we wanted to see. Thirteen years in vivo, as you see after ten years in vivo, you start to get a big osteon right in there. Big remodeling site right there. And that’s mechanically something that we can see even in finite element analysis. We can actually correlate those two different things right there. So then people were concerned about, well, those are titanium implants. What happens if you have hydroxyapatite coated implants in there? And there was nothing different than this, but this were more, this study was more fun, because we had implants that were eight months after placement, two months after loading. So we still had what you see darker in there as woven bone, and things evolving towards, you know, the osteonic structures in there. This is one of the micrographs I like the most, which is twelve months after placement, six months after loading. You do not see woven bone there anymore. You see lamellar bone and evolving towards the osteonic structures that were there to begin with because of the healing mechanism of the healing chambers. A very simple concept. Then we go three years after loading, the same thing you see the Haversian and Volkmann canals in here, you see the osteonic structures, multiple remodeling sites right there. That means evolution. Where did that come from? It came from the original design of the implant and where and and its interplay with the osteotomy. Okay? You have the space, you have blood clot retention, that if you have a decent surface. Okay? And having the blood clot retention in there, cells can migrate towards the surface, populate that surface while and form bone from the surface, from the middle of the chamber, and from the osteotomy wall, because that’s unnatural for the osteoblast to actually hang on to and start forming bone. Okay? Five years after loading, I mean, we have hundreds of this in the lab and they all look like one another. Okay. They always evolve towards something like this, thirteen years in function. Alright. Big one, remodeling site here, and things evolving around the implant shape in that fashion. Twenty four years in function. So actually twenty three point, like, twenty three years and ten months. Look at this. That’s a Haversian system that is forming around the implant. The directionality is unequivocal because that’s how the implant actually is mechanically functioning stimulating bone to remodel in this fashion to actually be able to bear the loads that are being incurred on it. All right? Also courtesy of Dr. Suzuki as well. So then, yes, we saw something that nobody has seen before in dental implantology. The tight fit implants, they don’t change nearly as much the bone around tight fit implants. Do not change nearly as much as these did, and we were concerned to, you know, it looks like a virgin bone. Can we go ahead and do mechanical property testing of this with statistically credible clinical parameters, and we went ahead and did it. And basically, we had, you know, a bunch of variables there, jaw position, anterior posterior, coding, and in vivo time, and we wanted to know what were the effects of the different variables there. Anterior versus posterior, maxilla versus mandible, implant surface, and and here we go. Basically, happens is that we have somewhat high mechanical properties until about, what, five years? And after five years, this actually skyrocket to cortical bone properties. How did that happen? That has to do with all going all the way back towards the bone healing mechanism, where you get woven bone, which develops towards an osseointic structure. You give the mechanical loading to that bone, and that bone turns into a cortical like bone in the beginning, the first five years, and then it evolves through cortical bone mechanical properties all the way from nine to whatever years you can think of. Okay? What was important? Between plateaus, we had no differences in mechanical properties. The coating or the implant surface, that didn’t contribute at all. But the part that puzzles me the most is that anterior and posterior regions had no differences in mechanical properties, which is puzzling to some extent, and no difference in maxillary mandible from one to five years and from five years on, where you got the cortical like mechanical properties. So it is possible to actually stimulate bone towards mineralizing in a fashion where you get cortical like mechanical properties. And that is pretty interesting. So going back to the microgeometry, plateaus and healing chambers, it does play a significant role on the early healing, which is the fast bone healing of healing chambers. So you go from something with woven bone and rapidly starts going towards the surface that has primary osteonic structures. Well, we’ve seen that over and over. Alright. Something else, and that particular structure goes to a cortical like structure over time. So it has to do with the healing mode that you have, and then that will evolve towards something that is unique. So the unique healing leads to unique bone configuration over time. If you want to hold a short implant, what type of bone would you like to have? Just the lamellar one or something that is cortical like and properly aligned to to bear the loading? So, no, totally up to you. When it comes to this situation, the healing chamber also provides a unique condition for surface design and incorporation of biological factors and even cells. Okay? Since this is not a cell mediated dieback, you don’t compress bone and have to have giant cells actually clean that interface before you have new bone forming. So if you wanna benefit from your surface, from your growth factor, which we have done plenty on different implant designs, have a healing chamber. Your chances of success are much higher. Now, going from the macro and the surgical technique towards surfaces, which are nothing but ad hocs, and their largest research database is also from our group, and believe that our two key review manuscripts in there, the first one is the highest has the highest number of citations on journal biomedical materials research. Alright? And it also talks about the methods and all the things that we have been doing wrong over the years when it comes to actually analyzing implants. Implants. Right? Osseointegration. And the second one happens to be something more technical, where we look into the different surface parameters. But what’s the point of all this? Is that with the Bicon design, have twenty two manuscripts on surface evaluation. Different surface analysis, and, you know, we played a lot with this, and yet you haven’t seen anything beating the p s a j. Okay? It goes five, ten, fifteen, twenty, twenty two, and what did we learn out of this? Nothing beats the AJ surface. It doesn’t matter. I can try type one bone, type four bone, type twenty bone, if I go to to the hip. That one thrives in a much better fashion, much improved fashion. Alright? So nothing beats that Integra CP can refer to any of the pubs that are out there, regardless of the booster that we try to put on the titanium surface. And we have tried a lot of different things, including BMPs, plasma, you know, cold plasmas and other things. Nothing beats that guy in there. Now, there is something we can do about this guy, which happens to be, we can actually boost the Integra CP surface further. Okay? With biological factors and potentially stem cells, and that’s what my group is going to be doing with Jeremy Miles group in out of Columbia. So we’ll see how that is going to go. The final piece is the one that I think that we should be putting more effort when it comes to us integration research wise, which is the drilling technique. We have a bunch of papers out, but the only one with healing chambers is this one. And one thing that I wanted you to know is that there’s almost nothing available in the literature. We send a paper out to the journal editor. They said, well, we’re gonna take your paper, we like it, and can you expand on the introduction of the paper and provide more background? Then I write back, what background? We’ve been doing this forever based on books. And then you go to the book, there’s no reference as to what we were doing. Okay? So I think that we can pretty much change things around if we do the appropriate surgical drilling. So what we learned out of this study, we did fifty RPM versus nine hundred RPM instrumentation. The fifty RPM instrumentation, no irrigation at all versus the nine hundred, which was obviously irrigated. The lower drilling speed had slightly better results with respect to BIC and BAFO, which is bone to implant contact, and how much bone actually occupies areas between plateaus. And most important is that this wall here that was drilled. Okay? This wall right there. When you drill that under low speed, actually, you got lower dieback, of this drilling right there, because there will be dieback because of the trauma to bone. And how can we actually, you know, improve on this circumstance here? Basically, need to try other things right there. We need to expand this database so we can make an informed decision as to where to go with this. And we have done plenty of that as well, and and it changes how us integration actually goes. So design, once again, very ambitious topic, highlighting micro geometry. The micro and nano, actually not really out there, and surgical instrumentation. The two in red, I think it’s unequivocal. Those are the most important ones, and the ones in the middle are the ad hocs. Alright? And then a couple final remarks right here. It’s all about the interplay between microgeometry and surgical instrumentation. That is what is going to dictate how your implant is going to also integrate, and how fast that is going to take place, and how actually that bone is going to evolve into a cortical like bone. Surface treatment and biological factors are ad hocs in there. And, of course, good ones help a lot. We’ve put we have proven that over the years. Anything else? To us integrations, yeah, we can see a lot of things in healing chambers, and that’s where the future is going to be. So if all the companies are pushing towards biological factors, they will have to substantially change their design of surgical instrumentation. The macro geometry and the interplay between the macro geometry and the surgical instrumentation. Okay? And some companies are still concentrating on surface engineering while having an implant that goes in very tight. And that particular company was very funny because they’re having problems with their with para implantitis now, and they’re going to launch a new revolutionizing surface, which is grit blasted and acid etched. Something that hasn’t been around for the last thirty years. Right? Unbelievable. Let’s see what the name is going to be and what they’re gonna find with the microscope in there to try to sell it. Okay? Thank you very much. I know it’s a massive amount of information, and I hope this came across in a nice fashion. Thank you very much.