University of Alabama at Birmingham
Professor and Director of Laboratory Surgical Research, Department of Prosthodontics and Biomaterials, Division of Orthopaedic Surgery
Jack holds a PhD in metallurgy and materials science. His research activities since nineteen sixty eight have emphasized tissue responses to synthetic biomaterials. He’s arguably the foremost authority in the world on bone. He obviously publishes and lectures extensively. Ladies and gentlemen, Jack Lemons. Thank you, Jack. Mr. Chairman, colleagues, it is indeed an honor to be in Boston to have been invited to present today on some activities over the last years. It’s also an honor and a privilege, to have been involved with many of you and throughout the world now for approximately forty years of my life. A part of that and an important part to what we discuss today initiated in the late nineteen sixties when I had the privilege and subsequent honor to meet and interact with Mr. Tom Driskell, an individual that we honor today. Additionally and subsequently over all of these following years, Fred Weekly, who we additionally honor. And primarily in the nineteen nineties, but over the years, I’ve been given the privilege to interact directly with Vin Morgan, Dr. Morgan, and the individuals at Bicon. And importantly to today’s lecture, and what we have been doing, as Bicon and associates have supported our graduate students, over the different studies that we have done, they’ve only asked one thing of us. Tell us the information and tell us the truth. So I feel it’s indeed a privilege to present to you without really a bias towards one implant system or another, but rather simply what we have learned from conducting primarily in vitro studies on surgical implants. Now the reason that I’m able to stay here, stand here, and stay here hopefully, excuse me, stand here, is based on graduate students and residents. I have the privilege of interacting with dental students, giving lectures throughout my history of being at the dental school. Additionally, I have orthopedic residents and interact with the faculty in residence and those in orthopedics. And importantly to what I do, also engineering and bioengineering. So therefore, I see data from three different disciplines and it’s indeed so fortunate to be able to tell you that at this stage there’s no more successful reconstruction done in musculoskeletal reconstruction than the dental implant. And we didn’t start there forty years ago, but we’re there today. So what I’ll provide today is experiences over these years of interactions. And because of the students, we’ve had the privilege to present in the community approximately six hundred presentations, and approximately half of those have gone to peer review publication. And that’s the students. And I certainly want you to recognize the importance of their contributions. From the nineteen sixties, we were considering primarily the physical considerations. We were looking at dental implants as a part of musculoskeletal reconstruction. And our primary focus, being a sub part of what all of you do has been primarily the designs and the materials. It started here. When I became involved at the School of Dentistry, we were extensively involved in a wide range of what was called at that time and called today the subperiosteal implant system. We were dealing with the platforms, with simple superstructures, these made of cobalt alloy. Subsequently, dealing extensively with the oral reconstruction considerations of what was called the Hader Bar and other systems for simplification. Eventually, the tripodials and other systems with and without hydroxyapatite for avoiding the mandibular nerve, and subsequently over many years with Dr. Robert James and others, with the two stage systems extending to the ascending rami, but providing support through multi fenestrations in the implant system. Additional part of that and a part of the data came from what was called the blade and plate systems. Within these systems, we dealt with vitreous carbon, we dealt with aluminum oxide, we dealt with tantalum, titanium alloy. On this particular slide, you see a wide range of designs from throughout the world, some with titanium nitride surfaces, some with modifications of all types, titanium plasma spray, but that database helped us to understand the interaction with bone. These continue today in a variety of forms, so we’re again given the opportunity to have follow ups that include not only root form systems, but many of the systems used extensively in the community. Within the root forms, we had a wider range, and this grouping includes implants where we had some type of investigation. Vitreous carbon, zirconium, zirconium oxide, aluminum oxide, a variety of metals. We see in here the old Greenfield implant that we looked at in terms of the technology that it was made in the early nineteen hundred’s to cast cobalt alloy. So it’s the dream of an engineer, a bioengineer like myself, to have so many options and things to investigate. Additionally, as presented by Charles English in the California Dental Journal, we focused primarily on the root form implants. At this stage, the question was the advantage or disadvantage of hydroxyapatite or calcium phosphate coatings generically, as they might improve, integration. And one reason for including this slide, which I’ll include later, is that within this system, we see the earlier implants at this stage, the Stryker system, both with and without the hydroxyapatite coatings. So therefore, looking at this history over a few years, we therefore gained information about the contiguous interfaces between implants and bone for titanium, zirconium, iron, cobalt, gold, tantalum, and alloys thereof. Additionally, with regard to the ceramics, we gain information with aluminum oxide, zirconium oxide, calcium phosphates, carbon, carbon silicon, and related compounds. And even though not presented here, in the community at large, we gained information on the various polymerics, polymethyl methacrylate, acrylic, PMMA, polytetrafluoroethylene that, Dr. Balkan talked about earlier with regard to guided membrane and other uses, polyethylene terephthalate or the polymer Dacron in the commercial community, and most extensively with various dental implants made of polyethylene. Those have been removed from the community due to biomechanical reasons, but continuous membranes. Now our considerations from the nineteen sixties have been the tissue and tissue interface and how these synthetics might interact. So we’ve dealt therefore with the hard and soft tissue and the questions of the relative merits of different types of integration, and that has included over this period fibrous integration, osseous integration, and combinations thereof. Here’s an example from one experiment in our laboratory demonstrating the conditions of fibrous integration. The implant was in the position on the right hand side of this slide where the erythrocytes are shown in this histological section, and you see this zone of several hundred micrometers of fibrous tissue that separated the implant from the bone. Now, do these types of interfaces have the opportunity for long term function? And in orthopedics and dentistry, the answer is yes. But on a relative basis, there’s an advantage. For osseous integration, and here I show you imposed a retrieval. This was a device placed by Dr. Leonard Linkow, New York City, New York. Carl Donath and myself, Carl in Germany, myself in Alabama, were given the opportunity to analyze the interface. This implant had been in function for a little over nineteen years. Now this is titanium against bone, and the relative merit here is this is a fully maturated stable functional bone over these nineteen years. And here’s the example taken from Dr. James rather than one of our slides showing the conditions of what’s called fibro osseous integration. Please recall that twenty years ago, we spent a great deal of time debating the relative merits of these types of interfaces. Our focus then, since the sixties, has been biocompatibility and functionality, but it’s also longevity and practicality because many of the systems that were in use did not continue on practicality, cost benefit ratios. But again, once the part that we were involved with was simply design and material as a small component of what was going on in the community. We were able though to publish global tables, and here I present one table from a publication now more than twenty years past, where we were looking at the role of force transfer and the potential influence of material. And here the materials are ranked from the upper part of the slide to the lower part of the slide in terms of changing elastic modulus, which then directly influences the contiguous strain at the interface with the bone or soft tissue. And what one sees in the middle of this slide is that we have titanium titanium aluminum vanadium and hydroxyapatite, which have continued today. This is carried over to the community, and there’s a fundamental basic science that has evolved. We have been an interactant in that basic science. And here I show you the graphic from Dr. Frost et al. This is Lance Lanyon. People throughout the world, have come to understand better the biomechanics of bone stability. And here is shown the relative changes in bone with microstrain distribution at the interface, realizing that in the lower zone we have the conditions of what’s called trivial loading. We call that, disuse atrophy of bone. We have the central region where we have stability. We have a situation where we have stasis of bone. And then as we reach the higher magnitude strains, we end up with what we call microtrauma or trauma to the bone. So therefore the achievement through design and material has been to have dental implants be designed and used in a way where they’re in the midsection, where we have stability of bone over the long time, over the long term, or what we call physiologic loading. The other direction I’ve now expressed about the load transfer or force transfer at the interface. Additionally, within the program, one would look at the elements of the contiguous interface, and here’s the same table repeated. And you notice on the right hand side of the table, there is the question of adjacent bone or bonding to bone. And what’s critical in looking at this slide is once again we have a wide range of materials that have been tested and evaluated functionally in bone. But we see in the middle of the graphic that again titanium titanium aluminum vanadium and hydroxyapatite have a yes yes statement, when it comes to not only contiguous bone, but the interaction of the bone, at that interface, which has been a part of the experiments that have been conducted. Now here I show you an example from histological studies. On the left hand side is then the interface and the way that interface was developed in a primate in our laboratory program was to introduce microstrain or micromovement at the interface. So this is a biocompatible material that in the absence of microstrain, we would have had what would be called osteo or osseointegration. But in the presence of microstrain, we see the fibrous connective tissue. Now what is probably equally critical if we add impurities to the interface deliberately or there’s a circumstance where the interface has been altered intentionally or unintentionally, you have a similar phenomenon that the bone reacts to that chemical biochemical environment, again, to give us a fibrous tissue interface. So these again are controlled laboratory experiments, but we have found that that carries over to the clinical theater directly. So the definition then of biocompatibility from our perspective has been minimal harm to the host and the device within the biological and physical limits of the system. So information to answer that and to have a surety of biocompatibility has been based on laboratory, which have been more basic science, laboratory in vivo, which has been laboratory animals, which have been basic and applied, and at least within some perspectives, the clinical aspects of studies, have been relatively applied. I do not mean to say here that many of the clinical studies have not been basic science, which they have, but that is the way we have viewed the information. So within this transition period, to take us from where we have been to where we are today, we have then separated, somewhat artificially, the various areas of investigation into the surgical preparation and placement considerations, the restorative considerations for the crown and bridge, and finally the maintenance considerations of hygiene and care. I think it’s critical when we then compare these databases that we think about the data that one analyzes. It’s been our experience within our university and also reviewing in the community and reviewing others that if we look at the relative merits and outcomes of circumstances, if you deal with the expert, the individual, here is the top of my pyramid, the one x reporter, this result in general has been very good, often exceeding ninety seven or ninety five percent outcomes over extended periods of time. A second question though becomes, as this is then moved from the central center investigator status to the community at large, which at least within standardized protocols would be going to 10x investigators working with the central investigator, the results are normally quite good but not as good as the single person doing it or laboratory or group doing it. And the critical part of this is that it makes the transition to a hundred or more investigators. Now within this, we have to accept basic probability statistics that there are many components that make up a successful implant system. And if we look at survivorship from a theoretical basis, this being the loss, if you will, of function, there’s the learning experience which plays a role, and with several of the implant systems the difficulty was in fact that each individual had an extended learning experience curve. There’s always the condition of error which is unavoidable in any circumstance, whatever the error might be. That could be in the implant system, it could be in the surgery, it could be in the restoration, whatever. It exists. But the key here in the long term we have the effects of aging of the host which establishes the risk benefit, but the intention here is to have this relationship, if you will, the stable long term successful system be as long as possible. And fortunately in dentistry, in surgical implant in dentistry, that now exceeds the other systems that I have the opportunity to work with. In summary of this section, with the evolution to current systems within the nineteen nineties and carried forward, with regard to implant designs, we have gone from many to a few, and the few now are predominantly root form designs and dentistry. However, it does not mean that the other systems have not continued. It simply means that the predominant investigative base in what we see is root form implants. However, within those root form implants within the commercial market, we see many shapes and sizes of root forms. If we think about the implant biomaterials, the same experience has been as with designs, in that we’ve gone from many to a few, and most of the systems today that we interact with are either titanium, the alloys of titanium, primarily titanium, aluminum, vanadium, and calcium phosphate coatings and or surface modifications. However, today we see many microtopographies and chemistries being introduced to enhance healing associated with the surface conditions. So therefore, if we think about the current systems and the tissue interfaces and functional integration, we have many to a few, primarily now what we call osteointegrations. But then a focus has been in our research and other research in the world for methods to enhance early bone healing through implant surface modifications, which will be a focus now of the discussion. So within enhanced healing, we’re really talking about early restoration being one of the aspects. Another is medical treatments for longevity, and Dr. Jeffcoat at our university before coming to Pennsylvania started our program. So we continue to look at a wide variety of treatments for maintaining soft tissue and bone health. So if we look then at the time events of bone healing, the key issues in bone healing, are essentially manipulation of what we can do at the bone interface, before the remodeling of bone, and the optimization is intended to decrease the times for the events that take place and while simultaneously improving the quality and quantity of bone. Now if we think about what might slow this optimization, I think the literature and the prior experience demonstrates clearly, that if we assume an appropriate patient and treatment selection delivery, then an unclean implant surface or site can minimize optimization, a damaged osteotomy, as we know, mechanical, chemical, thermal trauma to the bone. And I think importantly to the current considerations, in that if we have introduced interfacial micromotion exceeding a few hundred micrometers or some number per implant design, that can then prevent the early healing as one would desire. Now, our involvement here, that includes then the Bicon system, has been the question then of the bone formation, and we’re here comparing what we call appositional bone formation going back to the early publications from former years versus callus formation, which we have primarily dealt with previously in orthopedic surgery. We had published this particular paper, now I believe in two thousand and four, simply making the point if we look at the sequence of events on a long time scale, we can compare events versus time from essentially milliseconds to years. So that includes then the events of tissue healing. Now I’ve re expressed that in a table. In seconds, we’re dealing with the organic deposits on the implant. Within minutes, we’re talking about the beginning of the clotting and the fibrin and the cells that arrive. Within days, but less than seven, we’re talking about resolution of the inflammatory response in the absence of infection, the neovascular structures that begin and do form, days four to seven vascularization in the beginning of osteoid, subsequently the osteoid and the ossification, the immature bone that’s going to be forming after a week, and then finally the mature bone where we get into months. So what we’re dealing with is influencing what happens in this period within weeks to enhance what we call early bone formation. Now this has been published fairly extensively and I refer here to the long term studies of Larry Goretto, Gene Roberts, many other people where we’ve interacted. And they’ve laid out very clearly the sequences in that in five to seven days we have the start of mineralization, we have the growth characteristics over weeks, and they’ve pointed out that appositional growth from the front of bone where the osteoblast would exist is at approximately one to three micrometers per day, and this is mediated by the osteoblast. However, callus formation, which is the penetration of the clot and the subsequent formation of the vascularization proceeds at a rate that’s substantially higher and in the range of ten to fifty micrometers per day. Now maturation again is over months and where we see the increasing density and strength of the bone, but what we’ll be talking about today is the earlier period. Within surgical placement, one aspect of that then that influences what happens with regard to appositional, versus, callous formation, is the question of fit and fill. Within fit and fill, if one looks at a screw design implant, a rod or bullet shaped implant, or a plate shaped implant, they primarily fit the osteotomy if the surgery and the implantation goes according to schedule. So therefore, if I take a midline cross section of schematic drawings, the red lines would represent the contiguous bone interface, and the issue here, is that the primary mechanism then of the bone fill is by appositional growth. We’ve then been making a comparison with other designs, and on a comparative basis, if you look at a midline section again schematically of either what we would call a plateau design, a thin design, or a porous design, what’s critical here is the primary mechanism of the bone formation here is a combination of both appositional and callous formation. Taking information from the literature, here from a historical and a slide, that was published in two thousand and three, appositional healing on the average would be about two microns a day. So if one makes a calculation of the gap then, it would take about five days to fill in ten micrometers, fifty days a hundred, and two hundred and fifty days for five hundred. So the fit is absolutely critical to the rate of healing and stabilization. Additionally, it depends upon the trauma to the bone because subsequently the turnover of bone depends upon the microstrain that would have been introduced at that interface or the trauma or microtrauma during the bone preparation. Additionally, if you take a normal implant that is intended to be placed into a fitted osteotomy and it’s placed into a surgical osteotomy where you’re at the perimeter of the boundary of the threads, the healing takes on a very different characteristic. Here again, taken from the literature, is an example of the types of healing that one sees with these designs if it’s healing with a combined callus mode. Now, with regard then to the plateau fin or porous implant, this then heals by a mechanism. Here shown, again taken from the literature, the formation of the vascular structure and subsequently the trabecular bone or the bone callus that fills in the space where we have an osteotomy that is here shown at the perimeter, and we see this bone filling in. So therefore it’s possible by this mechanism to fill a space five hundred microns or micrometers in-depth within about seventeen days. Simple calculation. And importantly to the system, this bone goes on to maturation and then I’ll show you later in a very few minutes I hope, the subsequent results of long term evaluation of what this bone looks like after healing by this mechanism. So therefore, one concludes from these studies in the literature and our own studies that there’s a very different characteristic in bone healing type and kinetics in that bone formation rate, that the callus formation rate significantly exceeds the appositional rate within existing dental implant systems, which depends upon the fit and fill of the implant design compared to the surgical osteotomy. Now the next part of this then, if one then accepts that microchemistry or microtopography at the interface can then further enhance this healing, we asked the question about elemental transfers and attachment and also microtopography. Now this goes back to a slide from thirty five years ago, where we were comparing then a variety of conditions at the surface. And this schematic was really making the point that if you looked at calcium phosphate or other modifications at the surface, you really can change what happens in terms of the nature of the organic that is laid down and the subsequent interactions with the bony tissue. This then was carried forward to the many experiences that we saw and others saw with regard to root form implants and even subperiosteal implants, and we’re now looking at follow ups on many of those over the long term in terms of the stability of the bone interface. Now, again, I make the point that within this quadri of implants, this wide range of systems that could be evaluated, we also had the Stryker implant system, subsequently the Bicon implant system, with and without the calcium phosphates. Now we calculated in a laboratory experience with a master’s student that if one considers what happens with the calcium phosphate compounds of plasma spray origin, there’s about five micrometer thick zone of transfer on a two hundred millimeter squared surface area of implant. That’s an average implant. And that leads to point six to one point two milligrams of calcium and phosphorus, which then could be a local delivery system. So therefore, as one looks to the future in ways that one might deliver, there are multiple ways to alter surface chemistry, one being the IBAD treatment that you’ll hear about shortly, where one can then potentially upregulate osteoblast and metabolic activity in bone. This leads me then to recognizing two of the students recently. One will be the next speaker, but a few years ago, Dr. Coelho in our program conducted his master of science in clinical dentistry evaluating the question of this surface modification and bony reaction. This study was combined with one of the PhD students in our time who’s now at the University of Connecticut, Maria Advincula. And Maria was a physician by background but studied also the surface chemistry and subsequently has carried forward with that research. Now we were concerned at that time with the Bicon system as one component, and we were looking at the as machined oxide with either calcium phosphate or IBAD treatments. And here we’re talking about ion beam assisted assisted deposition, IBAD. We looked at the roughened surfaces which were aluminum blasted. We looked at the oxide, the calcium phosphate, the IBAD and did a variety of analytical techniques within the systems at the university to characterize the surface, scanning electron microscopy and chemistry, the photoelectron spectroscopy, corrosion, wetting, profilometry, x-ray diffraction, and then implanting, which is Dr. Coelho’s component. Now here’s what these surfaces would look like, which you’ll see again by scanning electron microscopy. Here would be then some of the analytical work from SEM showing the chemistry of the surface. These IBAD treatments are in amorphous zone, but you here see the presence of the calcium and the phosphorus. That was carried over to the photoelectron spectroscopy, and again showing that we had a very thin zone of the calcium phosphate as an amorphous compound that then could be delivered to the tissue during early implantation. Now as a part of this, Paulo then completed his, master’s work and extended those studies to Brazil. Here would be an example of one of, Dr. Coelho experiments showing the animal model where multiple implants were placed and subsequently sectioned. The sectioning for his master’s degree considered then the issue of what happens in the bone, as one moves away from the implant surface or along the implant surface. And this was done circumferentially around the implant, and this particular bone was analyzed not only by histomorphometry structure, osseointegration, but also in terms of tetracycline labeling, and the activity of the bone growth. And here is a composite slide from Dr. Coelho, simply making the point that if you look at the contiguous interface for the IBAD treatment compared to the control treatment, it’s statistically significantly different in a positive mode in that there’s enhanced labeling at the contiguous interface. And I’ll not continue that because Dr. Coelho is here. Now we’re now involved in a new paradigm. Today, after my lecture and after I hear the session at the break, I’ll be negotiating with the National Institutes of Health for a ten year activity, which is a consortium called a Biomedical Research Partnership. Now we proposed three years ago that we evolve a system to look at these types of systems in cadavers. We process at the university six hundred a year and in the system at large, five thousand a year. And we proposed to the National Institutes of Health that it would be desirable to look at outcomes where we would not be looking at an implant or tissue at removal, but rather what was in place and in function at the time of death of the patient. Now the mission of the university clearly is education, research, and service. We then look at this paradigm where we have said for a very long time that an important part of education is experience in terms of outcome. So therefore we’re moving as others throughout the world, primarily in part from a European model, to the evidence based dental education. So our component of this now is sort of analyses of explanted devices and relationships to clinical outcome. The way the system has worked throughout our history, which was proposed and now has been funded for the long term, is that we’ll be looking at projects, theses and dissertations where we start with an observation at the tissue interface or the clinical outcome. We then develop hypotheses, we conduct investigations, and then subsequently publications. Now the key to this is control of the process and the patient distance confidentiality, which is now under our protocols. But what we’re doing now is identifying, removing, and analyzing, and then subsequently going to peer review of the results. So the critical part for all of you, if you do participate, we will be seeking in the next year participation, is collection of the relevant clinical information, the removal of the specimen as a rod or cylinder or from a cadaver, and then we will compare then the in situ or en bloc conditions for these different implants. Now what’s critical with most of what we do is that the dental implants are initially fixed like a pathology specimen in ten percent neutral buffered formalin, and that’s the way we would normally receive them. They’re then in controlled package with minimal damage for transfer. We then look at the macro clinical observations and make an x-ray from the clinical theater. We look at soft and hard tissues, functional outcomes and reason for removal. We have gross observation and contact x rays. We have macro and microphotography at the beginning. And subsequently now in a new program that is just initiated, we look at commuter assisted tomography, CT and micro CT, and then compare that with the histological sections combined with scanning electron microscopy and micro and nano hardness, and then where indicated chemical and biochemical studies. Now the micro CT, we have found to be a phenomenally useful tool, and we’re in the beginning of setting up fairly extensive analyses using these methodologies. The advantage of this is you can look at implants to bone, you can look at bone graft, and then you can make direct comparisons on the same sections with either multiple or central sections through the midline. Here’s an example, a three-dimensional image of a study that we’re now involved with with a tricalcium phosphate as a bone graft material. This specimen comes to us from Italy. This particular bone graft micro CT, is then multiple. And here we see the section. Now this is a hundred and five hundred and fifty micrometer section, so it’s not the higher resolution section. But here we see the structural integrity of the bone in the front region, the mid front region, the mid back region, and the back region. And what’s critical of this, about this is we have the capability of separating by density and comparison grafting material and bone, maturity of bone, and the nature of bone for comparison with histomarphometry. Now the advantage we see to all of this then subsequently, the advantage we see to this is the extension to a variety of implants and the same types of questions. Now the current micro-CT system is at a hundred and fifty. We now move to the newer section at twenty five micrometers, is the same as our non decalcified sections. We have controls for relative densities. We can, essentially identify the bone graft and the dynamics, make a comparison. Another part of this, and I think as important as anything that I’ve talked about today, is the results of what’s happened in the coordinated studies throughout the world, but primarily, in this regard with regard to the Bicon system. And we’ve then looked at the interfaces for fin implants going back not only to the titantodont, but also the Omni system, other systems that were available, and have asked the question, is there something unique about the bone and the stability of the bone with regard to the plateau and fin designs? Now these are human explants, a small number, that have been lost due to prosthetic considerations. And here I’m focusing on the Bicon system. Here’s what we see. This would be three different implants, end section, end block, and the histomorphometry. Now full data are collected with regard to the nature of the bone and the character of the bone, but I simply point out to you the nature of the bone and what’s fundamental and so unique in these systems across a variety of systems, and here I show you three more, all relatively long term, is the nature of this bone with the existence of the normal marrow vascular canals. So this is truly functional alveolar type bone. But more importantly and probably critically, the nature of this bone is that it takes on, where needed, a haversian structure for maximal force transfer. So therefore, we believe at this stage, and this is a hypothesis, that this type of bone has the capability of adjusting and adapting to functional load over the long term. And we believe currently to be proven by quantitative comparisons in laboratory animal experiments that these systems will offer an advantage in terms of stability over the long term. So in summary, the overall process of healing and maturation of bone structure, remodeling for longer term assessments greater than five years of plateau design dental implants leads to a mature and functionally oriented Haversian type bone. And we’re finding that repeatedly for the fin and plateau designs. Now where are we going? It’s really fascinating to think about the future and what I hear in all of the meetings is what’s called immediate loading, which I call immediate restoration because I find so much variability in what individuals call loading. Now I believe that if there’s excessive loading or excessive micromotion at the contiguous interface, we’re gonna go back to fibrous tissue. However, what we’re finding within the immediate restoration systems, including the micron, is that we appear to have osteo integration, because there’s control of the system at this stage of the development of the field where it’s appropriate that this continue, which is a significant advantage clinically from the perspective of many. From our perspective, from the research community, over my forty years, we have moved from the macro systems here, from the device system and the construct, through the properties, ever decreasing capability or improving capability to analyze in terms of dimensions and microns or other measures. So where we are today is we’re over here in the analytical capability that all of us have in the laboratory. So we’re actually now talking about mechanisms of interaction as opposed to gross observations and opinions. You noted on my opening slide, I have said opinions. My thoughts are that we ask simply too complicated questions when we began many of our experiments. We were not strong enough to really deal with the basic science issues. The world has changed. We now are in a position, I think collectively, to deal with basic science questions and answer quantitatively results associated with outcomes. Now where are we going? I have the opportunity to chair two committees, one in dentistry for surgical implants and dentistry associated with the International Standards Organization and the American Dental Association, and then with the American Medical Association and the Orthopedic Academy associated with TC 150 within the orthopedic community. And what I’m finding within that community within the last five years, we’ve now moved to a position of what we call combination products. And we believe that will be the future. And that’s the issue that you’ll hear about in this meeting, and that’s controlled release of combination products where we’re modifying the surfaces of implants to have those implants accomplish outcomes that we would not have recognized previously, and then to continue to have a stable interface. Now here I want to give very special credit to Tom Driscoll. Tom has had this idea for many, many years and has presented, multiply, the opportunity of controlled release of calcium phosphate compounds while maintaining a stable oxide interface for long term function. I believe we’re there. The second part of this is the combination of synthetics and organics, which we read about in the community, and this is now called tissue engineering. Within the standard societies where I interact, we call this tissue engineered medical products, which includes the dental products at large. But importantly within this area, we’re now dealing with the controlled release of growth factors as mitogens and morphogens to influence what the cells do locally. And in my opinion, there’s a great deal of science yet to be done, but the biological sciences are moving so rapidly and advancing so rapidly that I believe that within decades this will be a reality and truly will move into the domain at some time where we’ll have regenerative medicine, we will be regenerating tooth structure and other structures as natural products. I’m not sure that I’ll be in the research community, I hope I am, when all of this will happen. But my opinion is is where we are today, which is essentially two thousand and five in this era of the two thousands, is we will really find it difficult to improve on something that is working with more than ninety percent success at twenty years. So therefore, within our National Institutes of Health grant and what I hope to participate in is a direct comparison where we use what we do today as a platform to ask the question if we improve the surface or improve the way that it’s delivered and its function, will it be better than what we do today? And also realize from statistical principles that we’ll have to look at thousands before we’ll be able to answer that question. Let me close by saying how pleased I am to have had the opportunity to come here, visit with you today. I apologize for my ineptness in operating the controls. I don’t seem to have mastered the system yet. But on the other side, I look forward to the discussion when it’s possible to have discussions with you individually or subsequently at the end of the lecture. Thank you very much. Do you want to take a question or two now? We actually have a minute or two if you like for Jack to answer a question or two, if there are any from the audience. Do we have any questions? I have a question. Jack, can you extrapolate the business of the fin design with the bone having the Haversian systems there? Can you extrapolate that to the shoulder at all? Or does that not come into play there? Yeah. It’s a valid point, and I put in the issue of the sloping shoulder as a summary. It’s not been the focus of our research. But I do believe that in the system, as you look at the sloping shoulder and you look at what’s coming out of the finite element modeling and analysis and the long term clinical results, that particular design offers the opportunity for force transfer in that region for maintenance of bone. Now the second part of it, I think equally critically, is how does the plateaus below that influence the system at large as we look at the sloping shoulder? But I do believe that the hermetic seal, the absence of purulence or other material locally, what we call peri implantitis, is equally probably as important. Now, do I know and can I extrapolate? No. Do I think we will find the answer in the future? Yes. So therefore, Dr. Morgan and others through the investigations here are supporting a number of studies at different universities investigating that aspect of the dental implants, but it’s not been the primary focus of our investigations. In your exam, we have on bone formation, and then you had greater than three months when remodeling occurs. No. Is is that the same remodeling that Gene Roberts first described? Because as I recall, in his model, he said it didn’t it didn’t begin until, oh, close to the first year in terms of true physiologic remodeling. Now has that changed? At that point, he called it we’re going from juvenile bone to load bearing bone. But then he said the true remodeling didn’t occur till considerably later. True. Depending upon the definition, bone remodeling, in my definition, is where you have osteoclastic resorption and principal turnover of the bone to make a stronger, more dense structure. And that happens in the long term, the so called sigma one, sigma two, sigma three that Dr. Roberts described. Now the point I attempted to make here is the focus of the research, today is on what we call immediate restoration or immediate loading. And the question is, can you enhance the bone formation at the stage before you get to the, essentially, the remodeling? Can you influence the modeling phase? And I believe that’s where the action is, and that was the point I attempted to make. But there’s no problem with definitions. I fully agree with the way that Dr. Roberts and Goreto and others have expressed it. But one of the interesting phenomena that they described that we did not talk about is this enhanced wrap phenomena or turnover phenomena at the contiguous interface. And I believe that’s a part of the microtopography biomechanical force transfer in that few micrometers adjacent to the bone. So I’m really talking here and attempting to talk about what happens in the first weeks or months and not what I would call bone remodeling. So it’s the bone formation through the beginning of modeling, which is normally associated with trabecular bone. Am I helping? Yes. Okay. Thank you. There’s another there’s another question from a gentleman just in the middle here. Thank you, Tom. Thank you. From Indonesia. I would like to ask you, You said that the bone formation via Callus formation is faster than appositional growth. Is it true? And you can get a good quality, Haversian bone. How do you explain that? Let let me re explain because I realize that, I’m taking license here, and going somewhat beyond the normal interpretations. What I’m comparing and what I’m discussing is the effect of having bone near an implant surface as you would have at the perimeter of the plateaus. Now that bone will react. That’ll be a stable bone for a very short period. But it will react very quickly through the reformation of the osteoblast on the surface to grow sequentially towards the implant. So that then, that bone formation, if the bone is not significantly traumatized, that bone is going to grow towards the implant. And that type of growth has been shown, multiply, to be a relatively slow rate of formation of bone, being on the average maybe two micrometers a day. We confirm that with multiple studies of tetracycline labeling and measuring between the labels. Now I make the point in contrast. If you have an implant design and an osteotomy where you now have a clot that would be like a fracture in the long bone, where you have this clot, there’s a vascularization of that space that takes place within the plateaus or the fins that now allows the vascular canals to be present and the formation of bone locally as trabeculae. And if you look at the fill rate of that space in callus formation, it’s at least ten times higher. So therefore, the opportunity to stabilize a thinner plateau can, under ideal conditions, be at a rate that can be ten times higher. Now that does not mean that the other systems cannot work appropriately and correctly in early restoration, but it rather means that you may have an advantage with regard to the time required to fill in a space with regard to the plateau and fin design. Now we also found that the plateaus are an advantage compared to the fins because that distance is so much greater in the fin, but I didn’t get into that. Now the second part of it though, which I think is equally important, is that the bone subsequently takes on a different anatomy. And that’s also true if you have a large crypt or a large osteotomy and you have a screw type implant. That bone that forms around a screw type implant is very different. Now I didn’t include the slides today, but it’s also very different if you have hydroxyapatite or not in terms of the way that bone forms. But what’s most important here, is I see a potential advantage in the short term and the long term for the combination where we have an osteotomy that fits the perimeter, that’s stabilized where it’s an advantage biomechanically, and then subsequently the filling in of the clotted area within the implant for subsequently stabilizing and then converting to a Haversian type bone that can be very stable and dynamic over the long term. Now I hope other investigators will, or perhaps we will investigate what happens at that interface with the metallic for this type of bone. Because see, we do not know that. We only know for the screw type implants, how dynamic that bone is. So there are investigations to be done. I apologize. I rambled. Thank you. Thank you, doctor.