OLE JENSEN, DDS, MS, is a diplomate of the American Board of Oral and Maxillofacial Surgery and a fellow of the American Dental Society of Anesthesiology with a private practice in Greenwood Village, Colorado. He is also the founder of Ditron Dental USA. He lectures nationally and internationally; has authored seven textbooks on oral surgery, including The Sinus Bone Graft; and has published more than 100 articles in the literature.

Inside Dentistry (ID): What is the next frontier in the development of dental implants?

Ole Jensen, DDS, MS (OJ): We used to think about dental implants and how we could improve them almost exclusively in terms of metallurgy. I think we're going beyond metallurgy now, and we're going into bioactives and other things to make the metal more acceptable and improve healing. Before, we had done that by making the implant surface rough using different techniques. We've sort of taken that as far as we can go with it though, and the improvements now are commercial improvements-meaning not particularly scientific improvements. Surface treatments do show a little incremental improvement here and there, but these are probably much less than 5% or maybe even less than 1% or 2%. That's the environment that we are in with implant modification and abutment modification right now.

ID: So, the challenge now is really about the biocompatibility of the implants?

OJ: Correct. When it comes to implant survival, I'm kind of an outsider looking in. I'm an oral and maxillofacial surgeon, not a periodontist, a dental hygienist, or even a general dentist. So, I'm a super-specialized person who is creating a wound, delivering an implant, and then sewing it up and leaving-abandoning the patient in a way. And so, for me as an oral surgeon to attack this problem is unusual because I don't deal with maintenance or long-term follow-up, and my reference base is in the literature more than clinically. However, I do see the late stages of peri-implant disease where it's gotten so bad that you need to remove implants or do another type of treatment. And so, it has burned my conscience a little bit that the way we are doing things now is not really the best way to be helping people. I don't believe that we're managing implants in the right way.

Let me explain. The new way of thinking about the medical devices that we put in the body, including into the bone, is that they are foreign entities that undergo a foreign body reaction that is maintained by the body to try and keep them excluded from the body. When the bone heals around a dental implant, and we get so-called osseointegration, this phenomenon is not actually the body's friendly healing to an inert object that we previously believed it to be. We don't look at it that way anymore. We look at it as the body's protective mechanism to exclude the foreign element that has been inserted there as much as possible.

And so, if you have that as your new paradigm of what is actually happening with dental implants, that means that bacterial inflammation, infection, or chronic bone loss around an implant is mediated within the milieu of a foreign body reaction. And if that's the case, bacterial infection is a secondary invasion process. Tomas Albrektsson, MD, PhD, has noted that bone loss can occur from an aseptic event, like it does in knee replacements, for example. So, when aseptic bone loss leads to exposure of the implant, bacteria come in secondarily and really create a mess, which is the infection that we witness. That's the paradigm shift that we're in. It isn't fully accepted, but I have spoken and written about it. Two years ago, we published an editorial about it in the The International Journal of Oral &Maxillofacial Implants called, "Foreign Body Osseointegration."

It has been interesting to me that despite this tremendous change or pivot in the ideology of peri-implant disease and the maintenance, treatment, and immunomodulation of it, there hasn't been a big protest movement that's developed out of it and that people don't know quite what to make of it. In the periodontal graduate schools, I think it's still kind of in the process of being vetted. They are trying to understand, well, how does this work and so on. This is how it is in the United States but not so much on the European side, where I think they are ahead of us in this way. We need to realize that the dental implant is a foreign body element and that bacterial inflammation and infection is a secondary event, generally speaking.

ID: With that in mind, what are the main risk factors for developing peri-implant disease, and what can we do about it?

OJ: Well, I collaborated on a risk factor paper called, "Dental Implant Risk Factors For Peri-Implant Disease: A Narrative Review," that was published in Frontiers of Oral and Maxillofacial Medicine about 2 years ago, and in it, we identified more than 30 risk factors for peri-implant disease. This was kind of a stunning thing because most risk factor studies and meta-analyses end up mentioning 4 or 5 things. They talk about things such as previous history of peri-implantitis, diabetes, or medications that people are taking, but it's just a few things. Many of them then make statements to the effect that other risk factors that have been suggested are not statistically verified in the literature.

Based on our review of the literature, we came up with about 30 risk factors for peri-implant disease, and one of the biggest ones was the implant itself. Peri-implantitis doesn't occur unless there's an implant, right? So, the implant itself is the problem. And then the second problem is the surgeon who puts the implant in and the prosthodontist or general dentist who restores it. The implant itself and operator error are a great deal of the cause of peri-implant disease. The way that Albrektsson puts it, and I think it's kind of hyperbolic, is, "If an implant is placed properly, you don't get peri-implant disease."

That's kind of an extreme statement because if 20% of the implants over a 10-year period of time end up with peri-implant disease, then it's implied that we're putting them in improperly or restoring them improperly 20% of the time. And you know what, I think we probably are doing that. So, when you ask what we can do about peri-implant disease, I'd say there's a lot we can do about it. Many times, we're putting implants in or restoring them improperly, and I think that we just really need to up our game and raise the standard of care.

ID: Have we gotten to a point where clinicians are moving too quickly when it comes to placing implants and restoring them?

OJ: I don't know if clinicians are moving too quickly, but I do believe that a lot of the time they're not putting implants in correctly. It goes back to the issue of the implant that you put in, how it's made, what its structure is like, and so on. And then it's about the operator. When you're placing an implant to replace a tooth, for safety reasons, you want to keep about 2 mm away from any adjacent teeth. Why? Because a tooth is a risk factor. When teeth aren't taken care of, they become inflamed, get plaque around them, develop subgingival inflammation, experience bone loss, etc. Therefore, if we are placing our implants very close to teeth without a sufficient distance of bone, then they can get infected from the adjacent teeth.

Most of the time, manufacturers will say that 1 to 1.5 mm between implants and adjacent teeth is sufficient. But as I've looked at this, I think the recommendation is based on the realization that if they say that 2 mm or more is necessary, clinicians won't be able to place implants in a lot of cases. They're going to say what they can in order to maximize sales of their products. Well, there is a way to put a fairly wide implant into a space and preserve sufficient bone, and that is to place an implant with a narrow neck. If you put an implant in that has a straight wall or is even diverging outward, you're going to have decreased bone around the cervical part of the implant. But if you have a constricted neck, and there are several implants that do this, then it preserves bone volume there. For example, our Ditron implant is 4 mm in diameter, but the top 2 mm is constricted inward, which leads to 5.5 mm³ of additional bone volume preserved. Less titanium means more bone-less is more. So, if you have like a 7.5 mm site, you can kind of maintain a 2-mm distance from both adjacent teeth if you use a narrower implant or if you use a 4 mm diameter implant that's constricted at the neck and you're careful about placement.

ID: Is there a way to develop implants that will be more resistant to bacteria and infection once they're placed?

OJ: There are things that we can do. I'll address the hardware issues before I address the chemistry issues. First, I want to talk about the gap-the implant-abutment gap. This is a literal scandal in our industry. Let's say you have a Morse taper implant, such as a conical implant, for example. We've tested them, and sometimes the manufacturer can be pretty good, but it's not consistent. So, maybe about half the time you can get a Morse taper so it doesn't leak, but the rest of the time, you're having bacteria going in and out. That's one issue. Another issue is micromovement. You don't see this as much with some of the implants. For example, Morse taper implants don't move as much as some of the others. However, movement leads to percolation and also to small particles of titanium being leaked out or expressed into the bone and the peri-implant environment. These things can lead to a foreign body reaction, an osteoclastic secondary reaction, and so-called peri-implant disease.

So, the leakage from the inadequate manufacturing of implants is a scandalous thing that we accept, but the worst part of it is that it's iatrogenic. It's dentist and laboratory caused. I'll explain. Let's say a dentist buys an implant from a company, and the company has a very fine abutment that fits on it quite well, but the dentist wants to use a certain custom implant abutment. When custom abutments are used, it can result in a large microgap. These microgaps can be as large as 5, 10, or even 20 μm. When you know that bacteria are roughly 2 μm in size, it doesn't take much brain power to get that these microgaps can permit the ingress of a huge reservoir of bacteria, especially if the implant is demonstrating micromovement, and that's going to participate in the development of peri-implant disease.

When I decided to get behind the Ditron implant system, the first thing I looked at was the precision of the fit. They have a 0.5-μm gap. One clinical study that was done showed only 1% leakage. In a two-piece implant, you cannot completely eliminate leakage, and that's part of the problem of peri-implant disease. We should face up to it.

Now, let's talk about the chemistry. Is there anything that we can do to implants chemically to make them more resistant to bacteria? Well, we've made structural modifications to implant surfaces to resist bacteria, such as microgrooves and other features, but in the end, we've got a foreign body element that's sticking up through the mouth, through the tissue, and that's just not going to cut it. Something has to be done to the chemistry of the surface of the implant. Well, we've come up with a chemical process that can make any material antimicrobial, and we're studying it clinically now.

Let me explain what this is and what we're doing with it. Currently, we have four FDA-approved restorative products on the market in the United States that contain this chemical entity that kills bacteria on contact. The Infinix^™ system consists of a bonding agent, a universal composite, a flowable composite, and a bulk-fill composite. If you place a regular composite, even one of the top-selling composites in the world, within 24 hours of placement, a scanning electron microscope study of the surface of that composite will reveal that it is populated by a million bacteria. My partner says it's more like a billion bacteria, but regardless, it will be populated by bacteria and more so than the enamel in general. So, with traditional composites, we are placing a medical device-this composite filling-that is actually attracting bacteria. With the Infinix composites, 24 hours after placement, a scanning electron microscope study of the surface reveals no live bacteria. None.

It sounds too good to be true, but we have 25 publications over about 15 years studying the use of this chemical process in all kinds of materials, from metals and alginates to silicones and acrylics-almost anything you can think of. And it works. We are in the process of incorporating this process into all aspects of implant dentistry. Currently, we have a joint venture with a company called Sprint Ray, and we're going to be enabling the 3D printing of crowns, dentures, and fixed hybrid prostheses that are completely antibacterial. So, how does this antibacterial chemistry work? The most lethal chemical to bacteria, viruses, and fungi is ammonium. We use it all of the time to wash our floors and clean our bathrooms, and even some of the hand washes and stuff that we use are based on it. Ditron's antibacterial chemical formation is a silica with covalently bonded quaternary ammoniums that can be impregnated into or covalently bonded to a surface.

There is an antibiotic mechanism that is referred to as bactericidal, in which certain antibiotics kill the bacteria that are alive and present. Another mechanism is called bacteriostatic. This mechanism doesn't really kill the bacteria that are present, but it sort of interferes with the metabolism of the colony to weaken it and prevent the next generation of bacteria. What we are developing with this quaternary ammonium silica particle is a different mechanism. It is bactericidal, but it doesn't kill at a distance. Antibiotics kill at a distance. In fact, penicillin was discovered by Alexander Fleming because he noticed that the penicillin mold produced a little halo in which bacteria were not present. With the quaternary ammonium silica particle there is no drug-like effect at a distance; it's only bactericidal on direct contact. If bacteria are a certain distance away, which we determined to be about 10 μm, then they are unaffected. Because bacteria have to be in close proximity to be eliminated, we refer to the mechanism as "proximicidal."

When it comes to implants and abutments, we've developed a method of cladding the quaternary ammonium silica particles to titanium surfaces, and they kill bacteria, as well as any fungus or virus, on contact. We know that it works, but we still have to study it in different ways to see if there's any toxicity that may otherwise interfere with healing. One thing about antibiotics and materials such as silver or copper that have an antibacterial effect is that they leach out over time and decrease in efficacy. If you impregnated an antibiotic around an implant, it would leach out, and after a few weeks, the bactericidal effect would be gone. Our research shows that when quaternary ammonium silica particles are cladded onto the surface of a titanium abutment, they don't leach out over time. They are always there-chemically a part of the titanium oxide. If this chemistry can be successfully incorporated into the design of implants and their related components, they will be free of bacterial colonization throughout their lifetimes, which we've seen can be decades. I think that would definitely be an impressive development in the evolution of better implants.

ID: Do you think that technologies such as dynamic navigation and robotic surgery can help more clinicians to optimally place implants?

OJ: Yeah, I think so. I work with a Michael Block, DMD, who is a very experienced doctor, and he went to the navigation approach. When I asked him why he does navigation, he said, "Well, with navigation, I can accurately place an implant exactly how I want to every time. If I do it freehand or with a guide stent, I can get it 95% or almost all of the time, but I can't get it every time." He has kind of convinced me that this is the direction that we will go in now and in the future. It's a very, very precise method of placement that enables us to put implants exactly where they're planned to go, and we can kind of see in real time that the placement is appropriate.

Nonetheless, we have noticed that even when implants are properly placed with a good technique and appropriate position according to navigation or whatever method is used, some of them are affected by bone remodeling after 2 or 3 months, and we don't know why. Maybe it's a foreign body reaction. Maybe bone strain occurred that resulted in remodeling. Maybe there was

infected bone that needed to be removed by the body. We don't know exactly why, but after 2 or 3 months, a certain percentage of patients develop some bone loss, and it's a risk factor in the future. If there should be some inflammation that occurs, bacteria can seed on that area, and it can lead to peri-implant disease.

I just wanted to kind of get that out in the open because it's another radical concept that people don't want to take responsibility for. They, in an ad hoc way, want to blame the patient 6 to 8 months later for not brushing his or her teeth because now all of a sudden there's a millimeter of bone loss, or something like that. It has something to do with the process of healing that we don't quite understand but should actually address.

ID: Going forward, how should the profession approach implant therapy in order to improve the success of treatment?

OJ: One of the things that I'm currently working on is how to best treat the atrophic maxilla with implants. The profession has come up with all kinds of solutions, including sinus grafts, zygomatic implants, transnasal implants, pterygoid implants, and other procedures, but we don't actually know what the best thing to do is in these cases. We are currently working through an AI-powered process to try and calculate mathematically or physically what we need to do to treat these patients. Right now, we're finding success with all kinds of different methods, but we really don't know what the best thing is to do. To a certain extent, that could be said of all implant treatment. For all of the implant dentistry that we're doing, we really don't know exactly what the best thing is to do. I think that if we can have that amount of humility and openness, we can go forward from here, and in a really conscious and conscientious way, try to develop methods for placing implants and restoring implants that are scientifically, clinically, and humanly optimal for our patients.