**Preface to "Osseointegrated Oral implants"**

Osseointegrated Oral Implants: Mechanisms of Implant Anchorage, Threats and Long Term Survival Rate

Osseointegrated oral implants were first used clinically in 1965 at the Gothenburg University of Sweden, and then only in small numbers. There, the original osseointegration team, of which I was a participant, worked clinically and experimentally under the leadership of P-I Branemark to test osseointegration principles not only in the oral cavity but also as craniofacial and orthopedic implants [1–7]. Other pioneers of the early days were Willi Schulte of Tübingen University, Germany, and André Schroeder of Bern University, Switzerland, who published their first papers on bone-anchored oral implants in 1976, in all probability without knowing about Brånemark´s earlier work [8,9]. These three University-employed innovators became the fathers of the most used oral implant systems of our day—the Nobel, the Dentsply and the Straumann implants.

The present volume represents the state-of-the-art in oral implants today. Some interpretations may be too old and others too untested to survive the scrutiny of time. However, this is how scientific ideas usually develop. The pioneering team behind osseointegration was convinced that titanium was inert and that its incorporation in bone simulated a simple wound healing phenomenon [2,10], hypotheses that today are recognized as being incorrect. Nevertheless, the very good clinical results achieved with moderately rough osseointegrated oral implants with a 10 year survival rate in the range of 96–99% [11] meant that other hypotheses could be verified, despite some errors in interpretations. We learned countless lessons from the early work behind modern oral implants. In a similar manner, I personally consider those who believe marginal bone loss around oral implants to be solely dependent on bacteria to be on the wrong track, which does not preclude the future value of some of the findings of this research.

New valuable findings on osseointegration include a most interesting paper by Chen et al. [12], who present evidence that a novel type of osteotomy may preserve implant site viability by using a very low drill speed with the potential advantage of minimal tissue violence. Han et al. [13] present an in vitro study using 3D printed carbon fiber reinforced PEEK material that, in the future, may provide possibilities for applications in oral implantology, on the condition that the in vitro findings of the biocompatibility of this material can be supported by in vivo analyses. An animal study by Choi et al. [14] evaluates osteogenic cell behavior in a new manner by using ultrastructural techniques and immune flourescence analyses during the first 10 days after implant placement. The notion that oral implants must be rounded bodies belonged to our old convictions. In this volume, we learn about the potential advantages of changing the implant design to a tri-oval one. Implants with this design displayed significantly enhanced implant stability in the bone when tested in animal studies [15].

 Zipprich et al. [16] point out that the insertion of ceramic implants may cause more interfacial heat than the placement of titanium implants, indicative of the need to use a very slow drill speed with the ceramic devices. Stocchero et al. [17) analyze intraosseous temperatures when performing undersized drilling and report a negative impact on the bone some distance away from the implant. Duddeck et al. [18] demonstrate that our commercially available oral implants may be contaminated, perhaps having an effect on clinical outcomes. The effects of a novel type of electrolytical cleaning technique for implant surfaces decontaminated by biofilms is presented in two papers [19,20]. It proved possible not only to clean away the biofilm in vitro but also to re-establish osseointegration of a previously infected implant in a dog model. To the knowledge of the editor this is the first time we have seen evidence of re-osseointegration under such circumstances.

Three papers test potential improvements of osseointegrated implants in clinical settings. Lombardi et al. [21] evaluate factors that influence marginal bone loss during the first year after implantation, a time when most clinical scientists do not talk about peri-implantitis but, instead, of bone remodeling. Greater initial marginal bone loss was seen with deep insertion protocols, thin peri-implant mucosa and short abutments. Marconcini et al. [22] describe the tapered abutments that were found to result in minimal marginal bone loss in a one year retrospective study. Doornewaard et al. [23] present a three year prospective study of implant-supported mandibular overdentures in a split mouth model. The equicrestal implant placement was reported to yield significantly higher implant surface exposure.

Threats to osseointegration include marginal bone loss that, if continuous, may result in clinical failure. Currently, the most quoted reason for such unwanted marginal bone loss is what some investigators call peri-implantitis, allegedly behind all marginal bone loss after the first year of implantation. Schlee et al. [24] analyze their previously described electrolytical cleaning method and suggest that 100 million oral implants around the world may be infected and threatened by failure. I judge this great number of implants suffering from risk of failure to be unrealistic and rather based on unsuitable criteria for disease. However, the potential for reosseointegration in case of marginal bone loss may, nevertheless, be of substantial aesthetical importance. The electrolytical cleaning technique was not improved by simultaneous mechanical cleaning based on a 6 month randomized study [24]. Monje and co-workers [25] describe the peri-implantitis site-specific entity and present a traditional overview of predisposing factors for ailment. As previously indicated, I do not personally believe that implants and teeth are the same [26], nor do I agree with all bacterial interpretations of these papers. An overly strong immune reaction may likewise lead to marginal bone resorption. Having said so, bacterial attacks may follow secondary to strong immune reactions. Certainly, time will tell more about the right and wrong than our present reasoning.

The last part of this book is centered on immunological findings of osseointegrated implants, discussed in 8 different papers. Menini et al. [27] present a follow up of a previously published paper [28] that claimed plaque causes inflammation but not marginal bone loss. In the new paper, they demonstrate that some specific mRNA signatures appear to protect from bone resorption despite plaque accumulation. Coli and Sennerby [29] question the use of tests like probing depth and bleeding on probing that have been taken over from periodontology, but never independently assessed with respect to oral implants. Reinedahl et al. [30,31] demonstrate significant immune reactions to ligatures around titanium implants. Marginal bone resorption was demonstrated despite lack of implant plaque and all implants having been placed in a bacteria free environment in the tibia of research animals. These strong and adverse immune reactions to the implant/ligature compound caused marginal bone loss due to the immune system control of the osteoblast/osteoclast balance, thereby contradicting hundreds of previously published papers suggesting a direct bacterial attack due to the ligatures. Bacterial attacks in such cases may largely represent a secondary phenomenon only.

Trindade et al. [32], in a previous experimental publication, demonstrated that titanium gives rise to immune reactions. In two separate papers, Trindade et al. [33,34] confirm these observations, but the authors notice an even stronger immune reaction to materials such as copper and PEEK at 28 days of follow up in an in vivo study. It seems that the body accepts mild immune reactions, like those emanating from titanium implants, and reacts either by preventing osseointegration, like in the case of copper and PEEK, or resulting in marginal bone loss around already integrated implants if provoked by very strong/imbalanced immune reactions [35]. Christiansen et al. [36] examine marginal bone loss in total hip replacement cases and report a significantly different cytokine profile compared to the situation without bone loss, suggesting an association with innate and adaptive immunity. Naveau et al. [37] point out that osseointegration is a foreign body reaction, indicative of an immune response to oral implants in the normal clinical situation. Amengual-Peñafiel et al. [38] agree with these observations and refer to the functioning oral implant as being in a state of foreign body equilibrium. This is a new way to look at an oral implant that is in opposition both with the notion that titanium is inert and, further, with those who see titanium implants as similar to teeth

All in all, this book contains a collection of research that clearly increases our knowledge of osseointegration. The papers in this book will be repeatedly quoted and serve as inspiration for further research efforts in our discipline of oral implantology.

Gothenburg, Sweden June 10th, 2020

Tomas Albrektsson Professor emeritus of Dept of Biomaterials, University of Gothenburg, Sweden

Visiting professor of Dept of Prosthodontics, University of Malmö, Sweden

**Tomas Albrektsson**  *Guest Editors* 

#### **References.**

