In the field of biomaterials, an endosseous implant is now recognized as an osteoimmunomodulatory but not bioinert biomaterial. Scientific advances in bone cell biology and in immunology have revealed a close relationship between the bone and immune systems resulting in a field of science called osteoimmunology. These discoveries have allowed for a novel interpretation of osseointegration as representing an osteoimmune reaction rather than a classic bone healing response, in which the activation state of macrophages ((M1–M2 polarization) appears to play a critical role. Through this viewpoint, the immune system is responsible for isolating the implant biomaterial foreign body by forming bone around the oral implant effectively shielding off the implant from the host bone system, i.e. osseointegration becomes a continuous and dynamic host defense reaction. At the same time, this has led to the proposal of a new model of osseointegration, the foreign body equilibrium (FBE). In addition, as an oral wound, the soft tissues are involved with all their innate immune characteristics. When implant integration is viewed as an osteoimmune reaction, this has implications for how marginal bone is regulated. For example, while bacteria are constitutive components of the soft tissue sulcus, if the inflammatory front and immune reaction is at some distance from the marginal bone, an equilibrium is established. If however, this inflammation approaches the marginal bone, an immune osteoclastic reaction occurs and marginal bone is removed. A number of clinical scenarios can be envisioned whereby the osteoimmune equilibrium is disturbed and marginal bone loss occurs, such as complications of aseptic nature and the synergistic activation of pro-inflammatory pathways (implant/wear debris, DAMPs, and PAMPs). Understanding that an implant is a foreign body and that the host reacts osteoimmunologically to shield off the implant allows for a distinction to be drawn between osteoimmunological conditions and peri-implant bone loss. This review will examine dental implant placement as an osteoimmune reaction and its implications for marginal bone loss.

Bone anchored biomaterials have become an indispensable solution for the restoration of lost dental elements and for skeletal joint replacements. However, a thorough understanding is still lacking in terms of the biological mechanisms leading to osseointegration and its contrast, unwanted peri-implant bone loss. We have previously hypothesized on the participation of immune mechanisms in such processes, and later demonstrated enhanced bone immune activation up to 4 weeks around titanium implants. The current experimental study explored and compared in a rabbit tibia model after 10 days of healing time, the bone inflammation/immunological reaction at mRNA level towards titanium, polyether ether ketone (PEEK) and copper compared to a Sham control. Samples from the test and control sites were, after a healing period, processed for gene expression analysis (polymerase chain reaction, (qPCR)) and decalcified histology tissue analysis. All materials displayed immune activation and suppression of bone resorption, when compared to sham. The M1 (inflammatory)/M2 (reparative) -macrophage phenotype balance was correlated to the proximity and volume of bone growth at the implant vicinity, with titanium demonstrating a M2-phenotype at 10 days, whereas copper and PEEK were still dealing with a mixed M1- and M2-phenotype environment. Titanium was the only material showing adequate bone growth and proximity inside the implant threads. There was a consistent upregulation of (T-cell surface glycoprotein CD4) CD4 and downregulation of (T-cell transmembrane glycoprotein CD8) CD8, indicating a CD4-lymphocyte phenotype driven reaction around all materials at 10 days.

Background: Peri‐implantitis has been suggested to cause significant increasing proportions of implant failure with increasing time.Purpose: To assess whether implant failure rates in long term studies are matching the supposed high prevalence of peri‐implantitis.Material and Methods: This paper is written as a narrative review of the long‐term clinical investigations available in the literature.Results: Some implant systems have seen unacceptable marginal bone loss figures with time coupled to increased implant failure rates, resulting in the withdrawal of these systems. The reasons for such mishap are generally unknown, with the exception of one system failure that was found to be due to improper clinical handling. Modern, moderately rough implant systems have functioned excellently over 10–15 years of follow up with minor problems with marginal bone loss and implant failure rates within a few per cent. Machined implants have functioned adequately over 20–30 years of follow up. Implant failures occur predominantly during the first few years after implant placement. No significant increase of implant failures has been observed thereafter over 20–30 years of follow up.Over the years of our new millennium, scientific and technical advances have allowed the discovery of numerous molecular pathways and cellular interactions between the skeletal and immune system promoting the development of the interdisciplinary field called osteoimmunology. Nowadays, this knowledge has not only allowed the emergence of new etiologic paradigms for bone disease but also a new dynamic approach on the concept of osseointegration and MBL around oral implants, re‐evaluating our older disease oriented outlook. This facilitates at the same time the emergence of translational applications with immunological perspectives, scientific approaches based on omics sciences, and the beginning of an era of personalized dental implant therapy to improve the prognosis of oral implant treatment.Conclusions: Oral implant systems have been found to function with very good clinical outcome over follow‐up times of 20–30 years. Registered implant failures have occurred predominantly during the first few years after implantation, and there has been no significant increase in late failures due to peri‐implantitis.

This systematic review sought to analyze different experimental peri-implantitis models, their potential to induce marginal bone resorption (MBR) and the necessity of bacteria for bone loss to occur in these models. An electronic search in PubMed/Medline, Web of Science, and ScienceDirect was undertaken. A total of 133 studies were analyzed. Most studies induced peri-implantitis with ligatures that had formed a biofilm, sometimes in combination with inoculation of specific bacteria but never in a sterile environment. Most vertical MBR resulted from new ligatures periodically packed above old ones, followed by periodically exchanged ligatures and ligatures that were not exchanged. Cotton ligatures produced the most MBR, followed by steel, “dental floss” (not further specified in the studies) and silk. The amount of MBR varied significantly between different animal types and implant surfaces. None of the analyzed ligature studies aimed to validate that bacteria are necessary for the inducement of MBR. It cannot be excluded that bone loss can be achieved by other factors of the model, such as an immunological reaction to the ligature itself or trauma from repeated ligature insertions. Because all the included trials allowed plaque accumulation on the ligatures, bone resorbing capacity due to other factors could not be excluded or evaluated here.

Osseointegration is likely the result of an immunologically driven bone reaction to materials such as titanium. Osseointegration has resulted in the clinical possibility to anchor oral implants in jaw bone tissue. However, the mechanisms behind bony anchorage are not fully understood and complications over a longer period of time have been reported. The current study aims at exploring possible differences between copper (Cu) and polyetheretherketone (PEEK) materials that do not osseointegrate, with osseointegrating cp titanium as control. The implants were placed in rabbit tibia and selected immune markers were evaluated at 10 and 28 days of follow-up. Cu and PEEK demonstrated at both time points a higher immune activation than cp titanium. Cu demonstrated distance osteogenesis due to a maintained proinflammatory environment over time, and PEEK failed to osseointegrate due to an immunologically defined preferential adipose tissue formation on its surface. The here presented results suggest the description of two different mechanisms for failed osseointegration, both of which are correlated to the immune system.