Ricardo Trindade

Background and Objectives: To integrate the available published data on patients with oral lichen planus (OLP) rehabilitated with dental implants, as well as to review the recommendations for OLP patients receiving implants. Materials and Methods: An electronic search was undertaken in February 2019 using five databases. Publications reporting cases of patients with OLP and rehabilitated with implant-supported oral prosthesis were included. Results: Twenty-two publications were included (230 patients, 615 implants). The overall implant failure rate was 13.9% (85/610). In patients with oral squamous cell carcinoma (OSCC) the failure rate was 90.6% (29/32), but none of these implants lost osseointegration; instead, the implants were removed together with the tumor. One study presented a very high implant failure rate, 76.4% (42/55), in patients with “active lichen planus”, with all implants failing between 7–16 weeks after implant placement, and its conflicting and incongruent results are discussed in detail. There was a statistically significant difference between the failure rates in implants installed in different jaws (maxilla/mandible) and when implants of different surfaces were used (turned/moderately rough), but not between patients with reticular or erosive OLP types, or between male and female patients. If OSCC patients and the cases of the latter study are not considered, then the failure rate becomes very low (2.7%, 14/523). The time between implant placement and failure was 25.4 ± 32.6 months (range 1–112). The mean ± SD follow-up was 58.9 ± 26.7 months (1–180). Conclusions: When the results of the one study with a very high failure rate and of the cases that developed OSCC are not considered, the dental implant failure rate in OLP patients was 2.7% after a follow-up of approximately five years. Recommendations are given when treating OLP patients with dental implants.

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.

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: Osseointegration mechanisms are still not entirely understood.Purpose: The present pilot study aims at demonstrating the involvement of the immune system in the process of osseointegration around titanium implants, comparing bone healing in the presence and absence of a titanium implant.Materials and Methods: Fifteen New Zealand White rabbits had one osteotomy performed at each of the distal femurs; on one side, no implant was placed (sham) and on the other side a titanium implant was introduced. Subjects were sacrificed at 10 and 28 days for gene expression analysis (three subjects each time point) and for decalcified qualitative histology (six subjects each time point). At 10 days, the three subjects for gene expression analysis were part of the six subjects for histology.Results: Gene expression analysis: at 10 days, ARG1 was significantly up‐regulated around titanium, indicating an activation of M2‐macrophages. At 28 days CD11b, ARG1, NCF‐1, and C5aR1 were significantly up‐regulated, indicating activation of the innate immune system, respectively M1‐macrophages, M2‐macrophages and group 2‐innate lymphoid cells, neutrophils, and the complement system; on the other hand, the bone resorption markers RANKL, OPG, cathepsin K, and TRAP were significantly down‐regulated around titanium. Histology: at 10 days new bone formation is seen around both sham and titanium sites, separating bone marrow from the osteotomy/implant site; at 28 days no bone trabeculae is seen on the sham site, which is healing at the original cortical level, whereas around titanium implants, bone continues into organization of more mature cortical‐like bone, forming a layer between the implant and the bone marrow.Conclusions: The presence of a titanium implant during bone healing activates the immune system and displays type 2 inflammation, which is likely to guide the host‐biomaterial relationship. At the same time, bone resorption is suppressed around titanium sites compared to sham sites after 4 weeks of implantation, suggesting a shift to a more pronounced bone forming environment. This suggests two important steps in osseointegration: identification of the titanium foreign body by the immune system and the development of a bone forming environment, that at tissue level translates into bone build‐up on the titanium surface and can be perceived as an attempt to isolate the foreign body from the bone marrow space.

Background: The last few decades have seen a progressive shift in paradigm, replacing the notion of body implants as inert biomaterials for that of immune‐modulating interactions with the host.Purpose: This text represents an attempt at understanding the current knowledge on the healing mechanisms controlling implant–host interactions, thus interpreting osseointegration and the peri‐implant bone loss phenomena also from an immunological point of view.Materials and Methods: A narrative review approach was taken in the development of this article.Results: Osseointegration, actually representing a foreign body reaction (FBR) to biomaterials, is an immune‐modulated, multifactorial, and complex healing process where a number of cells and mediators are involved. Thebuildupof osseointegration seems to be an immunologically and inflammatory‐driven process, with the ultimate end to shield off the foreign material placed in the body, triggered by surface protein adsorption, complement activation, and buildup of a fibrin matrix, followed by recruitment of granulocytes, mesenchymal stem cells, and monocytes/macrophages, with the latter largely controlling the longer term response, further fusing into foreign body giant cells (FBGC), while bone cells make and remodel hydroxyl apatite. The above sequence results in theFBRthat we call osseointegration and use for clinical purposes. However, the long‐term clinical function is dependent on a foreign body equilibrium, that if disturbed may lead to impaired clinical function of the implant, through abreakdownprocess where macrophages are again activated and may further fuse intoFBGCs, now seen in much greater numbers, resulting in the start of bone resorption – due to cells such as osteoclasts with different origins and possibly even macrophages degrading more bone than what is formed via osteoblastic activity – and rupture of mucosal seals, through complex mechanisms in need of further understanding. Infection may follow as a secondary event, further complicating the clinical scenario. Implant failure may ensue.Conclusions: Dentistry is still to embrace the concept of the biomaterials' healing‐ and immune‐modulating effect when in contact with body tissues. The presented knowledge has the potential to open the door for a different interpretation of past, current, and future observations in dental implant science. From a clinical standpoint, it seems recommendable to react as rapidly as possible when facing peri‐implant bone loss, trying to reestablish a foreign body equilibrium if with some bone resorption.