Morphological and Molecular-Biological Features of Inflammatory and Regeneratory Processes in Peridont Tissues with Periimplantitis and Periodontitis.

A morphological and immunohistochemical study of periodontal tissues was performed in patients with chronic generalized periodontitis who underwent dental implantation. We studied 44 biopsy specimens from 21 patients (13 women and 8 men) aged 35-60 years with a diagnosis of periimplantation mucositis (7 patients), periimplantitis (8 patients), and severe chronic generalized periodontitis (6 patients). It was established that periimplantitis differs from periimplantation mucositis by a more pronounced inflammatory reaction with a clear predominance of plasma cells in the infiltrate, which captures the fibrous capsule around the implant, destroys it and further spreads to the bone tissue. Based on the immunohistochemical differences in SMA, VEGF, and Ki-67, it is concluded that periimplantation mucositis and periimplantitis are successive stages of progression of the same process. When comparing chronic generalized periodontitis and periimplantitis, the latter shows much more pronounced inflammatory and destructive processes in the area of the implant, due to the addition of immune inflammation, impaired regeneration processes, and destruction of bone tissue.

Onset, progression and resolution of experimental peri-implant mucositis at different abutment surfaces: A randomized controlled two-centre study.

OBJECTIVES: To assess the onset, progression and resolution of experimentally induced peri-implant mucositis lesions at abutments with different microstructures in humans. MATERIAL & METHODS: In a randomized, controlled, interventional two-centre study, a total of 28 patients had received 28 target implants and were randomly allocated to either partially microgrooved (test) or machined (control) healing abutments. The study was accomplished in three phases, including a wound healing period (WH) following implant placement (12 weeks), a plaque exposure phase (EP-21 days) and a resolution phase (RP-16 weeks). Clinical (e.g. bleeding on probing-BOP), immunological (MMP-8) and microbiological (DNA counts for 11 species) parameters were evaluated. RESULTS: The incidence of peri-implant mucositis at EPd21 was comparable in both test and control groups (60.0% versus 61.5%), but markedly lower at control abutments after a nonsurgical treatment and reconstitution of oral hygiene measures at RPw16 (46.7% versus 15.4%). At any follow-up visit (i.e. EP and RP), clinical parameters, MMP-8 levels and DNA counts of major bacterial species were not significantly different between both groups. CONCLUSION: The onset, progression and resolution of experimental peri-implant mucositis lesions were comparable in both groups.

An immediate peri-implantitis induction model to study regenerative peri-implantitis treatments.

OBJECTIVES: The aim of this study was to evaluate the validity of the immediate peri-implantitis model to test regenerative therapies in peri-implantitis defects. MATERIAL AND METHODS: In an immediate peri-implantitis model in beagles, the mandibular third premolars were extracted, and dental implants were immediately placed in the distal extraction sockets. Without a healing period, experimental peri-implantitis was induced by ligature placement for 3 months. In the conventional peri-implantitis model, dental implants were placed in the healed mandibular fourth premolar region and were submerged for osseointegration. After 3 months of healing, peri-implantitis induction was performed for another 3 months. After peri-implantitis defects were formed in both models, regenerative therapy was performed in both models. RESULTS: After 3 months in the immediate model and 9 months in the conventional model, similarly shaped horizontal bone defects (wide and craterlike) were observed. However, buccal bone defects were deeply formed in the immediate model compared with the conventional model (6.02 ± 1.20 and 4.34 ± 0.86 mm, respectively; P = 0.009), but the amounts of bone regeneration were not significantly different between the models (P = 0.107). On the lingual side, re-osseointegration was significantly greater in the conventional model than in the immediate model (0.72 ± 0.50 and 1.77 ± 0.87 mm, respectively; P = 0.009), although lingual bone defects were not significantly different between the models (P = 0.248). CONCLUSIONS: Although the immediate peri-implantitis model is challenging for regeneration, it may be able to replace the conventional model to study regenerative peri-implantitis treatment due to its short experimental time and similar defect configuration.

Nerve Growth Factor Expression and Its Receptors TrkA and p75NTR in Peri-Implantitis Lesions.

BACKGROUND: Nerve growth factor (NGF) can, through its receptors TrkA and p75NTR, convey signals for cell survival or cell differentiation. These proteins are also involved in inflammation and in bone resorption. The aim of this study is to evaluate, for the first time, the expression of NGF and its receptors TrkA and p75NTR in peri-implantitis lesions. MATERIALS AND METHODS: Fifteen biopsy specimens from patients with chronic peri-implantitis and 4 of healthy oral mucosa were immunostained with antibodies against NGF, TrkA, and p75NTR. The staining intensity and percentage of stained cells were semi-quantitatively evaluated and results were compared between the 2 groups. RESULTS: In the peri-implant pocket epithelium and gingival epithelium, NGF and TrkA expressions were similar to the healthy oral mucosa, however, a decreased expression of p75NTR was observed. In all cases, more than 75% of the inflammatory cells stained positively for NGF and TrkA, and p75NTR was negatively expressed. CONCLUSION: The intense expression of NGF and TrkA in the inflammatory cell infiltrate associated with decreased expression of p75NTR in both gingival and pocket epithelium suggests that these proteins may have a role in peri-implantitis lesions.

Group D. Initiator paper. Implants--peri-implant (hard and soft tissue) interactions in health and disease: the impact of explosion of implant manufacturers.

1. The best-documented implants have a threaded solid screw-type design and are manufactured from commercially pure (grade IV) titanium. There is good evidence to support implants ≥ 6 mm in length, and ≥ 3 mm in diameter. 2. Integrity of the seal between the abutment and the implant is important for several reasons, including minimization of mechanical and biological complications and maintaining marginal bone levels. Although the ideal design features of the implant-abutment connection have not been determined, an internal connection, micro-grooves at the implant collar, and horizontal offset of the implant-abutment junction (platform switch) appear to impart favorable properties. 3. Implants with moderately rough implant surfaces provide advantages over machined surfaces in terms of the speed and extent of osseointegration. While the favorable performances of both minimally and moderately rough surfaces are supported by long-term data, moderately rough surfaces provide superior outcomes in compromised sites, such as the posterior maxilla. 4. Although plaque is critical in the progression of peri-implantitis, the disease has a multi-factorial aetiology, and may be influenced by poor integrity of the abutment/implant connection. Iatrogenic factors, such as the introduction of a foreign body. (e.g., cement) below the mucosal margin, can be important contributors. 5. Clinicians should exercise caution when using a particular implant system, ensuring that the implant design is appropriate and supported by scientific evidence. Central to this is access to and participation in quality education on the impact that implant characteristics can have on clinical outcomes. Caution should be exercised in utilizing non-genuine restorative componentry that may lead to a poor implant-abutment fit and subsequent technical and biological complications.

Antibacterial properties and regenerative potential of Sr2+ and Ce3+ doped fluorapatites; a potential solution for peri-implantitis.

Scaffolds and implants in orthopaedics and regenerative dentistry usually fail because of bacterial infections. A promising solution would be the development of biomaterials with both significant regenerative potential and enhanced antibacterial activity. Working towards this direction, fluorapatite was synthesised and doped with Sr2+ and Ce3+ ions in order to tailor its properties. After experiments with four common bacteria (i.e. E. Coli, S. Aureus, B. Subtilis, B. Cereus), it was found that the undoped and the Ce3+ doped fluorapatites present better antibacterial response than the Sr2+ doped material. The synthesised minerals were incorporated into chitosan scaffolds and tested with Dental Pulp Stem Cells (DPSCs) to check their regenerative potential. As was expected, the scaffolds containing Sr2+-doped fluorapatite, presented high osteoconductivity leading to the differentiation of the DPSCs into osteoblasts. Similar results were obtained for the Ce3+-doped material, since both the concentration of osteocalcin and the RUNX2 gene expression were considerably higher than that for the un-doped mineral. Overall, it was shown that doping with Ce3+ retains the good antibacterial profile of fluorapatite and enhances its regenerative potential, which makes it a promising option for dealing with conditions where healing of hard tissues is compromised by bacterial contamination.

Influence of Microtextured Implant Surfaces on Peri-implantitis and Its Treatment: A Preclinical Trial.

PURPOSE: The prevalence of peri-implantitis has increased significantly, forcing clinicians to search for ways to prevent it. Laser-microtextured surfaces promote soft tissue attachment and provide a tight seal around implants. Hence, the aim of this study was to examine the clinical, radiographic, and histologic features of ligature-induced peri-implantitis, as well as the effect of surgical treatment of these induced peri-implantitis lesions on laser-microtextured implants in a controlled animal model. MATERIALS AND METHODS: Six mini-pigs (three males/three females) received 6 implants each (3 resorbable blast textured [RBT] implants and 3 laser-microtextured [LM] implants) in mandibular premolar sites, for a total of 36 implants. Two groups were identified based on the time point of sample analysis. After osseointegration was achieved, metal wire ligatures were placed and left for 12 weeks. Group 1 samples were then obtained, and group 2 samples received rescue therapy following a guided bone regeneration (GBR) protocol. Sample collection in group 2 was completed 12 weeks after the samples were submerged and treated. All samples were analyzed histologically and measurements were taken. RESULTS: Four implants (three RBT, one LM) were lost at early time points because of implant instability. Interimplant distances and soft tissue thicknesses varied subtly between groups. More notable was the mean (± standard error of the mean) crestal bone loss (group 1: 1.860 ± 1.618 mm [LM] and 2.440 ± 2.691 mm [RBT]; group 2: 2.04 ± 1.613 mm [LM] and 3.00 ± 2.196 mm [RBT]) (P < .05), as demonstrated by a paired t test. Histologic pocket depth was also greater at RBT sites than at LM sites (4.448 ± 2.839 mm and 4.121 ± 2.251 mm, respectively, in group 1; and 3.537 ± 2.719 mm and 2.339 ± 1.852 mm, respectively [P < .005] in group 2). CONCLUSION: LM implants had less crestal bone loss and shallower histologic pocket depth compared with their RBT counterparts. Also, LM implants had higher bone fill when a rescue therapy (GBR) was performed.

Biology of teeth and implants: The external environment, biology of structures, and clinical aspects.

For the past several thousand years, until development of the titanium dental implant, only a few missing teeth were replaced successfully in a very small number of individuals. Nowadays, placement of dental implants has become sufficiently commonplace that there is a need to interchange information between what we know about periodontal health and disease and what we know about health and disease involving dental implants. This review discusses the similarities and differences between teeth and dental implants with regards to anatomy, biology, physiology, and pathologic processes. The concept of biologic width is discussed in the context of interaction of periodontal and peri-implant tissues with microbial products produced by periodontal biofilms. The periodontal microbiome is discussed as networks of organisms interacting not only with periodontal and peri-implant tissues, but also with each other as networks of competing organisms. Overall, the transfer of biologic knowledge from what we know about peri-implantitis and what we know about periodontitis should help to develop new directions for biologic understanding about both health and disease of teeth and dental implants.

Biology of teeth and implants: Host factors - pathology, regeneration, and the role of stem cells.

In chronic periodontitis and peri-implantitis, cells of the innate and adaptive immune systems are involved directly in the lesions within the tissues of the patient. Absence of a periodontal ligament around implants does not prevent a biologic process similar to that of periodontitis from affecting osseointegration. Our first focus is on factors in the biology of individuals that are responsible for the susceptibility of such individuals to chronic periodontitis and to peri-implantitis. Genetic factors are of significant importance in susceptibility to these diseases. Genetic factors of the host affect the composition of the oral microbiome in the same manner that they influence other microbiomes, such as those of the intestines and of the lungs. Our second focus is on the central role of stem cells in tissue regeneration, in the functioning of innate and adaptive immune systems, and in metabolism of bone. Epithelial cell rests of Malassez (ERM) are stem cells of epithelial origin that maintain the periodontal ligament as well as the cementum and alveolar bone associated with the ligament. The tissue niche within which ERM are found extends into the supracrestal areas of collagen fiber-containing tissues of the gingivae above the bony alveolar crest. Maintenance and regeneration of all periodontal tissues involves the activity of a variety of stem cells. The success of dental implants indicates that important groups of stem cells in the periodontium are active to enable that biologic success. Successful replantation of avulsed teeth and auto-transplantation of teeth is comparable to placing dental implants, and so must also involve periodontal stem cells. Biology of teeth and biology of implants represents the biology of the various stem cells that inhabit specialized niches within the periodontal tissues. Diverse biologic processes must function together successfully to maintain periodontal health. Osseointegration of dental implants does not involve formation of cementum or collagen fibers inserted into cementum - indicating that some stem cells are not active around dental implants or their niches are not available. Investigation of these similarities and differences between teeth and implants will help to develop a better understanding of the biology and physiologic functioning of the periodontium.

Prevalence and Mechanisms of Peri-implant Diseases.

The aim of the present critical review is to summarize recent evidence on the prevalence of peri-implant diseases and their similarities and differences with periodontal diseases with a focus on their pathogenetic mechanisms. Reports on the extent and severity of peri-implant diseases are influenced by different case definitions. The prevalence of peri-implant diseases is reported at the subject or implant level and affected by the type of population samples analyzed (e.g., randomly selected population samples or convenience samples). The outcomes of studies on animals and humans indicate that experimental biofilm accumulation leads to a higher frequency of bleeding sites around implants as compared with teeth. Despite the proof of principle that experimentally induced mucositis may be reversible, early diagnosis and management of naturally occurring peri-implant mucositis are clinically relevant. Tissue destruction at experimental peri-implantitis sites is faster and more extensive when compared with that at experimental periodontitis sites. Although human periodontitis and peri-implantitis lesions share similarities with respect to etiology and clinical features, they represent distinct entities from a histopathologic point of view. To avoid implant loss, patients diagnosed with peri-implantitis should be treated without delay.

Can Periimplantitis Be Treated?

Over the past few decades, dental implants have been found to have high predictability and survival rates because of improvements in knowledge, clinical expertise, and implant designs. As such, dental implants are frequently integrated in the clinical management of fully or partially edentulous patients. It is prudent to realize that despite the high early survival rates, dental implants do have their fair share of long-term esthetic, biological, and mechanical complications. Therefore, this paper aims to review the current evidence on the management of peri-implant diseases in an attempt to answer the following question: Can periimplantitis be treated?

Full-mouth scaling and root planing combined with azithromycin to treat peri-implantitis.

BACKGROUND: Full-mouth scaling and root planing combined with azithromycin is clinically and bacteriologically effective for the treatment of chronic periodontitis. This study aimed to investigate the clinical and bacteriological effects of this combination treatment in patients with peri-implantitis. METHODS: Twenty adult patients with both chronic periodontitis and peri-implantitis were randomly divided into two groups (10: test, 10: control). All patients underwent full-mouth scaling and root planing but the test group received azithromycin for 3 days before the procedure. The probing depth, bleeding on probing, and the gingival index were assessed clinically. Bacterial samples were obtained before treatment at 1 week and 1, 3, 6, 9 and 12 months after treatment. Quantitative and qualitative analyses were performed using the polymerase chain reaction Invader method. RESULTS: All clinical parameters showed better improvement in both periodontitis and peri-implantitis in the test group. Periodontal bacteria were more effectively reduced in the test group, but gradually increased around implants 6 months after treatment and natural teeth 9 months after treatment. CONCLUSIONS: Full-mouth scaling and root planing combined with azithromycin was temporarily useful for the treatment of peri-implantitis. Clinical improvements were maintained for about 9 months but periodontal bacteria increased again 6 months after treatment.

Peri-implantitis. Part 2: Prevention and maintenance of peri-implant health.

The prevention of any disease process should be the cornerstone of any healthcare provision. This ethos is well established in dentistry with plaque associated disease such as periodontitis and caries but is at the current time less developed for peri-implantitis. The current review identities potential modifiable and non-modifiable risk factors for per-implantitis development and details strategies for the prevention of the disease. These include poor oral hygiene, previous history of periodontitis, smoking, genetic factors, occlusal overload and foreign body reactions. Local factors include soft tissue and bone quality, implant positioning, restoration design and the implant-abutment interface. An implant maintenance protocol is proposed and a schematic for maintenance visits is also detailed.

Peri-implantitis. Part 1: Scope of the problem.

Peri-implantitis is a relatively new disease process that results in gingival inflammation and bone loss around implants. The associated co-morbidities are significant due to the relative financial and biological costs of implant provision. At the current time there is a lack of consensus on the exact aetiology and subsequent pathological process, although this is largely thought to be infective in nature. Unfortunately, due to the relatively new nature of this problem, evidence is continually emerging on diagnosis, prevention, prevalence and incidence. This first part of three reviews will discuss these points and will act as an introduction to part two on prevention and part three on management of this now significant dental pathology.

Peri-implantitis versus periodontitis: functional differences indicated by transcriptome profiling.

BACKGROUND: Periodontitis and Periimplantitis are oftentimes discussed as one entity, which is reflected by therapeutical as well as by scientific approaches. It is unclear, to which extent the similarity of the clinical characteristics is attributed to similarities in the underlying disease mechanisms. PURPOSE: The main objective of the study is to display if or how different periimplantitis and periodontitis are on the mRNA level, representing a high-resolution map of disease-associated events. MATERIALS AND METHODS: Aiming to describe the pathophysiological mechanisms in vivo, primary gingival tissue from 7 periimplantitis patients, 7 periodontitis patients and 8 healthy controls was employed in order to generate genome wide transcriptome profiles. RESULTS: On the basis of quantitative transcriptome analysis, we could show that periimplantitis and periodontitis exhibit significantly different mRNA signatures. Additionally we present a disease associated mRNA profile, which displays potential periimplantitis disease mechanisms. A gene ontology analysis revealed various pathways, supporting the hypothesis of periimplantitis being a complex inflammatory disorder with a unique pathophysiology. While in periimplantitis tissue the regulation of transcripts related to innate immune responses and defense responses were dominating, in periodontitis tissues bacterial response systems prevailed. CONCLUSIONS: Taken together, our results suggest considering periimplantitis and periodontitis as disease entities with shared as well as with distinct features, which should be reflected on the therapeutical as well as on the scientific level.

Biomechanics and peri-implantitis: The effect of a subcrestal wing-thread to decrease alveolar crestal bone strain. theory, finite element analysis, and clinical application.

PURPOSE: This study used finite element analysis and a clinical case example to test the hypothesis that a wing-thread placed 4 mm below the top of an implant would decrease crestal bone loss in function. MATERIALS AND METHODS: Finite element analysis was used to compare standard and wing-thread implants subjected to axial and off-axis forces based on the hypothesis that decreasing bone strain at the alveolar crestal margin improves peri-implant bone stability. A clinical case example of the wing-thread implant was followed for 30 months. RESULTS: Stress concentration was diminished at the crest when a wing-thread was used compared to a standard implant body. Ninety-degree lateral forces were diminished by a factor of 10 in the wing-thread implant. A patient followed for 30 months showed stable bone levels around the wing-thread implants. CONCLUSION: The wing-thread hypothesis appears to have some support for increasing bone stability based on finite element analysis and early clinical results.

Bone loss at implant with titanium abutments coated by soda lime glass containing silver nanoparticles: a histological study in the dog.

The aim of the present study was to evaluate bone loss at implants connected to abutments coated with a soda-lime glass containing silver nanoparticles, subjected to experimental peri-implantitis. Also the aging and erosion of the coating in mouth was studied. Five beagle dogs were used in the experiments. Three implants were placed in each mandible quadrant: in 2 of them, Glass/n-Ag coated abutments were connected to implant platform, 1 was covered with a Ti-mechanized abutment. Experimental peri-implantitis was induced in all implants after the submarginal placement of cotton ligatures, and three months after animals were euthanatized. Thickness and morphology of coating was studied in abutment cross-sections by SEM. Histology and histo-morphometric studies were carried on in undecalfied ground slides. After the induced peri-implantitis: 1.The abutment coating shown losing of thickness and cracking. 2. The histometry showed a significant less bone loss in the implants with glass/n-Ag coated abutments. A more symmetric cone of bone resorption was observed in the coated group. There were no significant differences in the peri-implantitis histological characteristics between both groups of implants. Within the limits of this in-vivo study, it could be affirmed that abutments coated with biocide soda-lime-glass-silver nanoparticles can reduce bone loss in experimental peri-implantitis. This achievement makes this coating a suggestive material to control peri-implantitis development and progression.

Comparison of the levels of tumor necrosis factor-α and interleukin-17 in gingival crevicular fluid of patients with peri-implantitis and a control group with healthy implants.

Peri-implantitis is a multi-factorial disease involving peri-implant tissues and resulting in therapeutic failure. Inflammatory mediators and cytokines in the Gingival Crevicular Fluid (GCF) have pivotal roles in the disease pathogenesis and could be used for disease monitoring. Therefore, the present study was conducted to compare the GCF levels of TNF-α and IL-17 between patients with peri-implantitis and healthy implants.In this case-control study, 24 patients with peri-implantitis and 18 individuals with healthy implants referring to faculty of dentistry in Tehran University of Medical Sciences were selected. GCF was collected by paper cons number 30. Samples were preserved in PBS -70ºC. TNF-α and IL-17 levels in GCF were determined by ELISA method. Data were analyzed by SPSS software version 13, using descriptive indices and independent t tests.Mean probing depth in peri-implantitis and control groups were 6.2 ± 1.1 and 3.7 ± 1.6 mm respectively. Mean level of IL-17 in patients with peri-implantitis was significantly more than the control group (19.8 ± 16.0 versus 9.3 ± 8.4 pg per site in 40 seconds, p=0.016). Also, mean level of TNF-α in patients with peri-implantitis was more than control group (39.0 ± 3.9 versus 14.5 ± 9.0 pg per site in 40 seconds, p =0.000).The significant higher levels of TNF-α and IL-17 in patients with peri-implantitis compared to control group indicated the pivotal role of these cytokines in peri-implantitis and could be suggested as diagnostic markers and in future possibly for immunomodulatory treatments.

Extent and location of bone loss at dental implants in patients with peri-implantitis.

Peri-implantitis is an infectious disease, which leads to loss of supporting bone around dental implants. To evaluate the extent and location of bone loss, 43 patients with peri-implantitis were examined. The bone loss was clinically measured at the time of dental surgery. Data revealed that 25% of subjects had bone loss associated with all their implants although the majority of the subjects had fewer than 50% of their implants affected by bone loss. A total number of 264 implants were examined and 131 of those had peri-implantitis associated bone loss. The pattern of bone loss at implants varied between and within subjects and location in the jaws. The highest proportion of implants with peri-implantitis was found in the upper jaw and within this group, at implants located in the incisor area of the upper jaw; the lowest was the canine area of the lower jaw. The highest proportion of implants that lost ≥ 2/3 of their bone support was found in the incisor area of the maxilla. We concluded that in the presence of peri-implant inflammation, bone quantity and characteristics may influence the progression of peri-implantitis bone loss at dental implants. We hypothesize that the ability of the bone to withstand occlusal forces will be altered as consequence of the loss of bone at the neck of the implants. To achieve an understanding of the local degradation of bone due to peri-implantitis, we need to analyze the microstructure of the bone as well the cellular biology of the peri-implant inflammation.