The Guided Bone Regeneration (GBR) treatment concept advocates that regeneration of osseous defects is predictably attainable via the application of occlusive membranes, which mechanically exclude ...non‐osteogenic cell populations from the surrounding soft tissues, thereby allowing osteogenic cell populations originating from the parent bone to inhabit the osseous wound. The present review discusses the evolution of the GBR biological rationale and therapeutic concept over the last two decades. Further, an overview of the GBR research history is provided with specific focus on the evidence available on its effectiveness and predictability in promoting the regeneration of critical size cranio‐maxillo‐facial defects, the neo‐osteogenesis potential and the reconstruction of atrophic alveolar ridges before, or in conjunction with, the placement of dental implants. The authors conclude that future research should focus on (a) the investigation of the molecular mechanisms underlying the wound healing process following GBR application; (b) the identification of site and patient related factors which impact on the effectiveness and predictability of GBR therapy and (c) the evaluation of the pathophysiology of the GBR healing process in the presence of systemic conditions potentially affecting the skeletal system.
To cite this article:
Retzepi M, Donos N. Guided Bone Regeneration: biological principle and therapeutic applications. Clin. Oral Impl. Res. 21, 2010; 567–576. doi: 10.1111/j.1600‐0501.2010.01922.x
Objectives
The task of this working group was to analyze biological, technical and aesthetic complications of single crowns on implants and fixed dental prostheses with or without cantilevers on ...implants over 5 years or more. In addition, the group analyzed economic aspects on such implant treatment.
Materials and methods
A systematic search of the relevant literature was conducted and critically reviewed. Four manuscripts were presented to cover the topics.
Results
The consensus statements prepared by the group and later accepted at the plenary session as well as suggestions for future research are presented in this article. The four reviews by Jung et al., Pjetursson et al., Romeo & Storelli and Scheuber et al. are printed separately and present detailed analyses of the research topics.
: Diabetes mellitus and, in particular, type 1 diabetes has been associated with impaired osseous wound healing properties. The scope of the present review is to discuss the clinical evidence ...supporting a higher rate of complications during fracture healing in diabetic patients and the histological evidence indicating impaired potential for intramembranous and endochondral ossification in the presence of uncontrolled experimental diabetes. The article further provides a synthesis of our current understanding of the plausible molecular mechanisms underlying the diabetic bone healing pathophysiology and of the role of insulin treatment in promoting osseous healing in the diabetic status.
To cite this article:
Retzepi M, Donos N. The effect of diabetes mellitus on osseous healing. Clin. Oral Impl. Res. 21, 2010; 673–681. doi: 10.1111/j.1600‐0501.2010.01923.x
Periodontal infections have been associated with a state of chronic inflammation. To ascertain whether severe periodontitis and its treatment are associated with oxidative stress, we recruited 145 ...cases (periodontitis) and 56 controls in a case-control study. A further pilot intervention study of 14 cases (periodontal therapy) was performed. Blood samples were taken at baseline (case-control) and 1, 3, 5, 7, and 30 days after treatment (intervention). Diacron-reactive oxygen metabolites (D-ROM), anti-oxidant potential, C-reactive protein (CRP), interleukin-6, and lipid profiles were determined with high-sensitivity assays in serum. Patients with severe periodontitis exhibited higher D-ROM levels (P < 0.001) and lower total anti-oxidant capacity (P < 0.001) compared with healthy control individuals. These findings were independent of age, gender, smoking habits, ethnicity, and standard lipids differences. D-ROM levels were positively correlated with CRP (R = 0.4, P < 0.001) and clinical periodontal parameters (R = 0.20, P < 0.05). Acute increases of D-ROM (P < 0.01) were observed following periodontal therapy. Analysis of these data suggests a positive association between severe periodontitis and oxidative stress.
Background
It is now generally accepted that the response to a particular signal, such as the surgical trauma following implant placement, is not the result of a single linear signalling pathway, but ...rather reflects pathway integration, which can occur at multiple levels. Although it is well documented that both SLA and SLActive surfaces are able to promote bone formation and osseointegration, it is still unclear which are the key signalling pathways involved and how surface hydrophilicity/hydrophobicity might affect pathway integration.
Objective
To combine gene and protein data from in vivo studies applying titanium hydrophobic (Sandblasting, Large‐grit, Acid‐etching, SLA) and hydrophilic (SLActive) surfaces to understand the molecular mechanisms responsible for the pro‐osteogenic properties of these surfaces.
Methods
The Kyoto Encyclopedia of Genes and Genomes (KEGG®) pathway database and the Ingenuity® Pathway Analysis (IPA®) software were applied to the genomic and proteomic data of previous in vivo studies applying SLA and SLActive surfaces, with the specific aim to focus on bone formation‐related signalling pathways. While gene data were derived from a human study on osseointegration, protein data originated from a preclinical study in rabbits. Data were available for the 4, 7 and 14 days of healing periods.
Results
Both genomic and proteomic data showed that the osteogenesis process takes place mainly at 7 and 14 days of healing on both SLA and SLActive surfaces. Surface hydrophilicity enhances bone formation at multiple levels, by directly promoting an earlier expression of pathways involved in cell proliferation and osteoblast precursor differentiation (eg, mitogen‐activated protein kinase, phosphoinositide‐3 kinase‐AKT, Wnt, Notch, transforming growth factor‐β), but also by positively regulating angiogenesis, bone mineralization and bone remodelling.
Conclusion
This study combined, for the first time, different ‘omics’ outputs to get new insights on the molecular mechanisms behind the influence of surface hydrophilicity on osseointegration/bone formation. Specific signalling pathways, such as Wnt, vascular endothelial growth factor and mitogen‐activated protein kinase, were identified as differentially modulated by titanium surface hydrophilicity both at a genomic and proteomic level. These findings may be used in the future to monitor/predict the bone formation/osseointegration process, or as a screening tool towards the manufacture of new pro‐osteogenic implant surfaces. In order to take into account the full complexity and interplay of cell signalling during bone formation, powerful bioinformatics tools integrating different ‘omics’ data and predicting signalling pathways trends should be applied by future studies.
Osteoporosis is one of the most common skeletal disorders affecting a significant percentage of people worldwide. Research data suggested that systemic diseases such as osteoporosis could act as risk ...factors for osseointegration, jeopardizing the healing process and thus the predictability of dental implant success on compromised patients. It is well accepted that preclinical studies in animal models reproducing the osteoporotic condition are one of the most important stages in the research of new biomaterials and therapeutic modalities. The aim of this systematic review was to investigate whether osteoporosis compromises dental implant osseointegration in experimental osteoporotic‐like conditions. A 3‐stage systematic literature research was conducted in MEDLINE via OVID and EMBASE up to and including March 2017. Experimental studies reporting on dental implant osseointegration on different osteoporotic animal models were assessed. The studies had to report on the percentage of bone‐to‐implant contact (%BIC) as the primary outcome. ARRIVE guidelines for reporting on animal research were applied to evaluate the methodological quality and risk of bias of the studies. Fifty‐seven studies met the inclusion criteria and were assessed qualitatively. The most adopted animal model was the rat. A variability of %BIC values was observed, ranging from 30% to 99% and from 26% to 94% for the healthy and osteoporotic group, respectively. The great majority (47) of the included studies concluded that estrogen deficiency significantly affects BIC values, 9 studies stated that it was not possible to observe statistical differences in BIC between ovariectomized and healthy groups and 1 study did not provide a comparison between the healthy and osteoporotic group. Owing to the great heterogeneity in implant surface, study design, observation time‐points, site of implant placement and reported outcomes, a meta‐analysis could not be performed. An overall high risk of bias was observed, owing to the limited information on animal housing and husbandry, baseline characteristics and health status, ethical statement and allocation to the experimental groups provided. Although the available studies seem to suggest a lower osseointegration in osteoporotic‐like conditions, no robust conclusions can be drawn due to the great heterogeneity and overall low quality of the available studies. Future studies with emphasis on minimizing the possible sources of bias and evaluating osseointegration of dental implants placed into jawbones instead of long bones are warranted.
Oral Diseases (2012) 18, 236–243
Interleukin‐6 (IL‐6) is a pleomorphic cytokine involved in a number of physiologic and pathologic processes including response to trauma and infection and development ...and progression of inflammation and malignancy. IL‐6 is emerging as an important mediator and novel therapeutic target for chronic inflammatory diseases and cancer. The present study reviews the available evidence regarding the association between IL‐6 and a range of oral diseases including infections (periodontal disease and endodontic infections), immunologically mediated disorders (oral lichen planus and Sjögren’s syndrome) and malignancy (oral cancer and precancer). The role of common genetic variants of IL‐6 in determining individual susceptibility to certain oral diseases, as well as novel therapeutic strategies based on IL‐6 inhibition are also discussed.
Increased life expectancy and broader restorative dental treatment alternatives for missing teeth have resulted in an increasing request of bone regeneration/augmentation procedures not only in ...healthy patients, but also in elderly and medically compromised ones. This is also combined with a growing demand for short implant loading protocols and for optimal aesthetic results. In order to meet these new dental needs, personalized treatment strategies tailored on each individual's characteristics and healing profile are warranted.
Omics technologies are emerging as powerful tools to uncover molecules and signalling pathways involved in bone formation and osseointegration and to investigate differences in the molecular mechanisms between health and systemic diseases that could be targeted by future therapies.
This review critically appraises the available knowledge on the application of omics technologies in the field of bone regeneration and osseointegration and explores their potential use for personalized medicine in the dento-maxillo-facial field.
The use of omics in personalising dental maxillo-facial treatments emerges as a desirable diagnostic and treatment strategy. Omics represent, in fact, powerful tools not only to shade light on the cascade of events taking place during bone formation/osseointegration, but also to identify specific signalling pathways and molecules that can be targeted by future therapies with the aim to enhance clinical outcomes in patients with compromised healing conditions.
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•Need for personalised treatment strategies in the dental maxilla-facial field•Disease-specific molecules/impaired signalling pathways identified with omics technologies•Omics characterization of implant surfaces to enhance bone formation
Several systemic diseases (and relative medications) have been reported to impair or in some cases complicate dental implant surgery. In broader terms, when dealing with patients suffering from ...systemic diseases, the monitoring of the medical condition and of the related post-operative complications is of great importance in order to avoid risks which could jeopardise the health of the patient. In this review, the available evidence on implant survival/success, as well as relevant surgical recommendations in patients affected by systemic diseases, are evaluated and when possible, practical suggestions for the clinician are provided.
Different quantitative and qualitative indices calculated on oral panoramic radiographs have been proposed as useful tools to screen for reduced skeletal bone mineral density (BMD). Our aim was to ...systematically review the literature on linear and qualitative panoramic measures and to assess the accuracy of these indices by performing a meta-analysis of their sensitivity and specificity. The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement was followed. Fifty studies were included in the qualitative appraisal and 19 were considered for meta-analysis. The methodological quality of the retrieved studies, assessed with the QUADAS-2 tool, was on average low. Three indices were reported by most of the studies: mandibular cortical width, panoramic mandibular index, and the Klemetti index. Mandibular cortical width presented with a better accuracy in excluding osteopenia/osteoporosis (specificity), since patients with a cortical width more than 4 mm had a normal BMD in 90% of the cases. Almost all studies used a cutoff of 0.3 for the panoramic mandibular index, resulting in an estimated sensitivity and specificity in detecting reduced BMD, respectively, of 0.723 (SE 0.160; 95% confidence interval CI, 0.352–0.926) and 0.733 (SE 0.066; 95% CI, 0.587–0.841). The presence of any kind of mandibular cortical erosion gave an estimated sensitivity and specificity in detecting reduced BMD, respectively, of 0.789 (SE 0.031; 95% CI, 0.721–0.843) and 0.562 (SE 0.047; 95% CI, 0.47–0.651) and a sensitivity and specificity in detecting osteoporosis, respectively, of 0.806 (SE 0.105; 95% CI, 0.528–0.9200) and 0.643 (SE 0.109; 95% CI, 0.417–0.820). The mandibular cortical width, panoramic mandibular index, and Klemetti index are overall useful tools that potentially could be used by dentists to screen for low BMD. Their limitations are mainly related to the experience/agreement between different operators and the different image quality and magnification of the panoramic radiographs.
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