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Showing papers in "Periodontology 2000 in 2015"


Journal ArticleDOI
TL;DR: This volume of Periodontology 2000 tries to draw these complex new learnings into a contemporary model of disease pathogenesis, in which inflammation and dysbiosis impact upon whether the outcome is driven toward acute resolution and stability, chronic resolution and repair, or failed resolution and ongoing periodontal tissue destruction.
Abstract: The past decade of basic research in periodontology has driven radical changes in our understanding and perceptions of the pathogenic processes that drive periodontal tissue destruction. The core elements of the classical model of disease pathogenesis, developed by Page & Kornman in 1997, remain pertinent today; however, our understanding of the dynamic interactions between the various microbial and host factors has changed significantly. The molecular era has unraveled aspects of genetics, epigenetics, lifestyle and environmental factors that, in combination, influence biofilm composition and the host's inflammatory immune response, creating a heterogenic biological phenotype that we label as 'periodontitis'. In this volume of Periodontology 2000, experts in their respective fields discuss these emerging concepts, such as a health-promoting biofilm being essential for periodontal stability, involving a true symbiosis between resident microbial species and each other and also with the host response to that biofilm. Rather like the gut microbiome, changes in the local environment, which may include inflammatory response mediators or viruses, conspire to drive dysbiosis and create a biofilm that supports pathogenic species capable of propagating disease. The host response is now recognized as the major contributor to periodontal tissue damage in what becomes a dysfunctional, poorly targeted and nonresolving inflammation that only serves to nourish and sustain the dysbiosis. The role of epithelial cells in signaling to the immune system is becoming clearer, as is the role of dendritic cells as transporters of periodontal pathogens to distant sites within the body, namely metastatic infection. The involvement of nontraditional immune cells, such as natural killer cells, is being recognized, and the simple balance between T-helper 1- and T-helper 2-type T-cell populations has become less clear with the emergence of T-regulatory cells, T-helper 17 cells and follicular helper cells. The dominance of the neutrophil has emerged, not only as a potential destructor when poorly regulated but as an equally unpredictable effector cell for specific B-cell immunity. The latter has emerged, in part, from the realization that neutrophils live for 5.4 days in the circulation, rather than for 24 h, and are also schizophrenic in nature, being powerful synthesizers of proinflammatory cytokines but also responding to prostaglandin signals to trigger a switch to a pro-resolving phenotype that appears capable of regenerating the structure and function of healthy tissue. Key to these outcomes are the molecular signaling pathways that dominate at any one time, but even these are influenced by microRNAs capable of 'silencing' certain inflammatory genes. This volume of Periodontology 2000 tries to draw these complex new learnings into a contemporary model of disease pathogenesis, in which inflammation and dysbiosis impact upon whether the outcome is driven toward acute resolution and stability, chronic resolution and repair, or failed resolution and ongoing periodontal tissue destruction.

377 citations


Journal ArticleDOI
TL;DR: The outcomes of laser therapy in soft-tissue management, periodontal nonsurgical and surgical treatment, osseous surgery and peri-implant treatment are discussed, focusing on postoperative wound healing ofperiodontal and pero-IMplant tissues.
Abstract: Laser irradiation has numerous favorable characteristics, such as ablation or vaporization, hemostasis, biostimulation (photobiomodulation) and microbial inhibition and destruction, which induce various beneficial therapeutic effects and biological responses. Therefore, the use of lasers is considered effective and suitable for treating a variety of inflammatory and infectious oral conditions. The CO2 , neodymium-doped yttrium-aluminium-garnet (Nd:YAG) and diode lasers have mainly been used for periodontal soft-tissue management. With development of the erbium-doped yttrium-aluminium-garnet (Er:YAG) and erbium, chromium-doped yttrium-scandium-gallium-garnet (Er,Cr:YSGG) lasers, which can be applied not only on soft tissues but also on dental hard tissues, the application of lasers dramatically expanded from periodontal soft-tissue management to hard-tissue treatment. Currently, various periodontal tissues (such as gingiva, tooth roots and bone tissue), as well as titanium implant surfaces, can be treated with lasers, and a variety of dental laser systems are being employed for the management of periodontal and peri-implant diseases. In periodontics, mechanical therapy has conventionally been the mainstream of treatment; however, complete bacterial eradication and/or optimal wound healing may not be necessarily achieved with conventional mechanical therapy alone. Consequently, in addition to chemotherapy consisting of antibiotics and anti-inflammatory agents, phototherapy using lasers and light-emitting diodes has been gradually integrated with mechanical therapy to enhance subsequent wound healing by achieving thorough debridement, decontamination and tissue stimulation. With increasing evidence of benefits, therapies with low- and high-level lasers play an important role in wound healing/tissue regeneration in the treatment of periodontal and peri-implant diseases. This article discusses the outcomes of laser therapy in soft-tissue management, periodontal nonsurgical and surgical treatment, osseous surgery and peri-implant treatment, focusing on postoperative wound healing of periodontal and peri-implant tissues, based on scientific evidence from currently available basic and clinical studies, as well as on case reports.

262 citations


Journal ArticleDOI
TL;DR: In conclusion, tooth extraction, once a simple and straightforward surgical procedure, should be performed in the knowledge that ridge reduction will follow and that further clinical steps should be considered to compensate for this, when considering future options for tooth replacement.
Abstract: Tooth extraction induces a series of complex and integrated local changes within the investing hard and soft tissues. These local alterations arise in order to close the socket wound and to restore tissue homeostasis, and are referred to as '"socket healing". The aims of the present report were twofold: first, to describe the socket-healing process; and, second, to discuss what can be learned from the temporal sequence of healing events, in order to improve treatment outcomes. The socket-healing process may be divided into three sequential, and frequently overlapping, phases: inflammatory; proliferative; and modeling/remodeling. Several clinical and experimental studies have demonstrated that the socket-healing process promotes up to 50% reduction of the original ridge width, greater bone resorption at the buccal aspect than at the lingual/palatal counterpart and a larger amount of alveolar bone reduction in the molar region. In conclusion, tooth extraction, once a simple and straightforward surgical procedure, should be performed in the knowledge that ridge reduction will follow and that further clinical steps should be considered to compensate for this, when considering future options for tooth replacement.

262 citations


Journal ArticleDOI
TL;DR: In addition to promoting neutrophilic inflammation, interleukin-17 has potent pro-osteoclastogenic effects that are likely to contribute to the pathogenesis of periodontitis, rheumatoid arthritis and other diseases involving bone immunopathology.
Abstract: Interleukin-17 (also known as interleukin-17A) is a key cytokine that links T-cell activation to neutrophil mobilization and activation. As such, interleukin-17 can mediate protective innate immunity to pathogens or contribute to the pathogenesis of inflammatory diseases, such as psoriasis and rheumatoid arthritis. This review summarizes the basic biology of interleukin-17 and discusses its emerging role in periodontal disease. The current burden of evidence from human and animal model studies suggests that the net effect of interleukin-17 signaling promotes disease development. In addition to promoting neutrophilic inflammation, interleukin-17 has potent pro-osteoclastogenic effects that are likely to contribute to the pathogenesis of periodontitis, rheumatoid arthritis and other diseases involving bone immunopathology. Systemic treatments with anti-interleukin-17 biologics have shown promising results in clinical trials for psoriasis and rheumatoid arthritis; however, their impact on the highly prevalent periodontal disease has not been investigated or reported. Future clinical trials, preferably using locally administered interleukin-17 blockers, are required to implicate conclusivelyinterleukin-17 in periodontitis and, more importantly, to establish an effective adjunctive treatment for this oral inflammatory disease.

246 citations


Journal ArticleDOI
TL;DR: Current knowledge in terms of the etiology, diagnosis, prognosis and surgical treatment of gingival recession is summarized to limit patient morbidity and improve the esthetic outcome.
Abstract: The aim of the present article is to summarize current knowledge in terms of the etiology, diagnosis, prognosis and surgical treatment of gingival recession. Whilst the main etiological factors (i.e. toothbrushing trauma and bacterial plaque) are well established, challenges still remain to be solved in the diagnostic, prognostic and classification processes of gingival recession, especially when the main reference parameter - the cemento-enamel junction - is no longer detectable on the affected tooth or when there is a slight loss of periodontal interdental attachment. Root coverage in single type gingival recession defects is a very predictable outcome following the use of various surgical techniques. The coronally advanced flap, with or without connective tissue grafting, is the technique of choice. The adjunctive use of connective tissue grafts improves the probability of achieving complete root coverage. Surgical coverage of multiple gingival recessions is also predictable with the coronally advanced flap and the coronally advanced flap plus the connective tissue graft, but no data are available indicating which, and how many, gingival recessions should be treated adjunctively with connective tissue grafting in order to limit patient morbidity and improve the esthetic outcome. None of the allograft materials currently available can be considered as a full substitute for the connective tissue graft, even if some recent results are encouraging. The need for future studies with patient-based outcomes (i.e. esthetics and morbidity) as primary objectives is emphasized in this review.

222 citations


Journal ArticleDOI
TL;DR: The results of the present systematic review indicate that periodontal regeneration in human intrabony defects can be achieved to a variable extent using a range of methods and materials.
Abstract: Intrabony periodontal defects are a frequent complication of periodontitis and, if left untreated, may negatively affect long-term tooth prognosis. The optimal outcome of treatment in intrabony defects is considered to be the absence of bleeding on probing, the presence of shallow pockets associated with periodontal regeneration (i.e. formation of new root cementum with functionally orientated inserting periodontal ligament fibers connected to new alveolar bone) and no soft-tissue recession. A plethora of different surgical techniques, often including implantation of various types of bone graft and/or bone substitutes, root surface demineralization, guided tissue regeneration, growth and differentiation factors, enamel matrix proteins or various combinations thereof, have been employed to achieve periodontal regeneration. Despite positive observations in animal models and successful outcomes reported for many of the available regenerative techniques and materials in patients, including histologic reports, robust information on the degree to which reported clinical improvements reflect true periodontal regeneration does not exist. Thus, the aim of this review was to summarize, in a systematic manner, the available histologic evidence on the effect of reconstructive periodontal surgery using various types of biomaterials to enhance periodontal wound healing/regeneration in human intrabony defects. In addition, the inherent problems associated with performing human histologic studies and in interpreting the results, as well as certain ethical considerations, are discussed. The results of the present systematic review indicate that periodontal regeneration in human intrabony defects can be achieved to a variable extent using a range of methods and materials. Periodontal regeneration has been observed following the use of a variety of bone grafts and substitutes, guided tissue regeneration, biological factors and combinations thereof. Combination approaches appear to provide the best outcomes, whilst implantation of alloplastic material alone demonstrated limited, to no, periodontal regeneration.

199 citations


Journal ArticleDOI
TL;DR: Clinicians should strongly advise smokers to enroll in cessation strategies, even temporarily, in order to improve the overall outcome and some of the reported deleterious effects of smoking on periodontal tissues have been reported to be reversible upon participation in smoking-cessation programs.
Abstract: This literature review provides an overview of the current scenario regarding the impact of smoking on the progression and treatment of periodontitis; clinical, microbiological and immunological data from studies from our and other groups are presented. In general, preclinical and clinical data are unanimous in demonstrating that smokers present increased susceptibility, greater severity and faster progression of periodontal disease compared with nonsmokers. The evidence further demonstrates that smokers lose more teeth and have a less favorable response to therapy than do nonsmokers. Although it is well established that smoking significantly impacts on the onset, progression and outcome of periodontal disease, the mechanisms involved remain unclear. More importantly, some of the reported deleterious effects of smoking on periodontal tissues have been reported to be reversible upon participation in smoking-cessation programs. Therefore, clinicians should strongly advise smokers to enroll in cessation strategies, even temporarily, in order to improve the overall outcome.

192 citations


Journal ArticleDOI
TL;DR: A strategy to optimize the clinical outcomes of periodontal regeneration is presented and the surgical design of the flap, the use of different regenerative materials and the application of appropriate passive sutures are discussed in this review.
Abstract: Evidence indicates that periodontal regeneration is an efficacious and predictable procedure for the treatment of isolated and multiple intrabony defects. Meta-analyses from systematic reviews indicate an added benefit, in terms of clinical attachment level gain, when demineralized freeze-dried bone allograft, barrier membranes and active biologic products/compounds are applied in addition to open flap debridement. On the other hand, a consistent amount of variability of the outcomes is evident among different studies and within the experimental population of each study. This variability is explained, at least in part, by different patient and defect characteristics. Patient-related factors include smoking habit, compliance with home oral hygiene and residual inflammation after cause-related therapy. Defect-associated factors include defect depth and radiographic angle, the number of residual bony walls, pocket depth and the degree of hypermobility. In addition, surgical-related variables, such as surgical skill, clinical experience and knowledge, and application of the different regenerative materials, have a significant impact on clinical outcomes. This paper presents a strategy to optimize the clinical outcomes of periodontal regeneration. The surgical design of the flap, the use of different regenerative materials and the application of appropriate passive sutures are discussed in this review along with the scientific foundations.

171 citations


Journal ArticleDOI
TL;DR: A new treatment concept in which natural pathways of resolution of periodontal inflammation can be used to limit systemic inflammation and promote healing and regeneration is discussed.
Abstract: Inflammation is a highly organized event impacting upon organs, tissues and biological systems Periodontal diseases are characterized by dysregulation or dysfunction of resolution pathways of inflammation that results in failure to heal and in a dominant chronic, progressive, destructive and predominantly unresolved inflammation The biological consequences of inflammatory processes may be independent of the etiological agents, such as trauma, microbial organisms and stress The impact of the inflammatory pathological process depends upon the tissues or organ system affected Whilst mediators are similar, there is tissue specificity for the inflammatory events It is plausible that inflammatory processes in one organ could directly lead to pathologies in another organ or tissue Communication between distant parts of the body and their inflammatory status is also mediated by common signaling mechanisms mediated via cells and soluble mediators This review focuses on periodontal inflammation, its systemic associations and advances in therapeutic approaches based on mediators acting through orchestration of natural pathways to resolution of inflammation We also discuss a new treatment concept in which natural pathways of resolution of periodontal inflammation can be used to limit systemic inflammation and promote healing and regeneration

157 citations


Journal ArticleDOI
TL;DR: This article endeavored to provide a 'state of the art' overview on the use of systemic antibiotics in the treatment of periodontitis, based on the most recent literature on the topic as well as on a compilation of data from studies conducted at the Center of Clinical Trials at Guarulhos University from 2002 to 2012.
Abstract: Despite the fact that several clinical studies have shown additional benefits when certain systemic antibiotics are used as adjuncts to periodontal treatment, clear guidelines for the use of these agents in the clinical practice are not yet available. Basic questions concerning the use of systemic antibiotics to treat periodontitis remain unanswered, such as: which drug(s) should be used; which patients would most benefit from treatment; which are the most effective protocols (i.e. doses and durations); and in which phase of the mechanical therapy should the drug(s) be administered? Although not all of those questions have been directly addressed by controlled randomized clinical trials, recent concepts related to the ecology of periodontal diseases, as well as the major advances in laboratory and clinical research methods that have occurred in the past decade, have significantly broadened our knowledge in this field. This article endeavored to provide a ‘state of the art’ overview on the use of systemic antibiotics in the treatment of periodontitis, based on the most recent literature on the topic as well as on a compilation of data from studies conducted at the Center of Clinical Trials at Guarulhos University (Sao Paulo, Brazil) from 2002 to 2012.

151 citations


Journal ArticleDOI
TL;DR: The oral epithelium is able to react to a variety of exogenous, possibly noxious influences and is suggested to be an enhancement of human papilloma virus infection by HIV-associated disruption of tight junctions.
Abstract: The oral epithelial barrier separates the host from the environment and provides the first line of defense against pathogens, exogenous substances and mechanical stress. It consists of underlying connective tissue and a stratified keratinized epithelium with a basement membrane, whose cells undergo terminal differentiation resulting in the formation of a mechanically resistant surface. Gingival keratinocytes are connected by various transmembrane proteins, such as tight junctions, adherens junctions and gap junctions, each of which has a specialized structure and specific functions. Periodontal pathogens are able to induce inflammatory responses that lead to attachment loss and periodontal destruction. A number of studies have demonstrated that the characteristics of pathogenic oral bacteria influence the expression and structural integrity of different cell-cell junctions. Tissue destruction can be mediated by host cells following stimulation with cytokines and bacterial products. Keratinocytes, the main cell type in gingival epithelial tissues, express a variety of proinflammatory cytokines and chemokines, including interleukin-1alpha, interleukin-1beta, interleukin-6, interleukin-8 and tumor necrosis factor-alpha. Furthermore, the inflammatory mediators that may be secreted by oral keratinocytes are vascular endothelial growth factor, prostaglandin E2 , interleukin-1 receptor antagonist and chemokine (C-C motif) ligand 2. The protein family of matrix metalloproteinases is able to degrade all types of extracellular matrix protein, and can process a number of bioactive molecules. Matrix metalloproteinase activities under inflammatory conditions are mostly deregulated and often increased, and those mainly relevant in periodontal disease are matrix metalloproteinases 1, 2, 3, 8, 9, 13 and 24. Viral infection may also influence the epithelial barrier. Studies show that the expression of HIV proteins in the mucosal epithelium is correlated with the disruption of epithelial tight junctions, suggesting a possible enhancement of human papilloma virus infection by HIV-associated disruption of tight junctions. Altered expression of matrix metalloproteinases was demonstrated in keratinocytes transformed with human papilloma virus-16 or papilloma virus-18,. To summarize, the oral epithelium is able to react to a variety of exogenous, possibly noxious influences.

Journal ArticleDOI
TL;DR: This review will examine the characteristics of cementum, its composition and the role of cementu components, especially the cementum protein-1, during the process of cementogenesis, and their potential usefulness for regeneration of the periodontal structures in a predictable therapeutic manner.
Abstract: Destruction of the periodontium is normally associated with periodontal disease, although many other factors, such as trauma, aging, infections, orthodontic tooth movement and systemic and genetic diseases, can contribute to this process Strategies (such as guided tissue regeneration) have been developed to guide and control regeneration using bioresorbable membranes and bone grafts Although effective to a certain point, these strategies have the problem that they are not predictable and do not completely restore the architecture of the original periodontium To achieve complete repair and regeneration it is necessary to recapitulate the developmental process with complete formation of cementum, bone and periodontal ligament fibers Detailed knowledge of the biology of cementum is key for understanding how the periodontium functions, identifying pathological issues and for developing successful therapies for repair and regeneration of damaged periodontal tissue It is the purpose of this review to focus on the role of cementum and its specific components in the formation, repair and regeneration of the periodontium As cementum is a matrix rich in growth factors that could influence the activities of various periodontal cell types, this review will examine the characteristics of cementum, its composition and the role of cementum components, especially the cementum protein-1, during the process of cementogenesis, and their potential usefulness for regeneration of the periodontal structures in a predictable therapeutic manner

Journal ArticleDOI
TL;DR: Polymicrobial interactions with the host in both health and disease is discussed, indicating that their host-associated polymicrobial communities, such as those found in the oral cavity, co-evolved with us and have become an integral part of who the authors are.
Abstract: This review discusses polymicrobial interactions with the host in both health and disease. As our ability to identify specific bacterial clonal types, with respect to their abundance and location in the oral biofilm, improves, we will learn more concerning their contribution to both oral health and disease. Recent studies examining host- bacteria interactions have revealed that commensal bacteria not only protect the host simply by niche occupation, but that bacterial interactions with host tissue can promote the development of proper tissue structure and function. These data indicate that our host-associated polymicrobial communities, such as those found in the oral cavity, co-evolved with us and have become an integral part of who we are. Understanding the microbial community factors that underpin the associations with host tissue that contribute to periodontal health may also reveal how dysbiotic periodontopathic oral communities disrupt normal periodontal tissue functions in disease. A disruption of the oral microbial community creates dysbiosis, either by overgrowth of specific or nonspecific microorganisms or by changes in the local host response where the community can now support a disease state. Dysbiosis provides the link between systemic changes (e.g. diabetes) and exogenous risk factors (e.g. smoking), and the dysbiotic community, and can drive the destruction of periodontal tissue. Many other risk factors associated with periodontal disease, such as stress, aging and genetics, are also likely to affect the microbial community, and more research is needed, utilizing sophisticated bacterial taxonomic techniques, to elucidate these effects on the microbiome and to develop strategies to target the dysbiotic mechanisms and improve periodontal health.

Journal ArticleDOI
TL;DR: The notion that a co-infection of herpesviruses and specific bacteria causes periodontitis provides a plausible etiopathogenic explanation for the disease and can diminish significantly the periodontal load of herpesvirus.
Abstract: Periodontitis is an infectious/inflammatory disease characterized by the loss of periodontal ligament and alveolar bone. Herpesviruses are frequent inhabitants of periodontitis lesions, and the periodontopathogenicity of these viruses is the topic of this review. In 26 recent studies from 15 countries, subgingival cytomegalovirus, Epstein-Barr virus and herpes simplex virus type 1, respectively, yielded median prevalences of 49%, 45% and 63% in aggressive periodontitis, 40%, 32% and 45% in chronic periodontitis, and 3%, 7% and 12% in healthy periodontium. An active herpesvirus infection of the periodontium exhibits site specificity, is a potent stimulant of cellular immunity, may cause upgrowth of periodontopathic bacteria and tends to be related to disease-active periodontitis. Pro-inflammatory cytokines induced by the herpesvirus infection may activate matrix metalloproteinases and osteoclasts, leading to breakdown of the tooth-supportive tissues. The notion that a co-infection of herpesviruses and specific bacteria causes periodontitis provides a plausible etiopathogenic explanation for the disease. Moreover, herpesvirus virions from periodontal sites may dislodge into saliva or enter the systemic circulation and cause diseases beyond the periodontium. Periodontal treatment can diminish significantly the periodontal load of herpesviruses, which may lower the incidence and magnitude of herpesvirus dissemination within and between individuals, and subsequently the risk of acquiring a variety of medical diseases. Novel and more effective approaches to the prevention and treatment of periodontitis and related diseases may depend on a better understanding of the herpesvirus-bacteria-immune response axis.

Journal ArticleDOI
TL;DR: It can be concluded that improved understanding of the mechanisms associated with osseointegration will provide leads and targets for strategies aimed at enhancing the clinical performance of titanium dental implants.
Abstract: The objective of the present review was to summarize the evidence available on the temporal sequence of hard and soft tissue healing around titanium dental implants in animal models and in humans. A search was undertaken to find animal and human studies reporting on the temporal dynamics of hard and soft tissue integration of titanium dental implants. Moreover, the influence of implant surface roughness and chemistry on the molecular mechanisms associated with osseointegration was also investigated. The findings indicated that the integration of titanium dental implants into hard and soft tissue represents the result of a complex cascade of biological events initiated by the surgical intervention. Implant placement into alveolar bone induces a cascade of healing events starting with clot formation and continuing with the maturation of bone in contact with the implant surface. From a genetic point of view, osseointegration is associated with a decrease in inflammation and an increase in osteogenesis-, angiogenesis- and neurogenesis-associated gene expression during the early stages of wound healing. The attachment and maturation of the soft tissue complex (i.e. epithelium and connective tissue) to implants becomes established 6-8 weeks following surgery. Based on the findings of the present review it can be concluded that improved understanding of the mechanisms associated with osseointegration will provide leads and targets for strategies aimed at enhancing the clinical performance of titanium dental implants.

Journal ArticleDOI
TL;DR: This review focuses on the animal models available for the study of regeneration in periodontal research and implantology; the advantages and disadvantages of each animal model; the interpretation of data acquired; and future perspectives of animal research, with a discussion of possible nonanimal alternatives.
Abstract: Translation of experimental data to the clinical setting requires the safety and efficacy of such data to be confirmed in animal systems before application in humans. In dental research, the animal species used is dependent largely on the research question or on the disease model. Periodontal disease and, by analogy, peri-implant disease, are complex infections that result in a tissue-degrading inflammatory response. It is impossible to explore the complex pathogenesis of periodontitis or peri-implantitis using only reductionist in-vitro methods. Both the disease process and healing of the periodontal and peri-implant tissues can be studied in animals. Regeneration (after periodontal surgery), in response to various biologic materials with potential for tissue engineering, is a continuous process involving various types of tissue, including epithelia, connective tissues and alveolar bone. The same principles apply to peri-implant healing. Given the complexity of the biology, animal models are necessary and serve as the standard for successful translation of regenerative materials and dental implants to the clinical setting. Smaller species of animal are more convenient for disease-associated research, whereas larger animals are more appropriate for studies that target tissue healing as the anatomy of larger animals more closely resembles human dento-alveolar architecture. This review focuses on the animal models available for the study of regeneration in periodontal research and implantology; the advantages and disadvantages of each animal model; the interpretation of data acquired; and future perspectives of animal research, with a discussion of possible nonanimal alternatives. Power calculations in such studies are crucial in order to use a sample size that is large enough to generate statistically useful data, whilst, at the same time, small enough to prevent the unnecessary use of animals.

Journal ArticleDOI
TL;DR: Bioclinical principles are explored that unleash the innate potential of the periodontium to achieve clinically meaningful periodontal regeneration (i.e. space-provision, wound stability and conditions for primary intention healing).
Abstract: Clinical studies have evaluated the effect of conventional periodontal surgical therapy. In general, although some clinical gain in tissue support may be attained, these therapies do not support regeneration of the periodontal attachment. Even though the biological possibility of periodontal regeneration has been demonstrated, the clinical application of this intrinsic potential appears difficult to harness; thus also conceptually most intriguing candidate protocols face clinical challenges. In this review, we explore the bioclinical principles, condiciones sine quibus non, that unleash the innate potential of the periodontium to achieve clinically meaningful periodontal regeneration (i.e. space-provision, wound stability and conditions for primary intention healing). Moreover, limiting factors and detrimental practices that may compromise clinical and biological outcomes are reviewed, as is tissue management in clinical settings.

Journal ArticleDOI
TL;DR: To advance epidemiological knowledge, population-based cross-sectional and longitudinal studies, using appropriate methodologies, should be the future focus of the research agenda of researchers and public health planners in Latin American countries.
Abstract: A decade has passed since we first reviewed the epidemiology of periodontal diseases in Latin America. At that time, lack of population-based studies was the norm and our conclusions were based on very limited evidence. The aim of the present comprehensive review was to update and expand our previous work by providing a broad overview of Latin America and its current social, economic and demographic status and by focusing on the epidemiology of periodontal diseases in Latin American adults published in the last 15 years. The amount of periodontal epidemiological data available has increased but is still restricted to a few countries only. The scope of the literature available has also broadened to include oral health-related quality of life and systemic interactions; however, most studies had methodological limitations that might have biased their results. In general, periodontitis was very prevalent, but severe periodontal destruction was localized. Besides being associated with well-established risk factors, periodontitis was associated with demographics and socio-economic factors in Latin American populations. To advance epidemiological knowledge, population-based cross-sectional and longitudinal studies, using appropriate methodologies, should be the future focus of the research agenda of researchers and public health planners in Latin American countries.

Journal ArticleDOI
TL;DR: It seems that peri-implant mucositis is reversible when appropriately treated, and a combined therapy (mechanical therapy with local antimicrobials as adjuncts) can serve as an alternative to surgical intervention when treating peri -implantits in cases not suitable for surgery.
Abstract: Therapies proposed for the treatment of peri-implant diseases are primarily based on the evidence available from treating periodontitis. The primary objective is elimination of the biofilm from the implant surface, and nonsurgical therapy is a commonly used treatment. A number of adjunctive therapies have been introduced to overcome accessibility problems or difficulties with decontamination of implant surfaces as a result of specific surface characteristics. It is now accepted that following successful decontamination, clinicians can attempt to regenerate the bone that was lost as a result of infection. The ultimate goal is re-osseointegration, and a number of regenerative techniques have been introduced. By reviewing the existing evidence, it seems that peri-implant mucositis is reversible when appropriately treated. Additionally, a combined therapy (mechanical therapy with local antimicrobials as adjuncts) can serve as an alternative to surgical intervention when treating peri-implantits in cases not suitable for surgery. Surgical therapy is an effective method for treating peri-implantitis, and various degrees of success of the use of regenerative procedures have been reported, regardless of whether or not radiographic evidence of defect fill has been achieved. Finally, no matter which therapy is employed, a prerequisite for the long-term stability of treatment results obtained is the ability of the patient to maintain good oral hygiene.

Journal ArticleDOI
TL;DR: A more precise assessment of the distribution and severity of periodontal disease in children and adolescents of Latin America may help policy makers and dentists to institute more effective public health measures to prevent and treat the disease at an early age to avoid major damage to the permanent dentition.
Abstract: Periodontal diseases are a group of infectious diseases that mainly include gingivitis and periodontitis. Gingivitis is the most prevalent form of periodontal disease in subjects of all ages, including children and adolescents. Less frequent types of periodontal disease include aggressive periodontitis, acute necrotizing ulcerative gingivitis and various diseases of herpesviral and fungal origin. This review aimed to retrieve relevant information from Latin America on the prevalence of periodontal diseases among children and adolescents of the region. Gingivitis was detected in 35% of young Latin American subjects and showed the highest frequencies in Colombia (77%) and Bolivia (73%) and the lowest frequency in Mexico (23%). The frequency of gingivitis in subjects from other Latin American countries was between 31% and 56%. Periodontitis may affect <10% of the young population in Latin America, but the data are based on only a few studies. A more precise assessment of the distribution and severity of periodontal disease in children and adolescents of Latin America may help policy makers and dentists to institute more effective public health measures to prevent and treat the disease at an early age to avoid major damage to the permanent dentition.

Journal ArticleDOI
TL;DR: An overview of the current concepts and findings on lasers in periodontal therapy is presented with emphasis on data collected from Latin-American researchers.
Abstract: About 50 years ago, lasers started to be used in periodontal treatment following evidence that wounds produced in animals healed more quickly after being irradiated with low-intensity lasers. Increased production of growth factors, stimulated mainly by red and infrared lasers, may participate in this process by influencing the behavior of various types of cells. High-intensity lasers have been used as an alternative to nonsurgical periodontal therapy in root biomodification and to reduce dentin hypersensivity; low-intensity lasers are frequently employed to improve tissue repair in regenerative procedures and in antimicrobial photodynamic therapy. Despite the abundance of promising data on the advantages of their use, there is still controversy regarding the real benefits of lasers and antimicrobial photodynamic therapy in periodontal and peri-implant treatment. A huge variation in the parameters of laser application among studies makes comparisons very difficult. An overview of the current concepts and findings on lasers in periodontal therapy is presented with emphasis on data collected from Latin-American researchers.

Journal ArticleDOI
TL;DR: This review presents a number of 'proof-of-principle' preclinical models in health and in chronic systemic conditions in which the guided bone regeneration principle was evaluated.
Abstract: The increased use of dental implants and related bone-augmentation procedures creates a need for reliable proof-of-principle preclinical models for evaluating different bone-regenerative techniques. The simulation of clinical scenarios by such models is of importance when the experiments are designed in order for the outcomes to provide basic points of clinical relevance. At the same time, the increased proportion of the population with different chronic diseases of ageing necessitates the need to reproduce these conditions in the same proof-of-principle preclinical models to allow evaluation of the effect of the relevant chronic disease on the bone-healing process. This review presents a number of 'proof-of-principle' preclinical models in health and in chronic systemic conditions in which the guided bone regeneration principle was evaluated.

Journal ArticleDOI
TL;DR: A review of available data on the differential expression of miRNAs in gingival tissues in states of periodontal health and disease addresses specific roles for miRNAAs in molecular and cellular pathways causally linked to periodontitis.
Abstract: MicroRNAs (miRNAs) are a family of small, noncoding RNA molecules that negatively regulate protein expression either by inhibiting initiation of the translation of mRNA or by inducing the degradation of mRNA molecules. Accumulating evidence suggests that miRNA-mediated repression of protein expression is of paramount importance in a broad range of physiologic and pathologic conditions. In particular, miRNA-induced dysregulation of molecular processes involved in inflammatory pathways has been shown to contribute to the development of chronic inflammatory diseases. In this review, first of all we provide an overview of miRNA biogenesis, the main mechanisms of action and the miRNA profiling tools currently available. Then, we summarize the available evidence supporting a specific role for miRNAs in the pathobiology of periodontitis. Based on a review of available data on the differential expression of miRNAs in gingival tissues in states of periodontal health and disease, we address specific roles for miRNAs in molecular and cellular pathways causally linked to periodontitis. Our review points to several lines of evidence suggesting the involvement of miRNAs in periodontal tissue homeostasis and pathology. Although the intricate regulatory networks affected by miRNA function are still incompletely mapped, further utilization of systems biology tools is expected to enhance our understanding of the pathobiology of periodontitis.

Journal ArticleDOI
TL;DR: Evidence is discussed for mechanisms that probably play a role in the altered local inflammatory reactions in the periodontium of patients with diabetes, focusing on local changes in cytokine levels, matrix metalloproteinases, reactive oxygen species, advanced glycation end-products, immune-cell functions, the RANKL/osteoprotegerin axis and toll-like receptors.
Abstract: The impact of diabetes mellitus on the prevalence, severity and progression of periodontal disease has been known for many years and intense efforts have been made to elucidate the underlying mechanisms. It is widely reported that hyperglycemia causes numerous systemic changes, including altered innate immune-cell function and metabolic changes. The aim of this review was to summarize and discuss the evidence for mechanisms that probably play a role in the altered local inflammatory reactions in the periodontium of patients with diabetes, focusing on local changes in cytokine levels, matrix metalloproteinases, reactive oxygen species, advanced glycation end-products, immune-cell functions, the RANKL/osteoprotegerin axis and toll-like receptors. Apart from the systemic effects of diabetes, recent evidence suggests that local changes in the periodontal tissues are characterized by enhanced interactions between leukocytes and endothelial cells and by altered leukocyte functions [resulting in increased levels of reactive oxygen species and of proinflammatory cytokines (interleukin-1β, interleukin-6 and tumor necrosis factor-α)]. These local changes are amplified by the enhanced accumulation of advanced glycation end-products and their interaction with receptors for advanced glycation end-products. Furthermore, the increased levels of proinflammatory cytokines lead to an up-regulation of RANKL in periodontal tissues, stimulating further periodontal tissue breakdown.

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TL;DR: The aim of this review was to describe the main sources of mesenchymal stem cells from tissues in the oral cavity and the potential of these cells in regenerative therapy, with special attention paid to gingival tissue-derived mesenchyl stem cells because they represent the most accessible source of stem cells in the human mouth.
Abstract: Periodontal disease is one of the most common conditions affecting humans, and current treatment strategies, which focus on the removal and long-term control of dental plaque, are generally successful in eliminating active disease and promoting tissue repair. However, regeneration of the supporting structures of the tooth remains an elusive goal and a challenge. The formation of new bone and cementum with supportive periodontal ligament is the ultimate objective, but current regeneration therapies are incapable of achieving this in a predictable way. The regeneration of periodontal tissue requires a combination of fundamental events, such as appropriate level and sequencing of regulatory signals, the presence of progenitor cells, an extracellular matrix or carrier and an adequate blood supply. Based on tissue-engineering concepts, the regeneration process may be modulated by manipulating the signaling pathways of regulatory molecules, the extracellular matrix or scaffold, or the cellular components. The identification of mesenchymal stem cells from bone marrow started a new era in regenerative medicine. Tissue engineering using mesenchymal stem cells became a therapeutic option with several advantages, including high-quality regeneration of damaged tissues without the formation of fibrous tissue, minimal donor-site morbidity compared with autografts and a low risk of autoimmune rejection and disease transmission. The aim of this review was to describe the main sources of mesenchymal stem cells from tissues in the oral cavity and the potential of these cells in regenerative therapy. Special attention is paid to gingival tissue-derived mesenchymal stem cells because they represent the most accessible source of stem cells in the human mouth.

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TL;DR: The present article describes the significance of suturing and appropriate suture materials in current periodontal and implant surgery and Synthetic, nonresorbable, monofilament threads appear to be advantageous.
Abstract: The present article describes the significance of suturing and appropriate suture materials in current periodontal and implant surgery. Synthetic, nonresorbable, monofilament threads appear to be advantageous. The physical and biological properties of such threads remain unchanged with use and, when used in small diameters (i.e. with lower breaking resistance), seem to promote passive wound closure. Wound healing at hard, nonshedding surfaces is conceptually a more complex process than is wound healing in most other sites of the oral cavity. Firm adaptation and stabilization of the flaps by optimal suturing ensures adhesion of the delicate fibrin clot to the nonshedding surface. The early formation and mechanical stability of the blood clot between the mucosal or mucoperiosteal flap and the wound bed are of paramount importance and hence suturing techniques must be considered as a key prerequisite to ensure optimal surgical outcomes. With the sophisticated surgical procedures now applied, there is a greater need for knowledge with regard to the various types of suturing techniques and materials available in order to achieve the above-mentioned goals.

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TL;DR: The current state of research indicates that oral fibroblasts possess unique characteristics and tightly controlled specific functions in wound healing and repair, essential for developing new strategies to control the intraoral wound-healing processes of the individual patient.
Abstract: Fibroblasts are cells of mesenchymal origin. They are responsible for the production of most extracellular matrix in connective tissues and are essential for wound healing and repair. In recent years, it has become clear that fibroblasts from different tissues have various distinct traits. Moreover, wounds in the oral cavity heal under very special environmental conditions compared with skin wounds. Here, we reviewed the current literature on the various interconnected functions of gingival and mucoperiosteal fibroblasts during the repair of oral wounds. The MEDLINE database was searched with the following terms: (gingival OR mucoperiosteal) AND fibroblast AND (wound healing OR repair). The data gathered were used to compare oral fibroblasts with fibroblasts from other tissues in terms of their regulation and function during wound healing. Specifically, we sought answers to the following questions: (i) what is the role of oral fibroblasts in the inflammatory response in acute wounds; (ii) how do growth factors control the function of oral fibroblasts during wound healing; (iii) how do oral fibroblasts produce, remodel and interact with extracellular matrix in healing wounds; (iv) how do oral fibroblasts respond to mechanical stress; and (v) how does aging affect the fetal-like responses and functions of oral fibroblasts? The current state of research indicates that oral fibroblasts possess unique characteristics and tightly controlled specific functions in wound healing and repair. This information is essential for developing new strategies to control the intraoral wound-healing processes of the individual patient.

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TL;DR: New regenerative treatments are clearly needed to improve the predictability of a complete resolution of furcation defects and no meta-analyses are available on the effects of enamel matrix proteins for furcation regeneration.
Abstract: Furcation involvements present one of the greatest challenges in periodontal therapy because furcation-involved molar teeth respond less favorably to conventional periodontal therapy compared with noninvolved molar or nonmolar teeth. Various regenerative procedures have been proposed and applied with the aim of eliminating the furcation defect or reducing the furcation depth. An abundance of studies and several systematic reviews have established the effectiveness of membrane therapy (guided tissue regeneration) for buccal Class II furcation involvement of mandibular and maxillary molars compared with open flap surgery. Bone grafts/substitutes may enhance the results of guided tissue regeneration. However, complete furcation closure is not a predictable outcome. Limited data and no meta-analyses are available on the effects of enamel matrix proteins for furcation regeneration. Enamel matrix protein therapy has demonstrated clinical improvements in the treatment of buccal Class II furcation defects in mandibular molars; however, complete closure of the furcation lesion is achieved only in a minority of cases. Neither guided tissue regeneration nor enamel matrix protein therapy have demonstrated predictable results for approximal Class II and for Class III furcations. Promising preclinical data from furcation regeneration studies in experimental animals is available for growth factor- and differentiation factor-based technologies, but very limited data are available from human clinical studies. Although cell-based therapies have received considerable attention in regenerative medicine, their experimental evaluation in the treatment of periodontal furcation lesions is at a very early stage of development. In summary, the indications and the limitations for currently available treatment modalities for furcation defects are well established. New regenerative treatments are clearly needed to improve the predictability of a complete resolution of furcation defects.

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TL;DR: This volume of Periodontology 2000 discusses the multiple facets of a transition from therapeutic empiricism during the late 1960s, toward regenerative therapies, which is founded on a clearer understanding of the biophysiology of normal structure and function.
Abstract: The ultimate goals of periodontal therapy remain the complete regeneration of those periodontal tissues lost to the destructive inflammatory-immune response, or to trauma, with tissues that possess the same structure and function, and the re-establishment of a sustainable health-promoting biofilm from one characterized by dysbiosis. This volume of Periodontology 2000 discusses the multiple facets of a transition from therapeutic empiricism during the late 1960s, toward regenerative therapies, which is founded on a clearer understanding of the biophysiology of normal structure and function. This introductory article provides an overview on the requirements of appropriate in vitro laboratory models (e.g. cell culture), of preclinical (i.e. animal) models and of human studies for periodontal wound and bone repair. Laboratory studies may provide valuable fundamental insights into basic mechanisms involved in wound repair and regeneration but also suffer from a unidimensional and simplistic approach that does not account for the complexities of the in vivo situation, in which multiple cell types and interactions all contribute to definitive outcomes. Therefore, such laboratory studies require validatory research, employing preclinical models specifically designed to demonstrate proof-of-concept efficacy, preliminary safety and adaptation to human disease scenarios. Small animal models provide the most economic and logistically feasible preliminary approaches but the outcomes do not necessarily translate to larger animal or human models. The advantages and limitations of all periodontal-regeneration models need to be carefully considered when planning investigations to ensure that the optimal design is adopted to answer the specific research question posed. Future challenges lie in the areas of stem cell research, scaffold designs, cell delivery and choice of growth factors, along with research to ensure appropriate gingival coverage in order to prevent gingival recession during the healing phase.

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TL;DR: The purpose of this article was to provide an overview of the cell interactions and cytokine networks specifically involved in the pathogenesis of periodontitis, and models and paradigms from recent research in this area are presented.
Abstract: A large amount of information is available, in the medical literature, on the molecular and immunological mechanisms in which T- and B-cells are involved in the pathogenesis of inflammatory diseases. This review attempts to describe the most important features of the T-cell subsets and their cytokine networks in periodontitis, including the interaction of pathogens with different cell subsets and their gene-expression profiles. Additionally, the known interactions of T- and B-cell subsets in periodontitis are described. The purpose of this article was to provide an overview of the cell interactions and cytokine networks specifically involved in the pathogenesis of periodontitis, and models and paradigms from recent research in this area are presented. However, the review of the literature also revealed that relatively little is known about the genetic or structural factors that confer cross-reactivity of natural and/or autoreactive antibodies in the immunopathogenesis of periodontitis. Pathogens, in turn, are continuously evolving and creating mechanisms to evade immunological reactions controlled and modulated by T- and B-cells.