Periodontal regeneration of intrabony defects: an evidence-based treatment approach

A task force of periodontists established clinical and histologic outcomes (goals) for the treatment of intrabony defects and researched the literature for techniques that would most predictably achieve these goals. The group also identified factors that could influence predictability. The treatment outcomes selected by the task force included regeneration of a true attachment apparatus; gain in bone and probing attachment levels; reduction in probing pocket depth; minimal gingival recession; increased patient comfort; esthetic appearance and state of wellness; and maintenance of health, comfort, and function over time. Based on evidence, it was concluded that guided tissue regeneration, guided tissue regeneration combined with the use of decalcified freeze dried bone allografts and freeze-dried bone allografts alone are the most predictable regenerative procedures for achieving selected treatment outcomes. Various factors, such as patient characteristics, the morphology of the defect, and the surgical technique can influence the healing response of intrabony defects. Patient factors, such as plaque control, compliance, and cigarette smoking, can directly affect predictability of periodontal regeneration. Defect selection is critical, and deep and narrow defects are the most predictable response to regenerative procedures. The number of remaining bony walls is important in grafting procedures, but their influence is questionable in guided tissue regeneration. Various technical procedures, such as flap design, defect debridement, and wound protection, may influence the predictability of regeneration.     

Biological influence of some crown and bridge restorative materials finished and polished by different techniques

Fixed restorations should satisfy certain biologic requirements and they must not be injurious to the surrounding living tissues as pulp, periodontal ligament, alveolar bone and gingiva. It is best to terminate preparations above the gingival margin but for retention and esthetics considerations the margins of the fixed restorations could be placed subgingivally. In recent years, the biologic effects of dental restorative materials on the gingiva and periodontal tissues have been better appreciated. A rough surface restoration attracts and retains bacterial plaque and irritates the surrounding soft tissues which is injurious to the living supporting structure of the abutments.     

The design and implementation of trials of host modulation agents

Over the last two decades it has become more evident that although oral microorganisms are essential agents of periodontal pathogenesis, interpatient variability in the host response is a major determinant of the expression of periodontal disease extent and severity. Data from animal models and human studies have identified many of the components of the host inflammatory response which serve as critical mediators of clinical inflammation, attachment loss, and bone resorption. Studies suggest that certain pharmacologic agents, which act at a molecular level to block specific inflammatory mediators, appear to attenuate disease progression. These promising findings herald a new era in periodontal medicine. Anti-infective therapies may soon be supplemented with anti-inflammatory pharmacological agents. However, there are many unanswered issues regarding formulation design, clinical application, potential indication claims, and clinical study design. Furthermore, current considerations of fundamental mechanisms of pathogenesis, as well as new data from epidemiologic studies emphasizing the multifactorial nature of disease, are changing the underlying assumptions which have served to guide our design of anti-infective drug trials over the last two decades. There are new questions regarding appropriate outcome measurements which are to be reconsidered. For example, the measurement of a change in periodontal disease status, either during progression or in response to therapy, is fundamentally unidimensional and may be only mildly informative when one considers that the disease is multifactorial by nature. Using an example from intensive care medicine, pathophysiologic studies of septic shock have demonstrated that the microbial dose and the host inflammatory mediator response are far better predictors of patient morbidity and mortality than any combination of clinical signs associated with clinical shock. Clinical trials of anti-cytokine and anti-inflammatory drugs to treat shock are now designed and conducted taking strategic advantage of this knowledge by including measurements of microbial dose and host response. It appears prudent that the design and implementation of clinical trials of host modulation agents also benefit from our current insights into pathogenesis and not represent a template-driven adaptation of historical, anti-infective clinical trial protocols.     

The evolution of clinical periodontal therapy

Periodontal diseases are considered as old as the history of mankind, Magical, religious and herbal treatments were demonstrated in almost all of the early writings. However, methodical, carefully reasoned therapeutic approaches did not exist until the middle-ages and modern treatment with a scientific base and sophisticated instrumentation did not develop until the 18th century. Prior to the 1950s, diseases were mostly treated by root debridement and the extraction of the affected teeth. Until the 1970s, it was primarily the symptoms of periodontal diseases that were treated. The goal was radical elimination of the periodontal pocket (resective therapy). The means were gingivectomy, flap procedures and osseous surgery. The disadvantages were the massive sacrifice of periodontal tissues, lack of regeneration and clinically elongated teeth. These disadvantages, along with the realization of the importance of aetiologic agents, raised questions about the necessity of total pocket elimination, and the control of subgingival infection by a thorough scaling and root planing (nonsurgical therapy), with and without antibiotics, became a commonly used treatment during the 1980s. Comparative longitudinal studies, surgical versus nonsurgical, demonstrated that both surgical and nonsurgical therapy result in limited regeneration and healing with a long junctional epithelium. The most important aspects of today's modern concept of periodontal therapy are causal, regenerative, and specific for disease type and severity. Although the regeneration of the periodontium can be accomplished with the biological principles of guided tissue regeneration and graft materials, compared to conventional methods, the restoration of a completely normal periodontal status has not yet been achieved. We are about to reach our ultimate goals and presently, the more promising research directions for a substantial regeneration seems to lie in biological mediators. Although the future of periodontal therapy is bright, it is still of critical importance to have a preventive strategy to keep individuals healthy beforehand.     

Nonsteroidal anti-inflammatory agents: potential modifiers of periodontal disease progression

The most recent studies of NSAIDs as potential modifiers of periodontal disease progression are reviewed. These studies indicate that NSAIDs have the ability to alter or control the progression of periodontal disease. Reductions in gingival inflammation and in bone loss have been observed following the administration of various NSAIDs. In some cases, bone gain has been achieved. More research is required to determine the possible long-term side effects associated with the chronic usage of NSAIDs, as well as to achieve consensus on the most effective drug for the control of periodontal disease. Until this occurs, and this application of NSAIDs receives government approval, the use of these drugs to control periodontal disease is not recommended.     

The clinical aspects of hydrocephalus in children

The removal of tooth structure during preparation results in varying degrees of pulpal hyperemia. The ability of the pulpal tissue to respond either by recovery or degeneration depends in part upon the adequacy and fit of the provisional restoration. The response of the gingival tissue also depends on a large degree on the success of the temporary coverage. Provisional restorations are commonly given less attention and importance thereby biologic, mechanical, and esthetic considerations are not adequately met. Since a provisional restoration must be made or improvised during the same appointment in which the abutment teeth are prepared, costly chairside time most often leads to an unacceptable restoration. Failures such as color instability, color incompatibility, inappropriate anatomic contours, fractures, occlusal disharmony, changes in tooth position, gingival inflammation, and unhealthy periodontal conditions are usually encountered. A technique of fabricating an exacting provisional restoration with compliance to optimum quality is presented.     

Methods for evaluating biological response modifiers

Biological response modifiers (BRM) are a new approach of cancer treatment. The guidelines for their evaluation are comparable to those used for evaluating conventional anticancer treatments. However, it is more difficult to assess their efficacy and toxicity because of their own properties and of the characteristics of underlying diseases. The objectives of studying BRM efficacy are the following : 1- to confirm the pharmacodynamic effect observed in experimental models; 2- to assess the benefit for the patient. Phase II studies can occasionally be performed in healthy volunteers. Efficacy criteria are objective response rate, progression free survival, overall survival or, for hematopoietic growth factors, more specific criteria. In randomized phase III studies patients in the control arm can be observed without treatment, or receive a placebo or a standard treatment. As regards toxicity, side effects specifically related to the use of BRM are the synthesis of cytokines, the stimulation of immune system, the stimulation of tumor growth, the synthesis of anti-mouse of anti-BRM antibodies.     

Stress and coping behaviors of substance-abusing mothers

BACKGROUND: The guided regeneration of periodontal tissues demonstrated to represent a therapeutical technique with predictable results. It has been observed that different materials, used as regenerative membranes, offer very similar results. Unconventional materials too, like the rubber dam, seem to be useful in the guided tissues regeneration technique. The object of the present study has been to comparatively evaluate the effectiveness of Gore-Tex and rubber dam-made membranes in the therapy of intra-osseous periodontal defects. MATERIALS AND METHODS: Six patients with two similar intra-osseous defects, participated in the study; one defect has been treated using, during the surgical intervention, a Gore-Tex membrane, while the other has received, a fragment of sterile rubber dam membranes. The principal clinical parameters of the periodontal health (probing depth -PD- and attachment loss -AL-) has been evaluated in both the defects before and 6 months after the periodontal surgery. RESULTS AND CONCLUSIONS: The results have showed that there are not statistically significant differences (p > 0.05) in the healing of the intra-osseous defects treated by rubber dam or Gore-Tex. The conclusion is drawn that the rubber dam can represent a valid and cheap alternative to the materials traditionally used in the regenerative surgery of the periodontal tissues.     

Glucose modulates growth of gingival fibroblasts and periodontal ligament cells: correlation with expression of basic fibroblast growth factor

Diabetes mellitus is a systemic disease with profound effects on oral health and periodontal wound healing. Uncontrolled diabetes adversely affects surgical wound healing and is often associated with abnormal proliferation of fibroblasts, excessive angiogenesis and poor bone regeneration. Human gingival fibroblasts and periodontal ligament cells from both diabetics and non-diabetics were evaluated for growth responses following culture in 20 mM glucose, a concentration compatible with blood glucose levels in uncontrolled diabetics. Gingival fibroblasts derived from 9 non-diabetic patients and 3 insulin-dependent diabetics either proliferated or showed little change of growth in elevated glucose. Enhanced proliferation was observed following 1 wk of culture in glucose. Growth of periodontal ligament cells from 5 non-diabetic patients was inhibited by 20 mM glucose. Fibroblasts that were markedly growth stimulated were probed for expression of basic fibroblast growth factor (bFGF) using a reverse-transcribed polymerase chain reaction (RT-PCR). Results indicate that fibroblasts exhibiting the greatest increase in growth in response to high glucose also exhibited increased expression of bFGF. No changes were observed in mRNA expression for platelet-derived growth factor-AA, platelet-derived growth factor-BB, insulin-like growth factor and transforming growth factor-beta 1. Mitogenic effects induced by the cytosol of fibroblasts exhibiting increases of growth in 20 mM glucose were abrogated by neutralizing antibodies to bFGF. In addition, some periodontal ligament cells that were growth inhibited by high glucose had reduced expression of bFGF. These data suggest that bFGF may play a role in the abnormal wound healing associated with periodontal surgery of uncontrolled diabetics.     

In vitro, in vivo, and tissue retrieval studies on particulate debris

The biologic effects of wear debris are an important factor limiting the longevity of total joint replacements. In vivo, in vitro, and tissue retrieval studies have underlined a central role for the macrophage in the etiology of loosening and periprosthetic osteolysis. Wear particles from the materials used for total joint replacement activate macrophages to secrete proinflammatory factors. Complex interactions between macrophages and other cells stimulate bone resorption and suppress bone formation at the prosthetic interface. To improve the long term outcome of joint replacements, future research must find innovative approaches to minimize the production and biologic effects of wear debris.     

The influence of endodontic treatment upon periodontal wound healing

The interrelationship between periodontal and endodontic disease has aroused much speculation, confusion, and controversy. Pulpal and periodontal problems are responsible for more than 50% of tooth mortality today. Diagnosis is often difficult since these diseases have been studied primarily as separate entities. The toxic substances of the pulp may initiate periodontal defects through canal ramifications and patent dentinal tubules, thus impairing wound healing in regenerative procedures. Although no studies exist addressing the direct effect of pulpal infection on the outcome of guided tissue regeneration (GTR) procedures, several studies do indicate that pulpal status may play a significant role toward the end results of GTR. This review article discusses the potential influence of endodontic treatment on the long-term outcomes of GTR. Potential pathways between the pulp and periodontal ligament, which may be responsible for the failure of the regeneration of new periodontal attachment apparatus, are explored. Examination and review of the clinical and research findings in the literature relating to perio-endo lesions are made to demonstrate that a negative influence may exist between GTR outcomes and the status of the pulp.     

Immunotherapy of renal cell carcinoma

Immunologic approaches to the therapy of metastatic renal cell carcinoma have provided moderate improvement in response rates for a disease that is extremely resistant to all forms of treatment. This article reviews recent clinical efforts using immunotherapy for renal cell carcinoma, including the adoptive transfer of cytotoxic killer cells and/or the use of biologic response modifiers, such as interferon and interleukin-2.     

Hepatocyte proliferation and gene expression induced by triiodothyronine in vivo and in vitro

Subcutaneous injections of hormone triiodothyronine in rats resulted in peak blood levels at 24 hr with return to baseline by 96 hr. The injections stimulated a liver regeneration response that resembled in timing and in magnitude of DNA synthesis (peak, 24 hr) that induced by 40% hepatic resection. The principal proliferation was of hepatocytes. Although there were some temporal differences from the gene expression of transforming growth factor-alpha, transforming growth factor-beta, and c-Ha-ras that are known to follow partial hepatectomy, the overall profile of these changes was similar to those after partial resection. The effect was liver specific and could be reproduced three times with no diminution in response in the same animal with injections at 10-day intervals. No response was detected in kidney or intestine. This effect in intact animals contrasted with the minimal ability of triiodothyronine to stimulate hepatocytes in culture. However, when the culture medium was enriched with epidermal growth factor, there was a dose-related response to triiodothyronine. The totality of these experiments provides a preliminary basis for the creation with pharmacological techniques of an in vivo hyperplastic hepatic condition permissive of transfection of new genes, as an alternative to partial hepatectomy. Although triiodothyronine was the test agent used, other hepatic growth factors singly or in combination could be candidates for this purpose.     

Genetic variations in cytokine expression: a risk factor for severity of adult periodontitis

Periodontitis is a collection of chronic inflammatory diseases that are caused by specific bacteria. The bacteria activate inflammatory mechanisms in the periodontal tissues that destroy collagen and bone that support the teeth. Although bacteria are essential for the initiation of periodontitis, the quantity and types of bacteria have not been sufficient to explain the differences in disease severity. In recent years, it has become evident that for many common chronic diseases, there are modifying factors that do not cause the disease but rather amplify some disease mechanisms to make the clinical condition more severe. There are now data to suggest that a few factors which amplify the inflammatory process make people susceptible to an increased severity of periodontitis. Studies of untreated disease in Sri Lanka identified 3 patterns of disease progression. Studies in twins suggested that part of the clinical characteristics of periodontitis may be explained by genetic factors, but previous attempts to identify genetic markers for periodontitis have been unsuccessful Some genetic variations (polymorphisms) are commonly found in our population and represent a mechanism by which individuals may exhibit variations within the range of what is considered biologically normal. Since certain cytokines are key regulators of the inflammatory response and are important in periodontitis, we investigated the relationship between genetic variations associated with cytokine production and periodontitis severity. There are several polymorphisms in the cluster of genes that influence IL-1 biological activity. In recent clinical trials, two of these polymorphisms, when found together, have been associated with a significant increase in the risk for severe generalized periodontitis. Genetic association with periodontitis was evident only when smokers were excluded from the analysis, confirming the importance of smoking, and suggesting that both smoking and the IL- I genotype are independent factors in severe periodontitis. It is notable that 1 polymorphism associated with severe periodontitis in our study is also known to correlate with a 2- to 4-fold increase in IL-1 beta production. These findings are consistent with the current model of how genetic factors influence common chronic diseases. If we apply this model to periodontitis, it would involve the following: 1) a disease-initiating factor that would undoubtedly be specific bacteria such as Porphyromonas gingivalis, Actinobacillus actinomycetemcomitans. and Bacteroides forsythus: and 2) modifiers of disease mechanisms that account for the clinical severity, including smoking, the IL-I genotype, certain systemic diseases, and psychosocial stress. The association of the IL-I genotype with severe periodontitis is consistent with several lines of periodontal research. Several studies have suggested there is a substantial genetic influence in periodontal disease. Although specific genetic markers have been identified in the uncommon juvenile forms of periodontitis, previous studies of specific genetic markers in adults with periodontitis have not been encouraging. Many investigators have, however, demonstrated a role for IL-1 in the initiation and progression of periodontitis. For example, IL-1 activates the degradation of the extracellular matrix and bone of the periodontal tissues, and elevated tissue or gingival fluid levels of IL-1 beta have been repeatedly associated with periodontitis. In addition, IL-1 is a strong enhancer of tissue levels of PGE2 and TNF-alpha. The association of severe periodontitis with smoking and the IL-1 genotype suggest a role for these factors in the pathogenesis of periodontitis. The finding that host modifying factors are associated with severe periodontitis suggest a biological mechanism by which some individuals, if challenged by bacterial accumulations, may have a more vigorous immunoinflammatory response, leading to more severe clinical disease. (ABSTRACT     

Tobacco and smoking: environmental factors that modify the host response (immune system) and have an impact on periodontal health

This review summarizes the current data on the effects of smoking and tobacco on the immune system and its potential impact on periodontal health. Smokers are 2.5-6 times more likely to develop periodontal disease than non-smokers, and there is evidence for a direct correlation between the number of cigarettes smoked and the risk of developing disease. Tobacco users also tend to exhibit increased severity of periodontal disease. Direct correlations between tobacco use and increased attachment loss and pocket depth and reduced bone crest height have been reported. Although the correlation between tobacco use and periodontal disease is quite strong, the role of tobacco in the pathogenesis of periodontal disease is uncertain. Recent studies indicate that one potential mechanism is that tobacco use exacerbates periodontal disease because it alters the immune response to periodontal pathogens. Indeed, smokers exhibit increased numbers of peripheral blood mononuclear phagocytes which appear to be functionally compromised. Inadequate phagocyte activity could reduce the clearance of pathogens from the oral cavity and thereby facilitate the development of periodontal disease. Tobacco-exposed B- and T-lymphocytes exhibit reduced proliferative capacities which could limit the production of protective immunoglobulins against oral pathogens. The risk factors for periodontal disease can be broadly classified as genetic, environmental, host-response factors, and host-related factors such as age. Tobacco, an environmental factor, undermines the host response and may facilitate the development and progression of periodontal disease. This review highlights the inter-relatedness of two of the risk factors associated with periodontal disease.     

Outcome variables for the study of periodontal regeneration

The most reliable outcome variable for assessing periodontal regeneration is human histology; however, the morbidity associated with this technique makes it feasible only in isolated case studies designed to prove that a drug, device, or technique is capable of regenerating the lost periodontium including bone, cementum, and functionally oriented periodontal ligament. In the absence of this genuine variable, other "surrogate" variables must be used. Of these, measurement of new bone is the primary alternative. Direct bone measurements, including linear and volumetric assessment, are by far the best tools; however, the need for a second surgical procedure is a definite drawback of this technique. To overcome this problem, other outcomes have been employed: sounding bone measurements is a less invasive method, albeit it is also less accurate. Another tool that has been tested extensively is radiographic analysis. Conventional radiography is not useful in most regenerative trails where minimal or no crestal changes occur. The use of standardized radiographs and image processing techniques to measure alveolar bone changes has not significantly enhanced the applicability of this method. Digital subtraction radiography (DSR) offers some improvement over previous techniques; however, the correlation between the magnitude of clinical bone changes and changes in the digital image is yet to be substantiated. Other variables have been successfully used in regenerative studies. These include clinical attachment level changes, change in probing depth, and gingival recession. The information derived from these variables, especially attachment level changes, supplement and substantiate the direct bone measurements. Other variables that may be monitored are those associated with plaque formation, periodontal pathogens and gingival inflammation; while not direct measures of regeneration, these variables are likely to affect future prognosis and treatment stability. In summary, direct bone measurements are the most ideal surrogate outcome variable, although clinical attachment level measurements are commonly used in large-scale regenerative clinical trials. Clinical response may be assessed at different time intervals; however, the endpoint measurements for regenerative studies should be taken at least 12-months postoperatively.     

Three-dimensional dynamic behaviour of the human knee joint under impact loading

Over the past 50 years, we have made remarkable advances in the use of bionic devices and solid organ transplants as replacement parts for failing tissues and organs. These approaches to tissue restoration, however, have a number of drawbacks. Thus, a new approach, regenerative biology and engineering, has been developed, consisting of the strategies of cell transplantation, bioartificial tissue constructs, and stimulation of regeneration in vivo. Cell transplants have been successfully used to restore articular cartilage and to treat Parkinson's disease in humans. In rats, transplanted fetal and embryonic stem cell line-derived cardiomyocytes have been shown to differentiate and integrate well with the ventricular myocardium, suggesting the feasibility of using such transplants to restore damaged cardiac muscle. Diabetic symptoms in humans have been alleviated by implanting a bioartificial pancreas consisting of islet cells microencapsulated in alginate. Hydroxyapatite matrixes can stimulate the regeneration of bone across large gaps. Collagenous artificial matrixes can stimulate the regeneration of dermis, and peripheral nerve grafts embedded in a fibrin clot containing fibroblast growth factor-1 stimulate some regeneration of spinal cord axons in adult rats. Future research in regenerative biology will focus on several issues: (1) providing adequate sources of cells for transplantation and bioartificial tissue construction and determining ways to prevent these cells from coming under attack by the immune system, (2) developing new and better materials to build better bionic devices and bioartificial constructs and to stimulate regeneration in vivo, (3) determining how many tissues of the body might contain reserve cells for regeneration in vivo, (4) analyzing the molecular differences between cells and environments of regenerating versus nonregenerating tissues, and (5) understanding the factors and mechanisms involved in the proliferation and patterning of regenerating tissues.