Advances in Dental Research最新文献

Recent rapid advances in "-omics" technologies have yielded new insights into the interaction of the oral microbiome with its host. Associations of species that are usually considered to be acid-tolerant with caries have been confirmed, while some recognized as health-associated are often present in greater proportions in the absence of caries. In addition, some newly identified bacteria have been suggested as potential contributors to the caries process. In spite of this progress, two major challenges remain. The first is that there is a great deal of heterogeneity in the phenotypic capabilities of individual species of oral bacteria. The second is that the most abundant taxa in oral biofilms display remarkable phenotypic plasticity, i.e., the bacteria associated most strongly with health or with caries can morph rapidly in response to alterations in environmental pH, carbohydrate availability and source, and oxygen tension and redox environment. However, new technologic advances coupled with "old-fashioned microbiology" are starting to erode the barriers to a more complete understanding of oral biofilm physiology and ecology, and in doing so are beginning to provide insights for the creation of novel cost-effective caries control therapies.

Hundreds of bacterial species inhabit the oral cavity. Many of these have never been cultivated and can be assessed only with DNA-based techniques. This new understanding has changed the paradigm of the etiology of oral disease from that associated with 'traditional pathogens' as being primarily responsible for all diseases. Increasingly, associations between oral bacteria and systemic diseases are being reported. The emergence of antibiotic resistance is alarming and calls for in-depth studies of biofilms, bacterial physiology, and a body-wide approach to infectious diseases. We propose that the borderline between commensal bacteria and pathogens is no longer discrete. In a field of science where so many of the established paradigms are being undermined, a thorough analysis of threats and opportunities is required. This article addresses some of the questions that can be raised and serves to identify research opportunities and needs to leverage the prevention of oral diseases through novel antimicrobial strategies.

The population of the world is aging. A greater proportion of older people are retaining increasing numbers of natural teeth. Aging is associated with changes in oral architecture and muscle weakness, making personal oral hygiene more difficult, particularly for the oldest and most frail individuals. Furthermore, there is exposure of root dentin with its higher pH for demineralization in addition to enamel as a substrate for caries. Aging is also associated, for many in the developed world, with taking multiple medications, with the associated risk of dry mouth. These variables combine to increase caries risk in older vulnerable populations. Caries occurs on both the crowns of teeth (predominantly around existing restorations) and the exposed roots. Prevention needs to be aggressive to control disease in this combination of circumstances, with multiple strategies for limiting the damage associated with caries in this population. This paper explores the evidence that is available supporting preventive strategies, including fluorides in various forms, chlorhexidine, and calcium phosphate supplementation.

Dental erosion is the non-carious dental substance loss induced by direct impact of exogenous or endogenous acids. It results in a loss of dental hard tissue, which can be serious in some groups, such as those with eating disorders, in patients with gastroesophageal reflux disease, and also in persons consuming high amounts of acidic drinks and foodstuffs. For these persons, erosion can impair their well-being, due to changes in appearance and/or loss of function of the teeth, e.g., the occurrence of hypersensitivity of teeth if the dentin is exposed. If erosion reaches an advanced stage, time- and money-consuming therapies may be necessary. The therapy, in turn, poses a challenge for the dentist, particularly if the defects are diagnosed at an advanced stage. While initial and moderate defects can mostly be treated non- or minimally invasively, severe defects often require complex therapeutic strategies, which often entail extensive loss of dental hard tissue due to preparatory measures. A major goal should therefore be to diagnose dental erosion at an early stage, to avoid functional and esthetic impairments as well as pain sensations and to ensure longevity of the dentition.

Streptococcus mutans has been implicated as the major acid-producing (cariogenic) bacterium. Dietary sugars and other factors may cause an imbalance of oral microflora that enables S. mutans to become dominant in the multi-species biofilms on the tooth surface, which could lead to dental caries. The application of broad-spectrum antimicrobials often results in re-colonization and re-dominance of S. mutans within oral flora, while in contrast, therapies capable of selective elimination of S. mutans from oral microbial communities may help to re-establish the normal flora and provide long-term protection. C16G2, a novel synthetic antimicrobial peptide with specificity for S. mutans, was found to have robust killing efficacy and selectivity for S. mutans in vitro. A subsequent pilot human study found that a single application of C16G2 in the oral cavity (formulated in a mouthrinse vehicle) was associated with a reduction in plaque and salivary S. mutans, lactic acid production, and enamel demineralization during the entire 4-day testing period. C16G2 is now being developed as a new anticaries drug.

In the past decades, numerous studies have looked at the anticaries effects of polyols, particularly xylitol, and a great many studies have focused on xylitol's antimicrobial properties. Researched vehicles have mostly included chewing gums, followed by lozenges/candies, toothpastes, and others (e.g., syrup). Good evidence supports the claims that xylitol is non-cariogenic and has a dose-/frequency-dependent antimicrobial effect on dental plaque/mutans streptococci, and that polyol use is very safe. However, interpretation of caries data has been controversial, due in part to variability in study designs, formulations/dosages tested, and outcomes reported (e.g., many caries studies have a "no gum" control, limiting the interpretation of the polyol's benefit; few studies have compared different polyols side-by-side, or in adults). Even when the level/strength of high-quality anticaries evidence is still limited, most recent systematic reviews have consistently concluded that the habitual use of sucrose-free xylitol or polyol-combination chewing gum/ lozenges is an effective adjunct in coronal caries prevention. Consequently, many health organizations worldwide are supporting this recommendation for at-risk populations. However, most experts agree that well-designed, placebo-controlled randomized clinical trials (RCTs) (focusing on efficacy, feasibility, adherence, dosage, vehicle, synergism with other preventive strategies, and cost) are still needed in target populations worldwide to reach definitive caries-preventive/therapeutic recommendations.

Antimicrobial methods to augment fluoride-mediated caries inhibition are necessary. Several methods are described here, but none was considered likely to be as effective as fluoride usage. None had been tested in effective models to demonstrate their ability to act either additively or synergistically with fluoride-containing toothpastes. Dental caries is a biofilm-mediated disease: The composition of the biofilm associated with caries initiation and progression is diverse. Caries-associated taxa - including mutans streptococci, lactobacilli, bifidobacteria, and yeasts - may be useful surrogate markers for in vivo investigations. In vitro testing should progress from single-species planktonic cells to multi-species biofilms prior to essential testing in randomized control trials (RCTs). Modern high-throughput sequencing techniques need to be applied to the study of bacterial acquisition from birth and of the composition of the biofilm associated with the formation of white-spot lesions. The determination of the functions of the biofilm and the phenotype of the bacterial components may be determined by RNA-seq techniques, since they must be conserved between caries lesions and will include the ability to produce acids and survive and proliferate in acidic conditions. The application of such methods will significantly improve our understanding of the etiology and progression of dental caries.

The first ICNARA conference (International Conference on Novel Anticaries and Remineralizing Agents) was held in Chile in January, 2008, and the proceedings were published in Advances in Dental Research (Volume 21, 2009). That issue of Advances summarized the state of the science and set a research agenda for the future for two key components of caries management, namely, antibacterial agents and remineralizing agents. The second conference (ICNARA 2, January 2012) provided an update on science and new directions for research and clinical practice. Over the past decade, renewed efforts have been made across the world to establish proven methods of caries risk assessment and to provide direction for improved methods of caries management based upon risk levels. Evidence-based caries risk assessment tools are now available. The need for improved therapy to reduce the bacterial challenge that initiates the caries process, and to enhance remineralization, is now very clear. Fluoride therapy alone is insufficient to control the caries process in high-risk individuals. New remineralizing and anticaries products and new delivery systems are in development, and ICNARA 2 presents future technology for the management of dental caries.

With more than 50 years of clinical success, fluoride serves as the gold standard agent for preventing tooth decay. In particular, the action of fluoride facilitates saliva-driven remineralization of demineralized enamel and alters solubility beneficially. Still, tooth decay remains problematic, and one way to address it may be through the development of new mineralizing agents. Laboratory and clinical studies have demonstrated that the combination of fluoride and functionalized β-tricalcium phosphate (fTCP) produces stronger, more acid-resistant mineral relative to fluoride, native β-TCP, or fTCP alone. In contrast to other calcium-based approaches that seem to rely on high levels of calcium and phosphate to drive remineralization, fTCP is a low-dose system designed to fit within existing topical fluoride preparations. The functionalization of β-TCP with organic and/or inorganic molecules provides a barrier that prevents premature fluoride-calcium interactions and aids in mineralization when applied via common preparations and procedures. While additional clinical studies are warranted, supplementing with fTCP to enhance fluoride-based nucleation activity, with subsequent remineralization driven by dietary and salivary calcium and phosphate, appears to be a promising approach.