Advances in Dental Research最新文献

This article aims to outline the early development of a King's College London dental spinout company, Reminova, formed to commercialize a novel clinical method of caries remineralization: electrically accelerated and enhanced remineralization (EAER). This method is being developed to address the unmet clinical need identified by modern caries management strategies to keep enamel "whole" through remineralization of clinical caries as a form of nonoperative caries treatment for initial-stage and moderate lesions. A progressive movement within dentistry is shifting away from the restorative-only model, which, it is suggested, has failed. The high prevalence of initial-stage caries across populations provides a significant opportunity to prevent restorations and reduce repeat restorations over a patient's lifetime. Reminova has set out to provide a method to repair lesions without drilling, filling, pain, or injections. The article outlines the rationale for and the chronological stages of the technology and company development. It then outlines corroborative evidence to show that EAER treatment can, in this preliminary in vitro investigation, remineralize clinically significant caries throughout the depth of the lesion as measured by Knoop microhardness and corroborated by scanning electron microscopy. Furthermore, the presented data show that EAER-treated enamel is harder than the healthy enamel measured nearby in each sample and is very similar in appearance to healthy enamel from the subjective interpretation made possible by scanning electron microscopy imagery. The data presented also show that this more "complete" remineralization to a high hardness level has been achieved with 2 remineralizing agents via in vitro human tooth samples. The broad clinical potential of this new treatment methodology seems to be very encouraging from these results. Reminova will strive to continue its mission, to ensure that, in the future, dental teams will not need to drill holes for the treatment of initial-stage and moderate caries lesions.

Carious lesions develop in tooth surfaces where there is an imbalance of the processes of acid and alkali production by supragingival biofilms. Since low pH is the main driving factor in the development of carious lesions, most efforts to identify an effective anticaries therapy have focused on targeting the acid-producing bacteria and their mechanisms of acid production. An expanding area of oral microbiology has now been devoted to explore microbial metabolic activities that help to neutralize biofilm pH and thus inhibit the caries process. Arginine metabolism via the arginine deiminase pathway (ADS) produces alkali in the form of ammonia that counteracts the effects of biofilm acidification from bacterial glycolysis. ADS also functions as an adaptive strategy used by certain bacteria to thrive in oral biofilms. Substantial evidence accumulated from laboratory and clinical observations supports the hypotheses that measurements of arginine metabolism via ADS may serve as an important caries risk assessment criterion and that providing arginine regularly to supragingival biofilms can be an effective therapy for caries intervention. This article reviews the potential of arginine-based therapies such as the use of arginine as prebiotic, ADS⁺ strains as probiotics, and oral care formulations containing arginine for prevention and management of dental caries.

To demonstrate that Caries Management by Risk Assessment (CAMBRA) can be successfully implemented in dental practice, 30 dentists were recruited to perform a 2-y CAMBRA trial. Twenty-one dentists (18 private practices, 3 community clinics) participated in a randomized, controlled, parallel-arm, double-blind clinical trial with individual-level assignment of 460 participants to standard of care (control) versus active CAMBRA treatment (intervention). Control or active antimicrobial and remineralizing agents were dispensed at baseline and 6-, 12-, 18-, and 24-mo recall visits according to risk level and assigned treatment arm. Primary outcome measure was dentist-determined caries risk level at recall. Among initially high-risk participants, secondary outcomes were recorded disease indicators. Generalized estimating equations were used to fit log-linear models for each outcome while accounting for repeated measurements. At 24 mo, follow-up rates were 34.3% for high-risk participants (32.1% intervention, 37.1% control) and 44.2% for low-risk participants (38.7% intervention, 49.5% control). Among 242 participants classified as high caries risk at baseline (137 intervention, 105 control), a lower percentage of participants remained at high risk in the intervention group (statistically significant at all time points). At 24 mo, 25% in the intervention group and 54% in the control group remained at high risk ( P = 0.003). Among 192 participants initially classified as low risk (93 intervention, 99 control), most participants remained at low risk. At 24 mo, 89% in the intervention group and 71% in the control group were low caries risk ( P = 0.18). The percentage of initially high-risk participants with recorded disease indicators decreased over time in both intervention and control groups, being always lower for the intervention group (statistically significant at the 12- and 18-mo time point). In this practice-based clinical trial, a significantly greater percentage of high-caries-risk participants were classified at a lower risk level after CAMBRA preventive therapies were provided. Most participants initially assessed at low caries risk stayed at low risk (ClinicalTrials.gov NCT01176396).

Dental caries is a disease that results from microbiome dysbiosis with the involvement of multiple cariogenic species, including mutans streptococci (MS), lactobacilli, Scardovia wiggsiae, and several Actinomyces species that have the cariogenic traits of acid production and acid tolerance. Sugar consumption also plays an important role interacting with microbiome dysbiosis, determining the fate of caries development. In addition, the MS transmission that encompasses multiple sources can have long-term impacts on the oral microbiome and caries development in children. Intervention in MS transmission in early childhood may promote effective long-term caries prevention. Anticaries regimens aimed against the above mechanisms will be important for successful caries management. Xylitol and erythritol may serve as good components of anticaries regimens as oral microbiome modifiers, sugar substitutes, and agents to prevent MS transmission in early childhood with both oral and systemic benefits. Further studies are needed to elucidate the mechanism of the anticaries effects of xylitol and erythritol with consideration of their impacts on the microbiome and bacterial virulence, in addition to cariogenic bacteria levels as well as their benefits for overall health. On the other hand, the anticaries agent C16G2, specifically targeting Streptococcus mutans, the most common cariogenic bacterial species, has shown good safety for short-term oral topical use and promising effects in reducing S. mutans in vitro and in vivo with the promotion of oral commensal bacteria. Future study on its anticaries effect will need to include its long-term impact on the oral microbiome and effects on other important cariogenic bacteria.

Expanded partnership with the medical community is an important strategy for reducing dental caries disparities. The purpose of this study was to assess the relationship between fluoride (F) "in office" (drops/tablets and/or varnish), as prescribed or applied by a health care professional by age 1 y, and 1) caries development and 2) presence of other caries risk factors or mediators (e.g., socioeconomic status). Child-primary caregiver (PCG) pairs ( N = 1,325) were recruited in Indiana, Iowa, and North Carolina as part of a longitudinal cohort study to validate a caries risk tool for primary health care settings. PCGs completed a caries risk questionnaire, while children received caries examinations per the criteria of the International Caries Detection and Assessment System at ages 1, 2.5, and 4 y. Baseline responses regarding children's history of F in office were tested for association with other caries risk variables and caries experience at ages 2.5 and 4 y via generalized estimating equation models applied to logistic regression. The sample was 48% female, and many children (61%) were Medicaid enrolled. The prevalence of cavitated caries lesions increased from 7% at age 2.5 y to 25% by age 4 y. Children who received F in office were likely deemed at higher caries risk and indeed were significantly ( P < 0.01) more likely to develop cavitated caries lesions by ages 2.5 and 4 y, even after F application (odds ratios: 3.5 and 2.3, respectively). Factors significantly associated with receiving F included the following: child being Medicaid enrolled, not having an employed adult in the household, child and PCG often consuming sugary drinks and snacks, and PCG having recent caries experience. Increased F in office from a health care provider by age 1 y was associated with known caries risk factors. Most (69%) children had never been to the dentist, suggesting that risk factors could be alerting medical providers and/or parents, thereby affecting in-office F recommendations. Differences among states could also be related to state-specific F-varnish reimbursement policies (ClinicalTrials.gov NCT01707797).

Modern approaches in caries treatment involve lesion management without tissue removal. Regenerative medicine focuses on replacing damaged tissues with biologically similar tissues. This article discusses the scientific evidence and clinical results for self-assembling peptides in modern caries management. The biomimetic remineralization promoted by self-assembling peptide P11-4 has been proven in vitro as an effective therapy for initial caries. P11-4 was rationally designed to promote formation of hydroxyapatite on its surface. The formulation was optimized to ensure the ability of monomeric P11-4 to penetrate past the subsurface lesions and assembly into a biomatrix within. Furthermore, P11-4 has shown that it assembles into fibers within carious lesions, and promotes the remineralization thereof. In a recent clinical study, the safety and efficacy of P11-4 in treatment of initial caries were evaluated. The additional effect of the application of P11-4 (Curodont Repair) was compared to the application of fluoride varnish (Duraphat) alone in active occlusal initial caries lesions on erupting permanent molars. In the 3- and 6-month recalls, the test group showed, both in the laser fluorescence readings and in the clinical assessment of the caries stage and activity, significantly superior lesion regression compared to the control group. No adverse events, medical complications, or allergic reactions related to the treatments were reported. Clinical applicability of treatment was regarded as satisfactory. Patients were happy to receive noninvasive caries treatments. In conclusion, biomimetic mineralization facilitated by P11-4 in combination with fluoride may present a simple, safe, and effective noninvasive treatment for early carious lesions.

Silver diamine fluoride (SDF) is a solution containing ionic silver, fluoride, and ammonia that arrests the progress of carious lesions and prevents the development of future caries. The silver particle extends into the dentin tubules and could create some bonding problems for subsequent composite resin restorations placed over SDF-treated darkened tooth structures. The fluoride penetrates deeper into the tooth with SDF as compared with other fluoride solutions, creating a fluoride reservoir in the tooth structure. The fluoride component of SDF contributes to remineralization and fluorapatite formation, producing harder, more caries-resistant tooth structures. The silver provides the antimicrobial activity for the material and inhibits biofilm formation. It has been evaluated in >20 clinical studies and reviewed in systemic reviews. The material was recently approved by the Food and Drug Administration for desensitizing cold-sensitive teeth and has been used off-label to treat carious lesions. SDF will produce a caries lesion darker (brown to black) than the original, which is the major criticism of the material. A nanoparticle-sized silver material was recently developed that may retain the antimicrobial properties of the larger-sized ion silver material without the discoloring effects. The application of SDF is easily adapted for field use. The lesion is isolated, and the solution is painted onto the clean caries lesion and dried. This simple application process requires little equipment, and its low cost per application makes the material ideal for large populations.

A genome-wide transcriptional analysis was performed to elucidate the bacterial cellular response of Streptococcus mutans and Actinomyces viscosus to NaF and SnF₂. The minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) of SnF₂ were predetermined before microarray study. Gene expression profiling microarray experiments were carried out in the absence (control) and presence (experimental) of 10 ppm and 100 ppm Sn²⁺ (in the form of SnF₂) and fluoride controls for 10-min exposures (4 biological replicates/treatment). These Sn²⁺ levels and treatment time were chosen because they have been shown to slow bacterial growth of S. mutans (10 ppm) and A. viscosus (100 ppm) without affecting cell viability. All data generated by microarray experiments were analyzed with bioinformatics tools by applying the following criteria: 1) a q value should be ≤0.05, and 2) an absolute fold change in transcript level should be ≥1.5. Microarray results showed SnF₂ significantly inhibited several genes encoding enzymes of the galactose pathway upon a 10-min exposure versus a negative control: lacA and lacB (A and B subunits of the galactose-6-P isomerase), lacC (tagatose-6-P kinase), lacD (tagatose-1,6-bP adolase), galK (galactokinase), galT (galactose-1-phosphate uridylyltransferase), and galE (UDP-glucose 4-epimerase). A gene fruK encoding fructose-1-phosphate kinase in the fructose pathway was also significantly inhibited. Several genes encoding fructose/mannose-specific enzyme IIABC components in the phosphotransferase system (PTS) were also downregulated, as was ldh encoding lactate dehydrogenase, a key enzyme involved in lactic acid synthesis. SnF₂ downregulated the transcription of most key enzyme genes involved in the galactose pathway and also suppressed several key genes involved in the PTS, which transports sugars into the cell in the first step of glycolysis.

Technological advances in DNA sequencing have provided unprecedented insights into the composition of the oral microbiome in health and disease, and RNA-sequencing and metabolomics-related technologies are beginning to yield information on the activities of these organisms. Importantly, progress in this area has brought the scientific community closer to an understanding of what constitutes a health-associated microbiome and is supporting the notion that the microbiota in healthy sites assumes an active role in promoting health and suppressing the acquisition, persistence, and activities of overt and opportunistic pathogens. It is also becoming clear that a significant impediment to developing a conclusive body of evidence that defines a healthy microbiome and the mechanisms by which beneficial bacteria promote health is that an inherent characteristic of the most abundant members of the oral flora, those that potentially play the greatest roles in health and disease, is intraspecies genomic diversity. In particular, individual isolates of abundant commensal and pathogenic streptococci show tremendous variability in gene content, and this variability manifests in tremendous phenotypic heterogeneity. Analysis of the consequences of this diversity has been complicated by the exquisite sensitivity these bacteria have evolved to environmental inputs, inducing rapid and substantial fluctuations in behaviors, and often only within subpopulations of the organisms. Thus, the conditions under which the oral microbiota is studied can produce widely different results within and between species. Fortunately, continually diminishing costs and ongoing refinements in sequencing and metabolomics are making it practical to study the oral microbiome at a level that will create a sufficiently robust understanding of the functions of individual organisms and reveal the complex interrelationships of these microbes ("the known unknowns") in a way that researchers will be able to engage in the rational design of reliable and economical risk assessments and preventive therapies.