Showing papers in "Journal of Dental Research in 2018"

Novel Zirconia Materials in Dentistry

Abstract: Zirconias, the strongest of the dental ceramics, are increasingly being fabricated in monolithic form for a range of clinical applications. Y-TZP (yttria-stabilized tetragonal zirconia polycrystal) is the most widely used variant. However, current Y-TZP ceramics on the market lack the aesthetics of competitive glass-ceramics and are therefore somewhat restricted in the anterior region. This article reviews the progressive development of currently available and next-generation zirconias, representing a concerted drive toward greater translucency while preserving adequate strength and toughness. Limitations of efforts directed toward this end are examined, such as reducing the content of light-scattering alumina sintering aid or incorporating a component of optically isotropic cubic phase into the tetragonal structure. The latest fabrication routes based on refined starting powders and dopants, with innovative sintering protocols and associated surface treatments, are described. The need to understand the several, often complex, mechanisms of long-term failure in relation to routine laboratory test data is presented as a vital step in bridging the gaps among material scientist, dental manufacturer, and clinical provider.

Global-, Regional-, and Country-Level Economic Impacts of Dental Diseases in 2015:

Abstract: Up-to-date information about the economic impact of dental diseases is essential for health care decision makers when seeking to make rational use of available resources. The purpose of this study was to provide up-to-date estimates for dental expenditures (direct costs) and productivity losses (indirect costs) due to dental diseases on the global, regional, and country level. Direct costs of dental diseases were estimated using a previously established systematic approach; indirect costs were estimated using an approach developed by the World Health Organization Commission on Macroeconomics and Health and factoring in 2015 values for gross domestic product and disability-adjusted life years from the Global Burden of Disease Study. The estimated direct costs of dental diseases amounted to $356.80 billion and indirect costs were estimated at $187.61 billion, totaling worldwide costs due to dental diseases of $544.41 billion in 2015. After adjustment for purchasing power parity, the highest levels of per capita dental expenditures were found for High-Income North America, Australasia, Western Europe, High-Income Asia Pacific, and East Asia; the highest levels of per capita productivity losses were found for Western Europe, Australasia, High-Income North America, High-Income Asia Pacific, and Central Europe. Severe tooth loss was found to imply 67% of global productivity losses due to dental diseases, followed by severe periodontitis (21%) and untreated caries (12%). From an economic perspective, improvements in population oral health may be highly beneficial and could contribute to further increases in people's well-being given available resources.

Trends in Dental Implant Use in the U.S., 1999–2016, and Projections to 2026:

Abstract: Dental implants have become an increasingly popular treatment choice for replacing missing teeth. Yet, little is known about the prevalence and sociodemographic distribution of dental implant use in the United States. To address this knowledge gap, we analyzed data from 7 National Health and Nutrition Examination Surveys from 1999 to 2016. We estimated dental implant prevalence among adults missing any teeth for each survey period overall as stratified by sociodemographic characteristics. We calculated absolute and relative differences from 1999-2000 to 2015-2016 and fit logistic regression models to estimate changes over time. We also used multivariable logistic regression to estimate independent associations of sociodemographic covariates with the presence of any implant. We projected the proportion of patients treated with dental implants into the year 2026 under varying assumptions of how the temporal trend would continue. There has been a large increase in the prevalence of dental implants, from 0.7% in 1999 to 2000 to 5.7% in 2015 to 2016. The largest absolute increase in prevalence (12.9%) was among individuals 65 to 74 y old, whereas the largest relative increase was ~1,000% among those 55 to 64 y old. There was an average covariate-adjusted increase in dental implant prevalence of 14% per year (95% CI, 11% to 18%). Having private insurance (vs. none or public insurance) or more than a high school education (vs. high school or less) was each associated with a 2-fold increase in prevalence, with an almost 13-fold (95% CI, 8 to21) increase for older adults. Dental implant prevalence projected to 2026 ranged from 5.7% in the most conservative scenario to 23% in the least. This study demonstrates that dental implant prevalence among US adults with missing teeth has substantially increased since 1999. Yet access overall is still very low, and prevalence was consistently higher among more advantaged groups.

Resilience of the Oral Microbiota in Health: Mechanisms That Prevent Dysbiosis:

Abstract: Dental diseases are now viewed as a consequence of a deleterious shift in the balance of the normally stable resident oral microbiome. It is known that frequent carbohydrate consumption or reduced saliva flow can lead to caries, and excessive plaque accumulation increases the risk of periodontal diseases. However, when these "disease drivers" are present, while some individuals appear to be susceptible, others are more tolerant or resilient to suffering from undesirable changes in their oral microbiome. Health-maintaining mechanisms that limit the effect of disease drivers include the complex set of metabolic and functional interrelationships that develop within dental biofilms and between biofilms and the host. In contrast, "positive feedback loops" can develop within these microbial communities that disrupt resilience and provoke a large and abrupt change in function and structure of the ecosystem (a microbial "regime shift"), which promotes dysbiosis and oral disease. For instance, acidification due to carbohydrate fermentation or inflammation in response to accumulated plaque select for a cariogenic or periopathogenic microbiota, respectively, in a chain of self-reinforcing events. Conversely, in tolerant individuals, health-maintaining mechanisms, including negative feedback to the drivers, can maintain resilience and promote resistance to and recovery from disease drivers. Recently studied health-maintaining mechanisms include ammonia production, limiting a drop in pH that can lead to caries, and denitrification, which could inhibit several stages of disease-associated positive feedback loops. Omics studies comparing the microbiome of, and its interaction with, susceptible and tolerant hosts can detect markers of resilience. The neutralization or inhibition of disease drivers, together with the identification and promotion of health-promoting species and functions, for example, by pre- and probiotics, could enhance microbiome resilience and lead to new strategies to prevent disease.

CAD/CAM Ceramic Restorative Materials for Natural Teeth.

Abstract: Advances in computer-aided design (CAD) / computer-aided manufacturing (CAM) technologies and their ease of application enabled the development of novel treatment concepts for modern prosthodontics. This recent paradigm shift in fixed prosthodontics from traditional to minimally invasive treatment approaches is evidenced by the clinical long-term success of bonded CAD/CAM glass-ceramic restorations. Today, defect-oriented restorations, such as inlays, onlays, and posterior crowns, are predominately fabricated from glass-ceramics in monolithic application. The variety of CAD/CAM ceramic restorative systems is constantly evolving to meet the increased demands for highly aesthetic, biocompatible, and long-lasting restorations. Recently introduced polymer-infiltrated ceramic network CAD/CAM blocks add innovative treatment options in CAD/CAM chairside 1-visit restorations. The material-specific high-edge stability enables the CAD/CAM machinability of thin restoration margins. Full-contour zirconia restorations are constantly gaining market share at the expense of bilayered systems. Advancements in material science and bonding protocols foster the development of novel material combinations or fabrication techniques of proven high-strength zirconia ceramics. CAD/CAM applications offer a standardized manufacturing process resulting in a reliable, predictable, and economic workflow for individual and complex teeth-supported restorations. More evidence from long-term clinical studies is needed to verify the clinical performance of monolithic polymer-infiltrated ceramic network and zirconia teeth-supported minimally invasive and extensive restorations.

The Effect of Resin Bonding on Long-Term Success of High-Strength Ceramics.

Abstract: Digital manufacturing, all-ceramics, and adhesive dentistry are currently the trendiest topics in clinical restorative dentistry. Tooth- and implant-supported fixed restorations from computer-aided design (CAD)/computer-aided manufacturing (CAM)-fabricated high-strength ceramics-namely, alumina and zirconia-are widely accepted as reliable alternatives to traditional metal-ceramic restorations. Most recent developments have focused on high-translucent monolithic full-contour zirconia restorations, which have become extremely popular in a short period of time, due to physical strength, CAD/CAM fabrication, and low cost. However, questions about proper resin bonding protocols have emerged, as they are critical for clinical success of brittle ceramics and treatment options that rely on adhesive bonds, specifically resin-bonded fixed dental prostheses or partial-coverage restorations such as inlays/onlays and veneers. Resin bonding has long been the gold standard for retention and reinforcement of low- to medium-strength silica-based ceramics but requires multiple pretreatment steps of the bonding surfaces, increasing complexity, and technique sensitivity compared to conventional cementation. Here, we critically review and discuss the evidence on resin bonding related to long-term clinical outcomes of tooth- and implant-supported high-strength ceramic restorations. Based on a targeted literature search, clinical long-term studies indicate that porcelain-veneered alumina or zirconia full-coverage crowns and fixed dental prostheses have high long-term survival rates when inserted with conventional cements. However, most of the selected studies recommend resin bonding and suggest even greater success with composite resins or self-adhesive resin cements, especially for implant-supported restorations. High-strength ceramic resin-bonded fixed dental prostheses have high long-term clinical success rates, especially when designed as a cantilever with only 1 retainer. Proper pretreatment of the bonding surfaces and application of primers or composite resins that contain special adhesive monomers are necessary. To date, there are no clinical long-term data on resin bonding of partial-coverage high-strength ceramic or monolithic zirconia restorations.

Arresting Dentine Caries with Silver Diamine Fluoride: What's Behind It?

Abstract: Unlike other fluoride-based caries preventive agents, silver diamine fluoride (SDF) can simultaneously prevent and arrest coronal and root dentine caries. The profound clinical success of SDF has drawn many clinicians and researchers to study the mechanism of SDF in arresting dentine caries. This critical review discusses how silver and fluoride contribute to caries arrest, in terms of their effects on bacteria as well as on the mineral and organic content of dentine. Silver interacts with bacterial cell membrane and bacterial enzymes, which can inhibit bacterial growth. Silver can also dope into hydroxyapatite and have an antibacterial effect on silver-doped hydroxyapatite. Furthermore, silver is also a strong inhibitor of cathepsins and inhibits dentine collagen degradation. Early studies proposed that silver hardened caries lesions by forming silver phosphate. However, recent studies found that little silver phosphate remained on the arrested dentine lesion. The principal silver precipitate was silver chloride, which could not contribute to the significant hardening of the arrested lesions. On the other hand, fluoride enhances mineral formation by forming fluorohydroxyapatite with reduced solubility. A significant increase in microhardness occurs with an elevated level of calcium and phosphorus but not silver on the surface layer of the arrested dentine caries lesion following SDF treatment. Fluoride also inhibits matrix metalloproteinases activities and therefore inhibits dentine collagen degradation. The combination of silver and fluoride in an alkaline solution has a synergistic effect in arresting dentine caries. The alkaline property of SDF provides an unfavorable environment for collagen enzyme activation. Understanding the mechanisms of SDF in arresting dentine caries helps clinicians to develop appropriate protocols for the use of SDF in clinical care.

Is Metal Particle Release Associated with Peri-implant Bone Destruction? An Emerging Concept:

Abstract: Peri-implant diseases affecting the surrounding structures of endosseous dental implants include peri-implant mucositis and peri-implantitis. The prevalence of peri-implantitis ranges between 15% and 20% after 10 y, highlighting the major challenge in clinical practice in the rehabilitation of dental implant patients. The widespread nature of peri-implant bone loss poses difficulties in the management of biological complications affecting the long-term success of osseointegrated implant reconstructions. Metal and titanium particles have been detected in peri-implant supporting tissues. However, it remains unclear what mechanisms could be responsible for the elicitation of particle and ion release and whether these released implant-associated materials have a local and/or systemic impact on the peri-implant soft and hard tissues. Metal particle release as a potential etiologic factor has been intensively studied in the field of orthopedics and is known to provoke aseptic loosening around arthroplasties and is associated with implant failures. In dental medicine, emerging information about metal/titanium particle release suggests that the potential impact of biomaterials at the abutment or bone interfaces may have an influence on the pathogenesis of peri-implant bone loss. This mini-review highlights current evidence of metal particle release around dental implants and future areas for research.

Randomized Clinical Trial of 12% and 38% Silver Diamine Fluoride Treatment.

Abstract: This 30-mo randomized clinical trial compared the effectiveness of 2 concentrations (12% or 38%) of silver diamine fluoride (SDF) and 2 periodicity of application (once or twice a year) in arresting cavitated dentin caries in primary teeth. Children aged 3 to 4 y who had at least 1 active cavitated caries lesion were enrolled and randomly allocated into 4 groups for intervention. Group 1 had 12% SDF applied annually (every 12 mo), group 2 had 12% SDF applied semiannually (every 6 mo), group 3 had 38% SDF applied annually, and group 4 had 38% SDF applied semiannually. Clinical examinations were performed semiannually in kindergarten by a single examiner to investigate whether the SDF-treated caries became arrested. A total of 888 children with 4,220 decayed tooth surfaces received SDF application at baseline, and 799 (90.0%) children with 3,790 surfaces (89.8%) were evaluated at the 30-mo examination. The caries arrest rates were 55.2%, 58.6%, 66.9%, and 75.7% for groups 1, 2, 3, and 4, respectively ( P < 0.001). Caries treated with 38% SDF had a higher chance of becoming arrested than those treated with 12% SDF (odds ratio [OR], 1.98; 95% confidence interval [CI], 1.51-2.60, P < 0.001). The interaction between frequency of SDF application and visible plaque index (VPI) score was significant ( P = 0.017). Among those children who received annual SDF application, children with a higher VPI score had a lower chance to have their caries become arrested (OR, 0.59, 95% CI, 0.49-0.72). In conclusion, SDF at a concentration of 38% is more effective than that of 12% in arresting active caries in primary teeth. For children with poor oral hygiene, caries arrest rate of SDF treatment can be increased by increasing the frequency of application from annually to semiannually ( ClinicalTrials.gov NCT02385474).

Effectiveness of Contour Augmentation with Guided Bone Regeneration: 10-Year Results.

Abstract: In aesthetic sites, the integrity of the facial bone wall dimension in the anterior maxilla is jeopardized by physiologic and structural changes postextraction. An effective regenerative protocol is key to reestablish and maintain the hard and soft tissue dimensions over time. The present prospective case series study examined the effectiveness of early implant placement with simultaneous contour augmentation through guided bone regeneration with a 2-layer composite graft in postextraction single-tooth sites over an observation period of 10 y among 20 patients. The median peri-implant bone loss was 0.35 mm between the 1- and 10-y examination. A success rate of 95% was obtained, with pleasing aesthetic outcomes and a high median Pink Esthetic Score (8). Implant crowns (ICs) revealed significant median facial recession between IC10y and IC1y (0.17 mm). The facial bone wall dimensions were assessed by preoperative cone beam computed tomography and 2 subsequent scans taken at 6 and 10 y. The median facial bone wall thickness increased significantly from 0 mm at surgery to 1.67 mm at the 10-y examination. The facial vertical bone wall peak (DIC) was located at a median distance of 0.16 mm coronal to the implant shoulder. The facial vertical bone loss of DIC amounted to 0.02 mm between 6 and 10 y. Equivalence testing was performed for the null hypothesis of a difference of >0.2 mm per year between 2 respective time points, showing stable bone conditions. Modulating factors influencing the regenerative outcomes at 10 y were the preoperative proximal crest width and soft tissue thickness. In conclusion, the present study confirmed the long-term effectiveness of early implant placement with simultaneous contour augmentation through guided bone regeneration with a 2-layer composite graft in postextraction single-tooth sites offering stable bone conditions with low risks of mucosal recessions over an observation period of 10 y ( ClinicalTrials.gov NCT03252106).

Inflammatory Bacteriome and Oral Squamous Cell Carcinoma

Abstract: Results from microbiome studies on oral cancer have been inconsistent, probably because they focused on compositional analysis, which does not account for functional redundancy among oral bacteria. Based on functional prediction, a recent study revealed enrichment of inflammatory bacterial attributes in oral squamous cell carcinoma (OSCC). Given the high relevance of this finding to carcinogenesis, we aimed here to corroborate them in a case-control study involving 25 OSCC cases and 27 fibroepithelial polyp (FEP) controls from Sri Lanka. DNA extracted from fresh biopsies was sequenced for the V1 to V3 region with Illumina's 2 × 300-bp chemistry. High-quality nonchimeric merged reads were classified to the species level with a prioritized BLASTN-based algorithm. Downstream compositional analysis was performed with QIIME (Quantitative Insights into Microbial Ecology) and linear discriminant analysis effect size, while PICRUSt (Phylogenetic Investigation of Communities by Reconstruction of Unobserved States) was utilized for bacteriome functional prediction. The OSCC tissues tended to have lower species richness and diversity. Genera Capnocytophaga, Pseudomonas, and Atopobium were overrepresented in OSCC, while Lautropia, Staphylococcus, and Propionibacterium were the most abundant in FEP. At the species level, Campylobacter concisus, Prevotella salivae, Prevotella loeschii, and Fusobacterium oral taxon 204 were enriched in OSCC, while Streptococcus mitis, Streptococcus oral taxon 070, Lautropia mirabilis, and Rothia dentocariosa among others were more abundant in FEP. Functionally, proinflammatory bacterial attributes, including lipopolysaccharide biosynthesis and peptidases, were enriched in the OSCC tissues. Thus, while the results in terms of species composition significantly differed from the original study, they were consistent at the functional level, substantiating evidence for the inflammatory nature of the bacteriome associated with OSCC.

Pulp Regeneration by 3-dimensional Dental Pulp Stem Cell Constructs.

Abstract: Dental pulp regeneration therapy for the pulpless tooth has attracted recent attention, and clinical trial studies are underway with the tissue engineering approach. However, there remain many concerns, including the extended period for regenerating the dental pulp. In addition, the use of scaffolds increases the risk of inflammation and infection. To establish a basic technology for novel dental pulp regenerative therapy that allows transplant of pulp-like tissue, we attempted to fabricate scaffold-free 3-dimensional (3D) cell constructs composed of dental pulp stem cells (DPSCs). Furthermore, we assessed viability of these 3D DPSC constructs for dental pulp regeneration through in vitro and in vivo studies. For the in vitro study, we obtained 3D DPSC constructs by shaping sheet-like aggregates of DPSCs with a thermoresponsive hydrogel. DPSCs within constructs remained viable even after prolonged culture; furthermore, 3D DPSC constructs possessed a self-organization ability necessary to serve as a transplant tissue. For the in vivo study, we filled the human tooth root canal with DPSC constructs and implanted it subcutaneously into immunodeficient mice. We found that pulp-like tissues with rich blood vessels were formed within the human root canal 6 wk after implantation. Histologic analyses revealed that transplanted DPSCs differentiated into odontoblast-like mineralizing cells at sites in contact with dentin; furthermore, human CD31-positive endothelial cells were found at the center of regenerated tissue. Thus, the self-organizing ability of 3D DPSC constructs was active within the pulpless root canal in vivo. In addition, blood vessel-rich pulp-like tissues can be formed with DPSCs without requiring scaffolds or growth factors. The technology established in this study allows us to prepare DPSC constructs with variable sizes and shapes; therefore, transplantation of DPSC constructs shows promise for regeneration of pulpal tissue in the pulpless tooth.

Emerging Role of Extracellular Vesicles in Bone Remodeling.

Abstract: Extracellular vesicles (EVs), as nanometer-scale particles, include exosomes, microvesicles, and apoptotic bodies. EVs are released by most cell types, such as bone marrow stem cells, osteoblasts, osteoclasts, and immune cells. In bone-remodeling microenvironments, EVs deliver specific proteins (e.g., tenascin C and Sema4D), microRNAs (e.g., miR-214-3p, miR-183-5p, and miR-196a), and other growth factors (e.g., bone morphogenetic protein 1 to 7 and transforming growth factor β1) to osteoblasts and regulate bone formation. In addition, EVs can deliver cytokines, such as RANK (receptor activator of nuclear factor κB) and RANKL (RANK ligand), and microRNAs, such as miR-218 and miR-148a, to modulate osteoclast differentiation during bone resorption. EVs also transfer bioactive molecules and have targeted therapies in bone-related diseases. Moreover, bioactive molecules in EVs are biomarkers in bone-related diseases. We highlight the emerging role of EVs in bone remodeling during physiologic and pathologic conditions and summarize the role of EVs in tooth development and regeneration. At the end of this review, we discuss the challenges of EV application in the treatment of bone diseases.

Custom Repair of Mandibular Bone Defects with 3D Printed Bioceramic Scaffolds.

Abstract: Implanting artificial biomaterial implants into alveolar bone defects with individual shape and appropriate mechanical strength is still a challenge. In this study, bioceramic scaffolds, which can ...

Association between Oral Candida and Bacteriome in Children with Severe ECC

Abstract: Candida albicans is an opportunistic fungal organism frequently detected in the oral cavity of children with severe early childhood caries (S-ECC). Previous studies suggested the cariogenic potential of C. albicans, in vitro and in vivo, and further demonstrated its synergistic interactions with Streptococcus mutans. In combination, the 2 organisms are associated with higher caries severity in a rodent model. However, it remains unknown whether C. albicans influences the composition and diversity of the entire oral bacterial community to promote S-ECC onset. With 16s rRNA amplicon sequencing, this study analyzed the microbiota of saliva and supragingival plaque from 39 children (21 S-ECC and 18 caries-free [CF]) and 33 mothers (17 S-ECC and 16 CF). The results revealed that the presence of oral C. albicans is associated with a highly acidogenic and acid-tolerant bacterial community in S-ECC, with an increased abundance of plaque Streptococcus (particularly S. mutans) and certain Lactobacillus/Scardovia species and salivary/plaque Veillonella and Prevotella, as well as decreased levels of salivary/plaque Actinomyces. Concurrent with this microbial community assembly, the activity of glucosyltransferases (cariogenic virulence factors secreted by S. mutans) in plaque was significantly elevated when C. albicans was present. Moreover, the oral microbial community composition and diversity differed significantly by disease group (CF vs. S-ECC) and sample source (saliva vs. plaque). Children and mothers within the CF and S-ECC groups shared microbiota composition and diversity, suggesting a strong maternal influence on children's oral microbiota. Altogether, this study underscores the importance of C. albicans in association with the oral bacteriome in the context of S-ECC etiopathogenesis. Further longitudinal studies are warranted to examine how fungal-bacterial interactions modulate the onset and severity of S-ECC, potentially leading to novel anticaries treatments that address fungal contributions.

Perineural Invasion in Head and Neck Cancer

Abstract: Perineural invasion (PNI) is a mechanism of tumor dissemination that can provide a challenge to tumor eradication and that is correlated with poor survival. Squamous cell carcinoma, the most common type of head and neck cancer, has a high prevalence of PNI. This review provides an overview of clinical studies on the outcomes and factors associated with PNI in head and neck cancer and on findings on cancer-nerve crosstalk.

Liquid Biopsy in Head and Neck Cancer: Promises and Challenges.

Abstract: Head and neck cancer is the sixth most common cancer worldwide. It remains one of the leading causes of death, and its early detection is crucial. Liquid biopsy has emerged as a promising tool for detecting and monitoring the disease status of patients with early and advanced cancers. Circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), and exosomal miRNAs have received enormous attention because of their apparent clinical implications. Analyses of these circulating biomarkers have paved the way for novel therapeutic approaches and precision medicine. A growing number of reports have implicated the use of circulating biomarkers for detection, treatment planning, response monitoring, and prognosis assessment. Although these new biomarkers can provide a wide range of possible clinical applications, no validated circulating biomarkers have yet been integrated into clinical practice for head and neck cancer. In this review, we summarize the current knowledge of circulating biomarkers in this field, focusing on their feasibility, limitations, and key areas of clinical applications. We also highlight recent advances in salivary diagnostics and their potential application in head and neck cancer.

Targeting the DNA Damage Response in OSCC with TP53 Mutations.

Abstract: Oral squamous cell carcinoma (OSCC) is the most common type of oral cancer worldwide and in the United States. OSCC remains a major cause of morbidity and mortality in patients with head and neck cancers. Tobacco and alcohol consumption alone or with chewing betel nut are potential risk factors contributing to the high prevalence of OSCC. Multimodality therapies, including surgery, chemotherapy, biologic therapy, and radiotherapy, particularly intensity-modulated radiotherapy (IMRT), are the current treatments for OSCC patients. Despite recent advances in these treatment modalities, the overall survival remains poor over the past years. Recent data from whole-exome sequencing reveal that TP53 is commonly mutated in human papillomavirus-negative OSCC patients. Furthermore, these data stressed the importance of the TP53 gene in suppressing the development and progression of OSCC. Clinically, TP53 mutations are largely associated with poor survival and tumor resistance to radiotherapy and chemotherapy in OSCC patients, which makes the TP53 mutation status a potentially useful molecular marker prognostic and predictive of clinical response in these patients. Several forms of DNA damage have been shown to activate p53, including those generated by ionizing radiation and chemotherapy. The DNA damage stabilizes p53 in part via the DNA damage signaling pathway that involves sensor kinases, including ATM and ATR and effector kinases, such as Chk1/2 and Wee1, which leads to posttranscriptional regulation of a variety of genes involved in DNA repair, cell cycle control, apoptosis, and senescence. Here, we discuss the link of TP53 mutations with treatment outcome and survival in OSCC patients. We also provide evidence that small-molecule inhibitors of critical proteins that regulate DNA damage repair and replication stress during the cell cycle progression, as well as other molecules that restore wild-type p53 activity to mutant p53, can be exploited as novel therapeutic approaches for the treatment of OSCC patients bearing p53 mutant tumors.

Self-assembling Peptide P11-4 and Fluoride for Regenerating Enamel:

Abstract: Regenerative medicine-based approaches for caries treatment focus on biomimetic remineralization of initial carious lesions as a minimal invasive therapy. In vitro, self-assembling peptide P11-4 enhances remineralization of early carious lesions. To investigate the safety and clinical efficacy of P11-4 for treatment of initial caries, a randomized controlled single-blind study was conducted on children aged >5 y with visible active early caries on erupting permanent molars. Subjects were randomized to either the test group (P11-4 + fluoride varnish) or control group (fluoride varnish alone). Caries were assessed at baseline and at 3 and 6 mo posttreatment per laser fluorescence, a visual analog scale, the International Caries Detection and Assessment System, and Nyvad caries activity criteria. Intention-to-treat analyses were performed, and safety and clinical feasibility of the treatment approaches were assessed. Compared with the control group, the test group showed clinically and statistically significant improvement in all outcomes at 3 and 6 mo. The laser fluorescence readings (odds ratio = 3.5, P = 0.015) and visual analog scale scores (odds ratio = 7.9, P < .0001) were significantly lower for the test group, and they showed regression in the International Caries Detection and Assessment System caries index (odds ratio = 5.1, P = 0.018) and conversion from active to inactive lesions according to Nyvad criteria (odds ratio = 12.2, P < 0.0001). No adverse events occurred. The biomimetic mineralization facilitated by P11-4 in combination with fluoride application is a simple, safe, and effective noninvasive treatment for early carious lesions that is superior to the presently used gold standard of fluoride alone. By regenerating enamel tissue and preventing lesion progression, this novel approach could change clinical dental practice from a restorative to a therapeutic approach. This could avoid additional loss of healthy hard tissue during invasive restorative treatments, potentially enabling longer tooth life and thereby lowering long-term health costs ( ClinicalTrials.gov NCT02724592).

Graded Ultra-Translucent Zirconia (5Y-PSZ) for Strength and Functionalities.

Abstract: Ultra-translucent zirconias are drawing immense attention due to their fascinating esthetic appearance. However, the high translucency came at the expense of diminishing strength along with the reduced ability of transformation toughening due to the increased cubic zirconia content. We aim to address these issues by infiltrating glass on the surface of an ultra-translucent zirconia (5Y-PSZ). Glasses of different shades can be used and the resulting graded glass/zirconia layer is expected to improve the material's flexural strength without compromising its esthetics. We also aim to elucidate how clinically relevant surface treatments-namely, air abrasion, glazing, or polishing-affect the fracture resistance of these zirconias with a high cubic content. All surface treatments were performed on bar-shaped (2 × 3 × 25 mm3) and plate-shaped (12 × 12 × 1 mm3) specimens, which were then subjected to a 4-point bending test and translucency measurements, respectively. 5Y-PSZ proved to be significantly more translucent than 3Y-TZP but also much weaker. Our hypothesis was accepted, as the strength of the glass-infiltrated ultra-translucent 5Y-PSZ (582 ± 20 MPa) is over 70% higher than its uninfiltrated counterpart (324 ± 57 MPa). Its strength is also over 25% higher than the highly polished 5Y-PSZ (467 ± 38 MPa). In addition, the translucency of 5Y-PSZ (translucency parameter [ TP] = 34, contrast ratio [ CR] = 0.31) is not affected by glass infiltration ( TP = 34, CR = 0.32) when the residual surface glass is removed by gentle polishing using 6- and then 3-µm diamond grits. Finally, both air abrasion and the presence of a glaze layer on the tensile surface decreased flexural strength significantly, being 274 ± 55 and 211 ± 21 MPa, respectively. With a combined high strength and translucency, the newly developed glass-infiltrated 5Y-PSZ may be considered a suitable material for next-generation, damage-resistant, and esthetic dental restorations.

Adverse Effects of Silver Diamine Fluoride Treatment among Preschool Children.

Abstract: This randomized clinical trial aimed to compare the adverse effects and parental satisfaction following the different regimes of silver diamine fluoride (SDF) treatment among preschool children. A total of 888 preschool children who had active dentin caries received different SDF application regimes: group 1, 12% SDF applied annually; group 2, 12% SDF applied semiannually; group 3, 38% SDF applied annually; and group 4, 38% SDF applied semiannually. Information on adverse effects-including tooth or gum pain, gum swelling, gum bleaching, and systemic toxicity-was collected through a parent-reported questionnaire within 1 wk after every SDF or placebo application. Information of parental satisfaction on children's dental appearance was collected at baseline and 30-mo examination. At the 30 mo, 799 children (90%) remained in the study. No acute systemic illness or major adverse effect was reported. No differences of all minor adverse effects among the 4 groups were found ( P > 0.05). Overall, prevalence of tooth and gum pain as perceived by patients and reported by parents was 6.6%, while gum swelling and gum bleaching were 2.8% and 4.7%, respectively. Blackening of carious lesions was common among all groups, with 36.7%, 49.5%, 65.6% and 76.3% in groups 1 to 4, respectively (χ2 test, P 0.05). Based on parental reporting, SDF does not cause acute systemic illness. Tooth or gum pain, gum swelling, and gum bleaching were uncommon and not significantly different among the study groups. Parental satisfaction with children's dental appearance was similar among all groups. The use of SDF following the study protocol for caries arrest is safe for preschool children. Collecting information on parental satisfaction and adverse effects is beneficial for dental professionals when deciding to adopt SDF treatment for preschool children (ClinicalTrials.gov NCT02385474).

Metatranscriptome of the Oral Microbiome in Health and Disease.

Abstract: The last few decades have witnessed an increasing interest in studying the human microbiome and its role in health and disease. The focus of those studies was mainly the characterization of changes in the composition of the microbial communities under different conditions. As a result of those studies, we now know that imbalance in the composition of the microbiome, also referred to as microbial dysbiosis, is directly linked to developing certain conditions. Dysbiosis of the oral microbiome is a prime example of how this imbalance leads to disease in the case of periodontal disease. However, there is considerable overlap in the phylogenetic profiles of microbial communities associated with active and inactive lesions, suggesting that the difference in periodontal status of those sites may not be explained solely by differences in the subgingival microbial composition. These findings suggest that differences in functional activities may be the essential elements that define the dysbiotic process. Researchers have recently begun to study gene expression of the oral microbiome in situ with the goal of identifying changes in functional activities that could explain the transition from health to disease. These initial results suggest that, rather than a specific composition, a better understanding of oral dysbiosis can be obtained from the study of functional activities of the microbial community. In this review, we give a summary of these initial studies, which have opened a new door to our understanding of the dynamics of the oral community during the dysbiotic process in the oral cavity.

Chitosan-Based Trilayer Scaffold for Multitissue Periodontal Regeneration:

Abstract: Periodontal regeneration is still a challenge for periodontists and tissue engineers, as it requires the simultaneous restoration of different tissues-namely, cementum, gingiva, bone, and periodontal ligament (PDL). Here, we synthetized a chitosan (CH)-based trilayer porous scaffold to achieve periodontal regeneration driven by multitissue simultaneous healing. We produced 2 porous compartments for bone and gingiva regeneration by cross-linking with genipin either medium molecular weight (MMW) or low molecular weight (LMW) CH and freeze-drying the resulting scaffolds. We synthetized a third compartment for PDL regeneration by CH electrochemical deposition; this allowed us to produce highly oriented microchannels of about 450-µm diameter intended to drive PDL fiber growth toward the dental root. In vitro characterization showed rapid equilibrium water content for MMW-CH and LMW-CH compartments (equilibrium water content after 5 min >85%). The MMW-CH compartment degraded more slowly and provided significantly more resistance to compression (28% ± 1% of weight loss at 4 wk; compression modulus HA = 18 ± 6 kPa) than the LMW-CH compartment (34% ± 1%; 7.7 ± 0.8 kPa) as required to match the physiologic healing rates of bone and gingiva and their mechanical properties. More than 90% of all human primary periodontal cell populations tested on the corresponding compartment survived during cytocompatibility tests, showing active cell metabolism in the alkaline phosphatase and collagen deposition assays. In vivo tests showed high biocompatibility in wild-type mice, tissue ingrowth, and vascularization within the scaffold. Using the periodontal ectopic model in nude mice, we preseeded scaffold compartments with human gingival fibroblasts, osteoblasts, and PDL fibroblasts and found a dense mineralized matrix within the MMW-CH region, with weakly mineralized deposits at the dentin interface. Together, these results support this resorbable trilayer scaffold as a promising candidate for periodontal regeneration.

Etching Efficacy of Self-Etching Functional Monomers.

Abstract: Besides chemically interacting with hard tooth tissue, acidic functional monomers of self-etch adhesives should etch the prepared tooth surface to dissolve the smear layer and to provide surface micro-retention. Although the etching efficacy of functional monomers is commonly determined in terms of pH, the pH of adhesives cannot accurately be measured. Better is to measure the hydroxyapatite (HAp)-dissolving capacity, also considering that functional monomers may form monomer-Ca salts. Here, the etching efficacy of 6 functional monomers (GPDM, phenyl-P, MTEGP, 4-META, 6-MHP and 10-MDP) was investigated. Solutions containing 15 wt% monomer, 45 wt% ethanol, and 40 wt% water were prepared. Initially, we observed enamel surfaces exposed to monomer solution by scanning electron microscopy (SEM). X-ray diffraction (XRD) was employed to detect monomer-Ca salt formation. Phenyl-P exhibited a strong etching effect, while 10-MDP-treated enamel showed substance deposition, which was identified by XRD as 10-MDP-Ca salt. To confirm these SEM/XRD findings, we determined the etching efficacy of functional monomers by measuring both the concentration of Ca released from HAp using inductively coupled plasma-atomic emission spectroscopy (ICP-AES) and the amount of monomer-Ca salt formation using 31P magic-angle spinning (MAS) nuclear magnetic resonance (NMR). ICP-AES revealed that the highest Ca concentration was produced by phenyl-P and the lowest Ca concentration, almost equally, by 4-META and 10-MDP. Only 10-MDP formed 10-MDP-Ca salts, indicating that 10-MDP released more Ca from HAp than was measured by ICP-AES. Part of the released Ca was consumed to form 10-MDP-Ca salts. It is concluded that the repeatedly reported higher bonding effectiveness of 10-MDP-based adhesives must not only be attributed to the more intense chemical bonding of 10-MDP but also to its higher etching potential, a combination the other functional monomers investigated lack.

The NOTCH Pathway in Head and Neck Squamous Cell Carcinoma.

Abstract: Comprehensive genomic analyses have been performed for head and neck squamous cell carcinoma (HNSCC), revealing a significant rate of NOTCH1 mutations and identifying NOTCH1 as the second most frequently mutated gene after TP53. Most NOTCH1 mutations are considered inactivating, indicating that NOTCH1 is a tumor suppressor gene. On the other hand, cohorts from Asian populations with HNSCC have shown activating NOTCH1 mutations. HNSCC with NOTCH1 mutations have a worse prognosis than the NOTCH1 wild-type tumors. Additional data on other NOTCH family members have shown that NOTCH promotes HNSCC progression. NOTCH family members, including NOTCH pathway genes, are upregulated in HNSCC compared with normal tissues, and inhibition of the NOTCH pathway decreases cell proliferation and invasion. NOTCH activity in HNSCC is therefore contextual, and NOTCH in HNSCC is considered to have a bimodal role as a tumor suppressor and an oncogene. In this review, recent understandings of NOTCH pathway genes, including NOTCH genes, in HNSCC are described. In addition, the implications of NOTCH pathway alteration for HNSCC-specific NOTCH-targeted cancer therapy are explored.

A Wnt-Responsive PDL Population Effectuates Extraction Socket Healing

Abstract: Stem cells residing in the periodontal ligament (PDL) support the homeostasis of the periodontium, but their in vivo identity, source(s), and function(s) remain poorly understood. Here, using a lineage-tracing mouse strain, we identified a quiescent Wnt-responsive population in the PDL that became activated in response to tooth extraction. The Wnt-responsive population expanded by proliferation, then migrated from the PDL remnants that remained attached to bundle bone, into the socket. Once there, the Wnt-responsive progeny upregulated osteogenic protein expression, differentiated into osteoblasts, and generated the new bone that healed the socket. Using a liposomal WNT3A protein therapeutic, we showed that a single application at the time of extraction was sufficient to accelerate extraction socket healing 2-fold. Collectively, these data identify a new stem cell population in the intact periodontium that is directly responsible for alveolar bone healing after tooth removal.

Dysbiotic Biofilms Deregulate the Periodontal Inflammatory Response.

Abstract: Periodontal diseases originate from a dysbiosis within the oral microbiota, which is associated with a deregulation of the host immune response. Although little is known about the initiation of dysbiosis, it has been shown that H2O2 production is one of the main mechanisms by which some commensal bacteria suppress the outgrowth of pathobionts. Current models emphasize the critical nature of complex microbial biofilms that form unique microbial ecologies and of their change during transition from health (homeostatic) to disease (dysbiotic). However, very little is known on how this alters their virulence and host responses. The objective of this study was to determine differences in virulence gene expression by pathobionts and the inflammatory host response in homeostatic and dysbiotic biofilms originating from the same ecology. Quantitative polymerase chain reaction was performed to quantify the pathobiont outgrowth. Expression analysis of bacterial virulence and cellular inflammatory genes together with cytokine enzyme-linked immunosorbent assays were used to detect differences in bacterial virulence and to analyze potential differences in inflammatory response. An increase in pathobionts in induced dysbiotic biofilms was observed compared to homeostatic biofilms. The main virulence genes of all pathobionts were upregulated in dysbiotic biofilms. Exposure of these dysbiotic biofilms to epithelial and fibroblast cultures increased the expression of interleukin (IL)-6, IL-1β, tumor necrosis factor-α, and matrix metalloprotease 8, but especially the chemokine CXCL8 (IL-8). Conversely, homeostatic and beneficial biofilms had a minor immune response at the messenger RNA and protein level. Overall, induced dysbiotic biofilms enriched in pathobionts and virulence factors significantly increased the inflammatory response compared to homeostatic and commensal biofilms.

Five-Year Survival of Short Single-Tooth Implants (6 mm): A Randomized Controlled Clinical Trial.

Abstract: The aim of the present study was to evaluate whether 6-mm dental implants in the posterior segments of either jaw perform equally well in terms of clinical and radiographic outcomes when compared with 10-mm implants after 5 y of loading. Patients with single-tooth gaps in the posterior area who were scheduled for implant therapy were randomly assigned to a group receiving either a 6- or 10-mm implant. After a healing period of 10 wk, implants were loaded with a screw-retained single crown and followed up at yearly intervals. Of 96 patients, 86 could be recalled after 5 y. The implant survival rates amounted to 91% (95% confidence interval: 0.836 to 0.998) for the 6-mm group and 100% for the 10-mm group ( P = 0.036). Median crown-to-implant (C/I) ratios were 1.75 (interquartile range [IQR], 1.50 to 1.90) for the 6-mm group and 1.04 (IQR, 0.95 to 1.15) for the 10-mm group, whereas the median marginal bone levels measured -0.29 mm (IQR, -0.92 to 0.23) for the 6-mm group and -0.15 mm (IQR: -0.93 - 0.41) for the 10-mm group after 5 y. The C/I ratio turned out to be statistically significant ( P < 0.001), whereas marginal bone levels showed no significant difference between the groups. The 6-mm implants exhibited significantly lower survival rates than the 10-mm implants over 5 y, whereas there was no difference between upper and lower jaws in terms of survival ( P = 0.58). Lost implants did not show any sign of marginal bone loss or peri-implant infection previous to loss of osseointegration. High C/I ratio and implant length had no significant effect on marginal bone level changes or technical and biological complications (German Clinical Trials Registry: DRKS00006290).

Emerging Insights into Wnt/β-catenin Signaling in Head and Neck Cancer:

Abstract: Head and neck cancer presents primarily as head and neck squamous cell carcinoma (HNSCC), a debilitating malignancy fraught with high morbidity, poor survival rates, and limited treatment options. Mounting evidence indicates that the Wnt/β-catenin signaling pathway plays important roles in the pathobiology of HNSCC. Wnt/β-catenin signaling affects multiple cellular processes that endow cancer cells with the ability to maintain and expand immature stem-like phenotypes, proliferate, extend survival, and acquire aggressive characteristics by adopting mesenchymal traits. A central component of canonical Wnt signaling is β-catenin, which balances its role as a structural component of E-cadherin junctions with its function as a transcriptional coactivator of numerous target genes. Recent genomic characterization of head and neck cancer revealed that while β-catenin is not frequently mutated in HNSCC, its activity is unchecked by more common mutations in genes encoding upstream regulators of β-catenin, NOTCH1, FAT1, and AJUBA. Wnt/β-catenin signaling affects a wide range epigenetic and transcriptional activities, mediated by the interaction of β-catenin with different transcription factors and transcriptional coactivators and corepressors. Furthermore, Wnt/β-catenin functions in a network with many signaling and metabolic pathways that modulate its activity. In addition to its effects on tumor epithelia, β-catenin activity regulates the tumor microenvironment by regulating extracellular matrix remodeling, fibrotic processes, and immune response. These multifunctional oncogenic effects of β-catenin make it an attractive bona fide target for HNSCC therapy.

Impact of HOTAIR Gene Polymorphism and Environmental Risk on Oral Cancer.

Abstract: Genetic and acquired factors are thought to be interrelated and imperative to estimate the risk and prognosis of oral squamous cell carcinoma (OSCC). HOX transcript antisense intergenic RNA (HOTAIR...