Dental composites continue to be the material of choice in daily dental practice for several reasons, including their good mechanical properties, conservative cavity design, and superior esthetics. However, the longevity of current resin composite restorations ranges only 5-10 years. Recurrent caries and tooth fracture are the most common types of failure during the first 6 years of clinical service. These failures are often caused by the polymerization shrinkage stress of the dental composite materials. Thus, there is an increased need to develop a new generation of bioactive dental composite with the ability to reduce polymerization shrinkage stress, long-term antibacterial, remineralization abilities, and excellent mechanical properties. Therefore, this dissertation aims to develop a new bioactive low-shrinkage-stress dental composite containing dimethylaminohexadecyl methacrylate (DMAHDM) and nanoparticles of amorphous calcium phosphate (NACP) which could be a promising approach to increase the chances of success of composite restorations and strengthen tooth structures. First, we found that the new bioactive low-shrinkage-stress resin composite significantly reduced the polymerization shrinkage stress, without compromising their mechanical properties. Increasing the DMAHDM mass fraction increased the antibacterial effect in a dose-dependent manner. Next, we investigated the low-shrinkage-stress composite mechanical stability and antibacterial durability in thermal cycling for 20,000 cycles, equivalent to two years of clinical life. We found that the bioactive low-shrinkage-stress composite possessed good mechanical properties that matched commercial composite both before and after thermal cycling. The new composite had potent antibacterial activity, which was maintained and did not decrease after thermal cycling. Lastly, we further examined the mechanical and antibacterial durability of a bioactive low-shrinkage-stress after 50,000 and 100,000 thermal cycles which corresponds to 5 and 10 years respectively of in vivo function. We found that the bioactive low-shrinkage-stress composite maintained its antibacterial potency after thermal cycling, indicating long-term antibacterial durability. In addition, it possessed good mechanical properties that were comparable to commercial composite both before and after thermal cycling. The triple benefits of antibacterial, remineralization, and lower shrinkage stress have a great potential to inhibit recurrent caries and increase restoration longevity.

Purpose: To assess the trueness of ceramic crowns fabricated using additive technology compared to crowns fabricated using subtractive technology. Material and methods: single crown was designed using Dental Designer Software. 3D design was used to fabricate milled and printed crowns. All crowns were scanned. Geomagic software was used for analysis. Best Fit and Marginal Fit Alignment used to analyze the 3D accuracy of the crowns. One Way ANOVA used to analyze the data, and p<0.05 was considered significant. Result: Significant differences found between the additively and subtractive manufactured crowns [p=0.003,F=11.172]. Additively manufactured crowns exhibited better trueness than subtractive crowns. For the additively manufactured crowns, the Best fit Alignment showed 42.81±40.8μm deviation, and the Marginal Alignment showed a 43.11 ±38.05μm deviation. For Subtractive manufactured crowns, the deviation in Best Fit Alignment was 62.67 ±50.79μm and in Marginal Alignment was 55.35±48.69μm. Conclusion: Additive technology fulfills surface trueness criteria.

Purpose: To assess and compare caries experience based on an epidemiological “screening” examination and a routine examination with radiographs. Methods: 128 patients ages 5 to 10 years were included. An initial examination was done by a pediatric dentist in conditions simulating an epidemiological screening assessment. A second evaluation was done by eight postgraduate pediatric dental resident who conducted a routine clinical exam of the patient in the dental chair including radiographs. Results: By the epidemiological screening, the prevalence of untreated dental caries (Y/N) in primary and/or permanent teeth was 50% and the caries experience was 77%. After the routine examination with radiographs, the prevalence of untreated dental caries was 74.22% and caries experience was 90%. The severity of untreated dental caries was 2.0 and 3.9, and the severity of caries experience was 3.2 and 5.6 by the simulated epidemiological screening and routine examination with radiographs, respectively.

Dysregulation of cellular signaling is instrumental in the promotion of tumor cell metabolism, proliferation, tissue invasion and metastasis. Molecular-based therapies for neoplastic diseases are designed to modulate or interact with cell surface receptors, intracellular cascades, or microenvironment components related to the extracellular matrix, tumor vasculature and immune response. To design these therapies, an improved understanding of the molecular underpinnings leading to tumor growth is essential. The overall aim of our investigation is identification of the molecular mechanisms associated with the induction of tumor cell migration and proliferation induced by Angiopoietin-like 4 (ANGPTL4), a pro-tumorigenic and pro-angiogenic factor, in head and neck cancer squamous cell carcinoma (HNSCC). HNSCC accounts for around 54,000 new cases and 11,000 deaths per year in the United States. Unfortunately, the clinical management of this tumor remains challenging. Our studies, divided into two research aims, use in vitro cell-based models together with signal transduction and cell and molecular biology methods. Our results demonstrate that: 1) ANGPTL4 is upregulated in human-derived dysplastic oral keratinocytes (DOKs) and HNSCC cell lines, but not in normal oral keratinocytes (NOKs), suggesting an early and sustained role for ANGPTL4 in disease progression. ANGPTL4 is a molecular marker in biopsies from patients with mild-moderate or moderate oral epithelial dysplasia, primary HNSCC and metastatic HNSCC. ANGPTL4 is necessary and sufficient to promote cell migration in DOKs and HNSCCs lines. Binding of ANGPTL4 to neuropilin-1 (NRP1) leads to paxillin (PXN) phosphorylation and cell migration in an ABL1-dependent manner, exposing the ANGPTL4/NRP1/ABL1/PXN cascade as a vulnerable target for HNSCC treatment. 2) Epidermal Growth Factor (EGF)- and Hypoxia-inducible Factor-1 (HIF-1)-mediated pathways cooperate in the upregulation of ANGPTL4 in normal and dysplastic oral keratinocytes and HNSCC cells. Besides EGF, the EGF ligand amphiregulin leads to an increase in ANGPTL4 and is upregulated in HNSCC lesions. ANGPTL4 activates the HNSCC molecular markers p38 MAPK, AKT and mTOR in NOKs; these kinases may act as potential intracellular regulators of the autocrine signals and paracrine secretions that ANGPTL4 activates to promote HNSCC tumorigenesis. Collectively, our findings suggest that ANGPTL4 and its associated signaling molecules are potential therapeutic targets in HNSCC clinical management.

Objective: To determine an optimal antero-posterior (AP) position of the maxillary central incisors (CI) and its relationship to the forehead in African American males. Methods: 95 smiling profile photographs were taken, evaluated by orthodontists and laypersons, and categorized in Group B, R or F. The CI position and forehead inclination (FI) were measured relative to glabella vertical (GV). Statistical analysis evaluated the relationship between CI position and FI, differences between groups, and differences between orthodontists and laypersons. Results: Optimal CI position was -2.1mm behind GV. There were no significant differences between orthodontists and laypersons. All group comparisons were significantly different, except Group B v Group R. The optimal CI position relative to GV and FI were not significantly correlated. Conclusions: The AP position of the CI relative to the forehead in African American males can be evaluated to determine the optimal AP position of the CI and optimal esthetics.

Purpose: An in vivo study to compare microtensile bond strength and resin tag density of a novel adhesive that relies on magnetic force. Materials and Methods: Twenty-five teeth were obtained from subjects. In the experimental group, teeth were restored with a novel nanoparticle adhesive and magnetic force (n=16). In the control group (n=9), no nanoparticle or magnetic force was used. Teeth were extracted and cut into beams. Microtensile bond strength and resin tag density were measured. A two tailed student t test was used to compare groups. P<0.05 was considered significant. Results: There was a significant increase of microtensile bond strength of the experimental group compared to controls (P= 0.025). The SEM images showed resin tag density was increased by a magnitude of two with the experimental group. Conclusion: Magnetic force improves the microtensile bond strength and resin tag density of resin adhesive when used in vivo.

This laboratory-based study investigated the accuracy of transferring the VDO of the maxillary/mandibular relationship when designing and fabricating digital dentures by evaluating two commonly used workflows: duplicate dentures (DD) and occlusion rims (OR). 15 STLs were obtained for each workflow. Three measurements in deviation (mm) were obtained, then 3D-deviation values were averaged for each workflow at each location. A two-way ANOVA was used for the statistical analysis to evaluate differences between the methods and location of measurement. The average deviation for OR was higher than DD at all locations of measurement. There was a statistically significant difference between the DD and OR workflows [F=46.00, p<0.0001]. There was no statistically significant difference in deviation between the points of measurement [F=0.15, p<0.86] or between the location and method [F=0.02, p<0.98]. The DD workflow exhibited less deviation in transfer of VDO than the OR workflow. The location of the measurements had no significance.

The objectives of this dissertation were to: (1) investigate a bioactive nanocomposite with strong antibacterial and ion-recharge capabilities containing dimethylaminododecyl methacrylate (DMAHDM) and nanoparticles of amorphous calcium phosphate (NACP), and evaluate long-term Ca and P ion recharge by testing for 12 cycles of recharge and release; (2) develop a low-shrinkage-stress (LSS) nanocomposite with antibacterial and remineralization capabilities through the incorporation of DMAHDM and NACP to reduce marginal enamel and dentin demineralization under recurrent caries biofilm-model; (3) investigate the effects of the new composite on biofilm inhibition, mechanical properties, shrinkage stress, degree of conversion, and Ca and P ion releases; and (4) investigate the cytotoxicity of the new LSS composite and its monomers in vitro. For the antibacterial and rechargeable nanocomposite, biofilm lactic acid and colony-forming units (CFU) were measured. Ion recharge was tested for 12 cycles. For the LSS antibacterial and remineralizing nanocomposite, mechanical properties, shrinkage stress, and degree of conversion were evaluated. The growth of Streptococcus mutans and multi-species salivary biofilms was assessed using biofilm CFU, lactic acid production, and confocal laser scanning microscopy. Ca and P ion releases, and human gingival fibroblasts cytotoxicity were measured. The bioactive rechargeable nanocomposite reduced biofilm acid production and viability. High levels of ion releases were maintained throughout 12 cycles of recharge, maintaining steady-state releases without reduction in 6 months, representing long-term remineralization potential. The LSS composite with DMAHDM and NACP had flexural strength matching that of a commercial control composite. The bioactive low-shrinkage-stress composite substantially reduced the biofilm CFU and lactic acid production compared to control composite. The bioactive LSS composite exhibited no significant difference in antibacterial performance before and after three months of aging, demonstrating long-term antibacterial activity. The shrinkage stress of the bioactive low-shrinkage-stress nanocomposite was 36% lower than that of traditional control composite, with similar degrees of conversion. The new bioactive nanocomposite had a satisfactorily low cytotoxic effect toward human gingival fibroblasts and the new monomers had fibroblast viability similar to that of commercial control. The two developed nanocomposites are promising to inhibit recurrent caries and protect the teeth with an intended application for reducing recurrent caries.

It is desirable to use a minimally invasive approach in dentistry through conservative techniques in order to prevent destruction of the tooth structure. Since resin-based dental materials are increasingly used, the occurrence of re-infections is also increasing. Recurrent caries and secondary infections are major problems in the restorative dentistry field. The prevalence of recurrent caries associated with resin-based restorative materials was previously shown to reach 60%. It is the most common reason recognized for composite resin restorations replacement and failure. Many efforts have been made to incorporate antibacterial agents into restorative materials. However, the majority of these materials act by releasing these agents into the surrounding environment, leading to their depletion over time. There is a clinical need for durable bioactive composite restorations that resist the formation of secondary caries for an extended period of time. Dimethylaminohexadecyl methacrylate (DMAHDM) is an antibacterial agent that is immobilized in resin and not lost or released with time. Therefore, this dissertation aims to develop new composite resin formulations containing DMAHDM antibacterial, 2-methacryloyloxyethyl phosphorylcholine (MPC) protein repellent, and nanoparticles of calcium fluoride (nCaF2) remineralizing modalities which could be a promising approach for management of recurrent caries around or under restoration margins. This dissertation incorporated DMAHDM, MPC and nCaF2 into composite resin restorations to achieve potent, long-lasting antibacterial, protein repellent, and Ca and F ion release and recharge/re-release capabilities. Mechanical testing was performed for all composite formulations. To determine biofilm properties, a human salivary microcosm biofilm model was used. Biofilm colony-forming units (CFU), minimum inhibitory concentration, lactic acid production, and metabolic activity of biofilm were investigated. Fluoride (F) and calcium (Ca) initial ion releasing, recharging and re-releasing capabilities were tested. The majority of nCaF2 nanocomposites show matching mechanical properties to the commercial control composite. The nCaF2-DMAHDM nanocomposites have potent antibacterial effects that substantially reduce biofilm activities in all biofilm experiments. Similarly, all nCaF2 nanocomposites have higher values of F and Ca ion release- recharge, and re-release when compared to the commercial control composite. Therefore, these new composite resin formulations may potentially lead to a fundamental contribution in restorative techniques that can be used to fight this most common limitation of composite restorations - recurrent caries - and contribute to the longevity of composite restorations through long-lasting antibacterial and protein repellent properties and remineralization capabilities.

In the United States, nearly 1 million people suffer from burning mouth syndrome (BMS), a chronic orofacial pain condition that is largely unrecognized by the medical community and predominantly affects post- and peri-menopausal women. Relatively little in-depth research is available on the condition, and patients often give up seeking treatment. The pain in BMS arises spontaneously (i.e. in the absence of stimuli), but the mechanisms of this spontaneous pain is unclear, and there is limited research on structural and functional brain changes that may occur in a BMS sufferer. The goal of this dissertation was to investigate the central nervous system mechanisms of pain experienced in BMS. We collected: 8-day diaries, morning and afternoon quantitative sensory testing of both orofacial and forearm regions; afternoon structural and functional MRIs, and questionnaires from 27 BMS patients and 33 healthy post-menopausal women. Our hypotheses that, compared to healthy participants BMS patients have: higher pain sensitivity, especially in orofacial regions during the afternoon; lower grey matter volume and higher functional connectivity in nociceptive pathways associated with noxious heat during rest and evoked thermal pain, even after accounting for anxiety, were not supported. Instead, we found a time-of-day-dependent effect during warm detection and cold detection of face and forearm; lower grey matter volume of the dorsolateral prefrontal cortex (DLPFC), and higher grey matter volume of the inferior temporal gyrus and parabrachial nucleus (PBN); lower PBN connectivity with the DLPFC and primary somatosensory cortex (S1); higher connectivity of the right lateral hypothalamus (LH) with posterior insula during warm condition; connectivity of right medial hypothalamus and LH to left DLPFC and right PBN to bilateral S1 not associated with anxiety in BMS compared to healthy participants. Altogether, BMS showed abnormal responses to innocuous stimuli. This was supported by fMRI data, where connectivity differences were mostly present during innocuous stimulation. These altered sensory and brain responses could reflect heightened anticipation of thermal stimuli (both pain-specific and non-pain specific) associated with disruption of communication between regions associated with negative affect of pain (insula), attention modulation of pain (left DLPFC), somatosensation (S1), and thermoregulation (LH and PBN).