Dentistry: Getting Beyond Earth’s Orbit
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Christopher T Haas↗
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Advanced characterization of surface-modified nanoparticles and nanofilled antibacterial dental adhesive resins
Nanotechnology can improve the performance of dental polymers. The objective of this study was to modify the surfaces of nanoparticles with silanes and proteins, characterize nanoparticles’ agglomeration levels and interfaces between nanoparticles and the polymeric matrix. Undoped (n-TiO 2 ), nitrogen-doped (N_TiO 2 ) and nitrogen-fluorine co-doped titanium dioxide nanoparticles (NF_TiO 2 ) were synthesized and subjected to surface modification procedures in preparation for Small-Angle X-Ray Scattering (SAXS) and Small-Angle Neutron Scattering (SANS) characterizations. Experimental adhesives were manually synthesized by incorporating 20% (v/v) of n-TiO 2 , N_TiO 2 or NF_TiO 2 (as-synthesized or surface-modified) into OptiBond Solo Plus (OPTB). Specimens (n = 15/group; d = 6.0 mm, t = 0.5 mm) of OPTB and experimental adhesives were characterized using Time-of-Flight Secondary Ion Mass Spectroscopy (ToF-SIMS), 2-D ToF-SIMS chemical imaging and SANS. SAXS results indicated that surface-modified nanoparticles displayed higher scattering intensities in a particle-size dependent manner. ToF-SIMS results demonstrated that nanoparticles’ incorporation did not adversely impact the parental polymer. 2-D ToF-SIMS chemical imaging demonstrated the distribution of Ti + and confirmed nitrogen-doping levels. SANS results confirmed nanoparticles’ functionalization and revealed the interfaces between nanoparticles and the polymer matrix. Metaloxide nanoparticles were successfully fabricated, incorporated and covalently functionalized in a commercial dental adhesive resin, thereby supporting the utilization of nanotechnology in dentistry.
60 APPLIED LIFE SCIENCES↗
Mesoscale structural gradients in human tooth enamel
The outstanding mechanical and chemical properties of dental enamel emerge from its complex hierarchical architecture. An accurate, detailed multiscale model of the structure and composition of enamel is important for understanding lesion formation in tooth decay (dental caries), enamel development (amelogenesis) and associated pathologies (e.g., amelogenesis imperfecta or molar hypomineralization), and minimally invasive dentistry. Although features at length scales smaller than 100 nm (individual crystallites) and greater than 50 µm (multiple rods) are well understood, competing field of view and sampling considerations have hindered exploration of mesoscale features, i.e., at the level of single enamel rods and the interrod enamel (1 to 10 µm). Here, we combine synchrotron X-ray diffraction at submicrometer resolution, analysis of crystallite orientation distribution, and unsupervised machine learning to show that crystallographic parameters differ between rod head and rod tail/interrod enamel. This variation strongly suggests that crystallites in different microarchitectural domains also differ in their composition. Thus, we use a dilute linear model to predict the concentrations of minority ions in hydroxylapatite (Mg 2+ and CO 3 2- /Na + ) that plausibly explain the observed lattice parameter variations. While differences within samples are highly significant and of similar magnitude, absolute values and the sign of the effect for some crystallographic parameters show interindividual variation that warrants further investigation. In conclusion, by revealing additional complexity at the rod/interrod level of human enamel and leaving open the possibility of modulation across larger length scales, these results inform future investigations into mechanisms governing amelogenesis and introduce another feature to consider when modeling the mechanical and chemical performance of enamel.
71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗
TiO 2 Nanocoatings with Controllable Crystal Type and Nanoscale Topography on Zirconia Implants to Accelerate Bone Formation
In dentistry, zirconia implants have emerged as a promising alternative for replacing missing teeth due to their superior aesthetic performance and chemical stability. To improve the osseointegration of zirconia implants, modifying their surface with hierarchical micro/nanotopography and bioactive chemical composition are two effective ways. In this work, a microscale topography was prepared on a zirconia surface using hydrofluoric acid etching, and then a 50 nm TiO 2 nanocoating was deposited via atomic layer deposition (ALD). Subsequently, an annealing treatment was used to transform the TiO 2 from amorphous to anatase and simultaneously generate nanoscale topography. Various investigations into the coating surface morphology, topography, wettability, and chemical composition were carried out using scanning electron microscopy, white light interferometry, contact‐angle measurement, X‐ray diffraction, and X‐ray photoelectron spectroscopy. In addition, in vitro cytocompatibility and osteogenic potential performance of the coatings were evaluated by human bone marrow mesenchymal stem cells (hBMSCs), and in vivo osseointegration performance was assessed in a rat femoral condyle model. Moreover, the possible mechanism was also investigated. The deposition of TiO 2 film with/without annealing treatment did not alter the microscale roughness of the zirconia surface, whereas the nanotopography changed significantly after annealing. The in vitro studies revealed that the anatase TiO 2 coating with regular wavelike nanostructure could promote the adhesion and proliferation of osteoblasts and further improve the osteogenic potential in vitro and osseointegration in vivo. These positive effects may be caused by nanoscale topography via the canonical Wnt/ β ‐catenin pathway. The results suggest that using ALD in combination with annealing treatment to fabricate a nanotopographic TiO 2 coating is a promising way to improve the osteogenic properties of zirconia implants.
Li, Nan (ORCID:0000000255156737)↗
Chemico-therapeutic approach to prevention of dental caries
The program of chemical preventive dentistry is based primarily upon the development of a procedure for stabilizing stannous fluoride in solution by forcing it into glycerin. New topical fluoride treatment concentrates, fluoride containing gels and prophylaxis pastes, as well as a completely stable stannous fluoride dentifrice are made possible by the development of a rather complicated heat application method to force stannous fluoride into solution in glycerin. That the stannous fluoride is clinically effective in such a preparation is demonstrated briefly on orthodontic patients.
Shannon, I. L.↗
Skylab oral health studies
Oral health considerations for the Skylab series of manned space flights included three general areas of responsibility. These areas were: Clinical dentistry; Provisions for the in-flight care and the in-flight medical support system-dental; Research dedicated to the identification of potential oral problems manned space missions of long duration.
Lee R. Brown↗
Dental research: Preliminary observations and projections
The potential applicability of the Lixiscope in dentistry was investigated. Conceptual limitations on basic design requirements common to the Lixiscope are discussed.
Webber, R. L.↗
Maxillo: Facial diagnosis
The application of the Lixiscope in dentistry was studied. Due to a problem in resolution, it is concluded that, at this present time, the Lixiscope can only be as a previewing device for conventional radiography.
Reiskin, A. B.↗
NASA: Biomedical applications team
The status of projects involving the adaptation of NASA technologies for medical purposes is reviewed. Devices for the measurement of joint deformation of arthritic hands, the development of an artificial pancreas, provision of an auditory signal to avert epileptic seizures, are described along with the control of medication levels, a compressed air tank to supply power for field dentistry, and an electroencephalogram monitor. The use of the Lixiscope as a portable fluoroscope, thermal laminates for hand and foot warmers for patients with Raynaud's syndrome, and the use of absorptive coatings for instruments for controlling medication levels are described. The applicability of occupation health and safety practices to industry, computerized patient scheduling, impregnation of the common facial tissue with an agent for killing respiratory viruses, commercial applications of anthropometric data, and multispectral image analysis of the skin as a diagnostic tool are reviewed.
Source record↗
Molding Compound For Inspection Of Internal Contours
Material clean, sets rapidly, and easy to use. Silicone elastomer, Citrocon or equivalent, commonly used in dentistry, in combination with mold-release agent (Also see MFS-29240), speeds and facilitates making of impressions of interior surfaces so surface contours examined. Elastomer easily moved around in cavity until required location found.
Adams, Jim↗
Adjustable-Viewing-Angle Endoscopic Tool for Skull Base and Brain Surgery
The term Multi-Angle and Rear Viewing Endoscopic tooL (MARVEL) denotes an auxiliary endoscope, now undergoing development, that a surgeon would use in conjunction with a conventional endoscope to obtain additional perspective. The role of the MARVEL in endoscopic brain surgery would be similar to the role of a mouth mirror in dentistry. Such a tool is potentially useful for in-situ planetary geology applications for the close-up imaging of unexposed rock surfaces in cracks or those not in the direct line of sight. A conventional endoscope provides mostly a frontal view that is, a view along its longitudinal axis and, hence, along a straight line extending from an opening through which it is inserted. The MARVEL could be inserted through the same opening as that of the conventional endoscope, but could be adjusted to provide a view from almost any desired angle. The MARVEL camera image would be displayed, on the same monitor as that of the conventional endoscopic image, as an inset within the conventional endoscopic image. For example, while viewing a tumor from the front in the conventional endoscopic image, the surgeon could simultaneously view the tumor from the side or the rear in the MARVEL image, and could thereby gain additional visual cues that would aid in precise three-dimensional positioning of surgical tools to excise the tumor. Indeed, a side or rear view through the MARVEL could be essential in a case in which the object of surgical interest was not visible from the front. The conceptual design of the MARVEL exploits the surgeon s familiarity with endoscopic surgical tools. The MARVEL would include a miniature electronic camera and miniature radio transmitter mounted on the tip of a surgical tool derived from an endo-scissor (see figure). The inclusion of the radio transmitter would eliminate the need for wires, which could interfere with manipulation of this and other surgical tools. The handgrip of the tool would be connected to a linkage similar to that of an endo-scissor, but the linkage would be configured to enable adjustment of the camera angle instead of actuation of a scissor blade. It is envisioned that thicknesses of the tool shaft and the camera would be less than 4 mm, so that the camera-tipped tool could be swiftly inserted and withdrawn through a dime-size opening. Electronic cameras having dimensions of the order of millimeters are already commercially available, but their designs are not optimized for use in endoscopic brain surgery. The variety of potential endoscopic, thoracoscopic, and laparoscopic applications can be expected to increase as further development of electronic cameras yields further miniaturization and improvements in imaging performance.
Bae, Youngsam↗
Novel Amalgams for In-Space Fabrication of Replacement Parts
Being able to fabricate replacement parts during extended space flight missions precludes the weight, storage volume, and speculation necessary to accommodate spares. Amalgams, widely used in dentistry, are potential candidates for fabricating parts in microgravity environments as they are moldable, do not require energy for melting, and do not pose fluid handling problems. Unfortunately, amalgams have poor tensile strength and the room temperature liquid component is mercury. To possibly resolve these issues a gallium-indium alloy was substituted for mercury and small steel fibers were mixed in with the commercial alloy powder. Subsequent microscopic examination of the novel amalgam revealed complete bonding of the components, and mechanical testing of comparable samples showed those containing steel fibers to have a significant improvement in strength. Experimental procedures, microstructures, and test results are presented and discussed in view of further improving properties.
Cochran, Calvin T.↗
Enhanced Tooth Structure Via Silver Microwires Following Treatment with 38 Percent Silver Diamine Fluoride.
The American Academy of Pediatric Dentistry guidelines recommend treatment of primary teeth with 38 percent silver diamine fluoride (SDF) as a noninvasive option to arrest active dental caries lesions. A significant outcome of SDF treatment are lesions that clinically harden and become more resistant to further decay. Many practicing dentists believe that this increased hardening is due to the reaction of silver and fluoride with carious dentin. The purpose of this study was to focus on the structural and chemical effects of silver diamine fluoride treatment on the native tooth. In SDF-treated cavitated dentin lesions in teeth subsequently extracted for orthodontic reasons, the authors observed continuous, filamentous silver densities formed in situ from 50 to 2,100 μm in length and 0.25 to 7.0 μm in diameter using high-resolution synchrotron X-ray microcomputer tomography and field emission scanning electron microscopy. These "microwires" fill voids in the lesion caused by disease and permeate through surrounding dentinal tubules. Spectroscopy confirmed that the chemical composition of the observed microwires is predominantly silver. These observations suggest mechanistic explanations for the structural reinforcement of carious dentin in addition to remineralization. It is hypothesized that silver diamine fluoride may achieve its antimicrobial functions by biochemical interactions and through its inherent ability to integrate into the native tooth structure.
60 APPLIED LIFE SCIENCES↗
Enhanced Tooth Structure Via Silver Microwires Following Treatment with 38 Percent Silver Diamine Fluoride.
Purpose: American Academy of Pediatric Dentistry guidelines recommend treatment of primary teeth with 38 percent silver diamine fluoride (SDF) as a noninvasive option to arrest active dental caries lesions. A significant outcome of SDF treatment are lesions that clinically harden and become more resistant to further decay. Many practicing dentists believe that this increased hardening is due to the reaction of silver and fluoride with carious dentin. The purpose of this study was to focus on the structural and chemical effects of silver diamine fluoride treatment on the native tooth. Methods: In SDF-treated cavitated dentin lesions in teeth subsequently extracted for orthodontic reasons, the authors observed continuous, filamentous silver densities formed in situ from 50 to 2,100 μm in length and 0.25 to 7.0 μm in diameter using high-resolution synchrotron X-ray microcomputer tomography and field emission scanning electron microscopy. These microwires fill voids in the lesion caused by disease and permeate through surrounding dentinal tubules. Results: Spectroscopy confirmed that the chemical composition of the observed microwires is predominantly silver. Conclusions: These observations suggest mechanistic explanations for the structural reinforcement of carious dentin in addition to remineralization. It is hypothesized that silver diamine fluoride may achieve its antimicrobial functions by biochemical interactions and through its inherent ability to integrate into the native tooth structure.
60 APPLIED LIFE SCIENCES↗
Nanoparticle-mediated antagonism of sustained endosomal signaling of the calcitonin receptor-like receptor provides enhanced and persistent relief of oral cancer pain
By improving the delivery and tumor retention of chemotherapeutics, nanomedicines hold potential for cancer treatment. The usefulness of nanoparticle (NP)-encapsulated analgesics for the cancer pain treatment is comparatively unexplored. We investigated whether NPs encapsulating olcegepant (OCP), an antagonist of the calcitonin receptor-like receptor (CLR) for the calcitonin gene-related peptide (CGRP), effectively relieved oral cancer pain in mice. Because persistent endosomal CLR signaling in Schwann cells mediates craniofacial pain, we reasoned that the predisposition of NPs to accumulate in endosomes could be leveraged to effectively relieve oral cancer pain. By expressing biosensors for activated CLR, Gα proteins and β-arrestins in HEK293T and Schwann cells, we found that CGRP activates CLR signaling first at the plasma membrane and then in early, late and recycling endosomes and the cis- and trans-Golgi apparatus. We synthesized biocompatible NPs encapsulating OCP and fluorophores by integrating hydrophobic ion pairing nanoformulation with Flash NanoPrecipitation. NPs slowly released OCP and accumulated in early endosomes, leading to sustained inhibition of endosomal CLR signaling in HEK293T and Schwann cells. Oral cancers were established in mice, which led to heightened pain-like responses. After intra-tumoral injection, NPs were retained in tumors for at least one week. OCP-loaded NPs almost completely reversed allodynia and hyperalgesia for a prolonged period, whereas unencapsulated OCP had small and transient effects. The NP accumulation in endosomal sites of pain signaling, the sustained release of antagonist, and the retention of NPs in tumors explain their beneficial actions. Thus, NP-encapsulation holds promise for the relief of painful cancers that are inadequately treated by opioids.
Calcitonin gene-related peptide↗
A Machine Learning Approach to Quantitative Analysis of Enamel Microstructure from Scanning Electron Microscopy Images
Dental enamel, the outermost tissue of mammalian teeth, must withstand a lifetime of wear and cyclic contact. To meet this demand, enamel possesses a combination of high hardness and resistance to fracture, properties that are typically mutually exclusive. The impressive damage tolerance has been attributed largely to decussation of the enamel rods, the principal unit of its microstructure. As such, enamel is inspiring the design of next‐generation structural materials. However, quantitative descriptions of the decussated enamel rod microstructure remain limited due to challenges encountered in applying computed tomography and in acquiring quality images appropriate for traditional digital processing methods. Here, a machine learning segmentation method is applied to images of the enamel obtained using scanning electron microscopy to support quantitative analysis of the microstructure. A pretrained convolutional neural network is used to expand the input training image dataset to allow the training of a random forest classifier, which ultimately segments the image with a very small training set ( n = 3 images). A validation of this segmentation method is presented, in addition to its application to calculate relevant microstructural parameters for images of tooth enamel from selected mammalian species. The methodology applied here is equally applicable to other hard tissues.
36 MATERIALS SCIENCE↗
Small-molecule modulation of β-arrestins
β-Arrestins are multifunctional regulators of G-protein-coupled receptor (GPCR) signalling and orchestrate diverse downstream signalling events and physiological responses across the GPCR superfamily. Although GPCR pharmacology has advanced to target orthosteric and allosteric sites, as well as G proteins and GPCR kinases, direct chemical tools to modulate β-arrestin activities have remained conspicuously absent. Here we report the identification of small-molecule inhibitors that selectively target β-arrestins and delineate their mechanism of action through integrated pharmacological, biochemical, biophysical and structural analyses. These inhibitors disrupt β-arrestin engagement with agonist-activated GPCRs, impairing desensitization, internalization and β-arrestin-dependent physiological functions while sparing G protein–receptor coupling. Cryo-electron microscopy, molecular dynamics simulations and structure-guided mutagenesis reveal that one modulator, Cmpd-5, engages a pocket within the central crest of β-arrestin1 formed by the middle, C and lariat loops, a critical receptor-binding interface, stabilizing a distinct conformation that is incompatible with full β-arrestin–receptor engagement. Together, these findings establish a mechanistic framework for β-arrestin modulation, reveal a novel allosteric site for structure-based drug design, and open new avenues for transducer-targeted, pathway-specific GPCR therapeutic agents.
Kahsai, Alem W. [Duke University, Durham, NC (Unit↗
Sorted-cell proteomics reveals an AT1-associated epithelial cornification phenotype and suggests endothelial redox imbalance in human bronchopulmonary dysplasia
Bronchopulmonary dysplasia (BPD) is a neonatal lung disease characterized by inflammation and scarring leading to long-term tissue damage. Previous whole tissue proteomics identified BPD-specific proteome changes and cell type shifts. Little is known about the proteome-level changes within specific cell populations in disease. Here, we sorted epithelial (EPI) and endothelial (ENDO) cell populations based on their differential surface markers from normal and BPD human lungs. Using a low-input compatible sample preparation method (MicroPOT), proteins were extracted and digested into peptides and subjected to liquid chromatography-tandem mass spectrometry (LC-MS/MS) proteome analysis. Of the 4,970 proteins detected, 293 were modulated in abundance or detection in the EPI population and 422 were modulated in ENDO cells. Modulation of proteins associated with actin-cytoskeletal function, such as SCEL, LMO7, and TBA1B was observed in the BPD EPIs. Using confocal imaging and analysis, we validated the presence of aberrant multilayer-like structures comprising SCEL and LMO7, known to be associated with epidermal cornification, in the human BPD lung. This is the first report of the accumulation of cornification-associated proteins in BPD. Their localization in the alveolar parenchyma, primarily associated with alveolar type 1 (AT1) cells, suggests a role in the BPD postinjury response. In the ENDOs, redox balance and mitochondrial function pathways were modulated. Alternative mRNA splicing and cell proliferative functions were elevated in both populations, suggesting potential dysregulation of cell progenitor fate. This study characterized the proteome of epithelial and endothelial cells from the BPD lung for the first time, identifying population-specific changes in BPD pathogenesis.
BPD↗