Elevated activity levels do not influence extrinsic fiber attachment morphology on the surface of muscle-attachment sites.

Extrinsic fibers (EFs) are a type of penetrating collagenous fiber, closely related to the periodontal ligament, which help anchor soft tissue into bone. These fibers are associated with muscle attachment sites (entheses). Their size and grouping patterns are thought to be indicative of the loading history of the muscle. EFs are of particular significance in anthropology as potential tools for the reconstruction of behavior from skeletal remains and, specifically, entheses. In this study, we used a mouse model to experimentally test how activity level alters the morphology of EF insertion sites on the bone surface of a fibrocartilaginous enthesis, the biceps brachii insertion. Further, we adapted surface metrological techniques from studies of dental wear to perform automated, quantitative and non-destructive analysis of bone surface histology. Our results show that experimentally increased activity had no significant effect on the quantity or density of EF insertions at the enthesis, nor on the size of those insertions. Although EF presence does indicate muscle attachment, activity did not have an observable effect on EF morphology.

Meticulous Doxorubicin Release from pH-Responsive Nanoparticles Entrapped within an Injectable Thermoresponsive Depot.

The dual stimuli-controlled release of doxorubicin from gel-embedded nanoparticles is reported. Non-cytotoxic polymer nanoparticles are formed from poly(ethylene glycol)-b-poly(benzyl glutamate) that, uniquely, contain a central ester link. This connection renders the nanoparticles pH-responsive, enabling extensive doxorubicin release in acidic solutions (pH 6.5), but not in solutions of physiological pH (pH 7.4). Doxorubicin-loaded nanoparticles were found to be stable for at least 31 days and lethal against the three breast cancer cell lines tested. Furthermore, doxorubicin-loaded nanoparticles could be incorporated within a thermoresponsive poly(2-hydroxypropyl methacrylate) gel depot, which forms immediately upon injection of poly(2-hydroxypropyl methacrylate) in dimethyl sulfoxide solution into aqueous solution. The combination of the poly(2-hydroxypropyl methacrylate) gel and poly(ethylene glycol)-b-poly(benzyl glutamate) nanoparticles yields an injectable doxorubicin delivery system that facilities near-complete drug release when maintained at elevated temperatures (37 °C) in acidic solution (pH 6.5). In contrast, negligible payload release occurs when the material is stored at room temperature in non-acidic solution (pH 7.4). The system has great potential as a vehicle for the prolonged, site-specific release of chemotherapeutics.

Effective Differentiation of Induced Pluripotent Stem Cells Into Dental Cells.

BACKGROUND: A biotooth is defined as a complete living tooth, made in laboratory cultures from a spontaneous interplay between epithelial and mesenchymal cell-based frontal systems. A good solution to these problems is to use induced pluripotent stem cells (iPSCs). However, no one has yet formulated culture conditions that effectively differentiate iPSCs into dental epithelial and dental mesenchymal cells phenotypes analogous to those present in tooth development. RESULTS: Here, we tried to induce differentiation methods for dental epithelial cells (DEC) and dental mesenchymal cells from iPSCs. For the DEC differentiation, the conditional media of SF2 DEC was adjusted to embryoid body. Moreover, we now report on a new cultivation protocol, supported by transwell membrane cell culture that make it possible to differentiate iPSCs into dental epithelial and mesenchymal cells with abilities to initiate the first stages in de novo tooth formation. CONCLUSIONS: Implementation of technical modifications to the protocol that maximize the number and rate of iPSC differentiation, into mesenchymal and epithelial cell layers, will be the next step toward growing an anatomically accurate biomimetic tooth organ. Developmental Dynamics 248:129-139, 2019. © 2018 Wiley Periodicals, Inc.

Cell cycle of the enamel knot during tooth morphogenesis.

Enamel knot (EK) is known to be a central organ in tooth development, especially for cusp patterning. To trace the exact position and movement among the inner dental epithelium (IDE) and EK cells, and to monitor the relationship between the EK and cusp patterning, it is essential that we understand the cell cycle status of the EK in early stages of tooth development. In this study, thymidine analogous (IdU, BrdU) staining was used to evaluate the cell cycle phase of the primary EK at the early casp stage (E13.0) and the gerbil embryo (E19) in a developing mouse embryo. The centerpiece of this study was to describe the cell cycle phasing and sequencing during proliferation in the IDE according to the expression of IdU and BrdU following their injection at calculated time points. The interval time between IdU injection and BrdU injection was set at 4 h. As a result, the cell cycle in the IDE of the mouse and gerbil was found to be synchronous. Conversely, the cell cycle in primary EKs of mice was much longer than that of the IDE. Therefore, the difference of cell cycle of the IDE and the EK is related to the diversity of cusp patterning and would provide a new insight into tooth morphogenesis.

The upper limb of Homo naledi.

The evolutionary transition from an ape-like to human-like upper extremity occurred in the context of a behavioral shift from an upper limb predominantly involved in locomotion to one adapted for manipulation. Selection for overarm throwing and endurance running is thought to have further shaped modern human shoulder girdle morphology and its position about the thorax. Homo naledi (Dinaledi Chamber, Rising Star Cave, Cradle of Humankind, South Africa) combines an australopith-like cranial capacity with dental characteristics akin to early Homo. Although the hand, foot, and lower limb display many derived morphologies, the upper limb retains many primitive traits. Here, we describe the H. naledi upper extremity (excluding the hand) in detail and in a comparative context to evaluate the diversity of clavicular, scapular, humeral, radial, and ulnar morphology among early hominins and later Homo. Homo naledi had a scapula with a markedly cranially-oriented glenoid, a humerus with extremely low torsion, and an australopith-like clavicle. These traits indicate that the H. naledi scapula was situated superiorly and laterally on the thorax. This shoulder girdle configuration is more similar to that of Australopithecus and distinct from that of modern humans, whose scapulae are positioned low and dorsally about the thorax. Although early Homo erectus maintains many primitive clavicular and humeral features, its derived scapular morphology suggests a loss of climbing adaptations. In contrast, the H. naledi upper limb is markedly primitive, retaining morphology conducive to climbing while lacking many of the derived features related to effective throwing or running purported to characterize other members of early Homo.

Global epidemiology of dental caries and severe periodontitis - a comprehensive review.

BACKGROUND: Dental caries and periodontitis are the most common oral diseases and major causes of tooth loss. AIM: To perform a review of global prevalence and incidence of dental caries and periodontitis. METHODOLOGY: Inclusion and exclusion criteria were developed. MEDLINE database and EMBASE database were used to search for eligible publications using keywords and MeSH terms. Additionally, WHO databank was used for obtaining dental caries information and PUBMED for a search on trends of dental caries prevalence and severity. RESULTS: Over the last four decades, the prevalence and severity of dentine carious lesions among 5- and 12-year-olds have declined; the decay-component is very high, with the lowest prevalence among 12-year-olds in high-income countries, which also had the lowest prevalence among 35- to 44-year-olds; and the number of retained teeth has increased around the globe. The prevalence of periodontitis is high, with approximately 10% of the global population affected by severe periodontitis. Study heterogeneity and methodological issues hamper comparisons across studies and over time. CONCLUSION: While the prevalence of dental caries has decreased, the disease is prevalent in all age groups. The prevalence of periodontitis is high. There is insufficient evidence to conclude that the prevalence of periodontitis has changed over time.

What's New in Dentine Bonding?: Universal Adhesives.

The ability to bond restorations to dentine successfully is central to minimally invasive restorative dentistry. While dentine-bonding agents have gone through a variety of 'generations', it is the purpose of this paper to describe the latest dentine-bonding agents, the Universal Bonding Agents. These materials may be considered 'Universal' insofar as they may be considered to be capable of being used for direct and indirect dentistry, as well as being suitable for use in whichever etching modality the clinician considers appropriate, namely self-etch, etch and rinse or selective enamel etch. Laboratory investigations and initial clinical studies hold the promise that Universal Bonding Agents are a forward step in the quest for the ultimate bond to tooth substance. Clinical relevance: New Universal Bonding Agents appear to present a promising advance in bonding to dentine.

Altered tooth morphogenesis after silencing the planar cell polarity core component, Vangl2.

Vangl2, one of the core components of the planar cell polarity (PCP) pathway, has an important role in the regulation of morphogenesis in several tissues. Although the expression of Vangl2 has been detected in the developing tooth, its role in tooth morphogenesis is not known. In this study, we show that Vangl2 is expressed in the inner dental epithelium (IDE) and in the secondary enamel knots (SEKs) of bell stage tooth germs. Inhibition of Vangl2 expression by siRNA treatment in in vitro-cultured tooth germs resulted in retarded tooth germ growth with deregulated cell proliferation and apoptosis. After kidney transplantation of Vangl2 siRNA-treated tooth germs, teeth were observed to be small and malformed. We also show that Vangl2 is required to maintain the proper pattern of cell alignment in SEKs, which maybe important for the function of SEKs as signaling centers. These results suggest that Vangl2 plays an important role in the morphogenesis of teeth.

Minimally Invasive Long-Term Management of Direct Restorations: the '5 Rs'.

The assessment and operative long-term management of direct restorations is a complex and controversial subject in conservative dentistry. Employing a minimally invasive (MI) approach helps preserve natural tooth structure and maintain endodontic health for as long as possible during the restorative cycle. This paper discusses how minimally invasive techniques may be applied practically to reviewing, resealing, refurbishing, repairing or replacing deteriorating/failed direct coronal restorations (the'5 Rs') and provides an update of contemporary MI clinical procedures. CPD/CLINICAL RELEVANCE: The assessment and long-term clinical management of deteriorating/failing direct restorations is a major component of the general dental practice workload and NHS UK budget expenditure for operative dentistry.

Evolving marine biomimetics for regenerative dentistry.

New products that help make human tissue and organ regeneration more effective are in high demand and include materials, structures and substrates that drive cell-to-tissue transformations, orchestrate anatomical assembly and tissue integration with biology. Marine organisms are exemplary bioresources that have extensive possibilities in supporting and facilitating development of human tissue substitutes. Such organisms represent a deep and diverse reserve of materials, substrates and structures that can facilitate tissue reconstruction within lab-based cultures. The reason is that they possess sophisticated structures, architectures and biomaterial designs that are still difficult to replicate using synthetic processes, so far. These products offer tantalizing pre-made options that are versatile, adaptable and have many functions for current tissue engineers seeking fresh solutions to the deficiencies in existing dental biomaterials, which lack the intrinsic elements of biofunctioning, structural and mechanical design to regenerate anatomically correct dental tissues both in the culture dish and in vivo.

Quantification of nanoparticle interactions in pure solvents and a concentrated PDMS solution as a function of solvent quality.

Using turbidity measurements, we quantified the interactions between PDMS-grafted silica nanoparticles (PDMS-g-silica) in pure solvents and a concentrated polymer solution with a focus on detecting the impact of solvent quality on graft layer stretching. This work is an extension of our previous work where we showed that interfacial wetting of the grafted polymer leads to depletion restabilization in semidilute and concentrated polymer solutions in good solvents (Dutta, N.; Green, D. Langmuir 2008, 24, 5260-5269). Subsequently, we showed that the criterion for depletion restabilization holds for both good and marginally poor solvents (Dutta, N.; Green, D. Langmuir 2010, 26, 16737-16744). In this work, we quantified nanoparticle interactions in terms of the second virial coefficient (B2), which captures the stretching of the brush in a good solvent in comparison to compression in a poor solvent. The transition from stretching to compression of the graft layer as a function of solvent quality was also supported by self-consistent mean-field (SCF) calculations. The PDMS-g-silica nanoparticles in a concentrated polymer solution in a good solvent within the complete wetting region behaved as though they were in a good solvent rather than in a polymer melt where on the basis of the SCF calculations the graft layers were expected to behave ideally. Overall, our results indicate that turbidity measurements can be used to determine the second virial coefficients for polymer-grafted nanoparticles in solvents and concentrated polymer solutions, and the relative values of the coefficients correspond well to those from theoretical calculations.

Degradation product emission from historic and modern books by headspace SPME/GC-MS: evaluation of lipid oxidation and cellulose hydrolysis.

Volatile organic compounds emitted from a several decade series of bound periodicals (1859-1939) printed on ground wood paper, as well as historical books dating from the 1500s to early 1800s made from cotton/linen rag, were studied using an improved headspace SPME/GC-MS method. The headspace over the naturally aging books, stored upright in glass chambers, was monitored over a 24-h period, enabling the identification of a wide range of organic compounds emanating from the whole of the book. The detection of particular straight chain aldehydes, as well as characteristic alcohols, alkenes and ketones is correlated with oxidative degradation of the C(18) fatty acid constituency of paper. The relative importance of hydrolytic and oxidative chemistry involved in paper aging in books published between 1560 and 1939 was examined by comparing the relative abundances of furfural (FUR) a known cellulose hydrolysis product, and straight chain aldehydes (SCA) produced from the oxidation of fatty acids in paper. The relative abundance of furfural is shown to increase across the 379-year publication time span. A comparison of relative SCA peak areas across the series of books examined reveals that SCA emission is more important in the cotton/linen rag books than in the ground wood books.

Contemporary adhesive bonding: bridging the gap between research and clinical practice.

UNLABELLED: The dawn of minimally invasive dentistry has led to the development of materials which rely on the use of effective adhesion to bond to remaining tooth tissue. Successful adhesive bonding is dependent upon appreciating the quality of the dental substrate, appropriate clinical handling of the material and patient, together with an appreciation of the chemistry of the adhesive. This paper outlines the current status of contemporary bonding, with particular emphasis on translating laboratory-based evidence into clinical practice. Using laboratory-based evidence, the ability of a bond to achieve a seal to enamel appears to be the best predictor of clinical performance. CLINICAL RELEVANCE: This article discusses the issues raised when translating research data about adhesive bonding from the laboratory to clinical dental practice.

Synthetic tissue engineering with smart, cytomimetic protocells.

Synthetic protocells are rudimentary origin-of-life versions of natural cell counterparts. Protocells are widely engineered to advance efforts and useful accepted outcomes in synthetic biology, soft matter chemistry and bioinspired materials chemistry. Protocells in collective symbiosis generate synthetic proto-tissues that display unprecedented autonomy and yield advanced materials with desirable life-like features for smart multi-drug delivery, micro bioreactors, renewable fuel production, environmental clean-up, and medicine. Current levels of protocell and proto-tissue functionality and adaptivity are just sufficient to apply them in tissue engineering and regenerative medicine, where they animate biomaterials and increase therapeutic cell productivity. As of now, structural biomaterials for tissue engineering lack the properties of living biomaterials such as self-repair, stochasticity, cell synergy and the sequencing of molecular and cellular events. Future protocell-based biomaterials provide these core properties of living organisms, but excluding evolution. Most importantly, protocells are programmable for a broad array of cell functions and behaviors and collectively in consortia are tunable for multivariate functions. Inspired by upcoming designs of smart protocells, we review their developmental background and cover the most recently reported developments in this promising field of synthetic proto-biology. Our emphasis is on manufacturing proto-tissues for tissue engineering of organoids, stem cell niches and reprogramming and tissue formation through stages of embryonic development. We also highlight the exciting reported developments arising from fusing living cells and tissues, in a valuable hybrid symbiosis, with synthetic counterparts to bring about novel functions, and living tissue products for a new synthetic tissue engineering discipline.

Impact of solvent quality on nanoparticle dispersion in semidilute and concentrated polymer solutions.

We investigated how solvent quality affects the stability of polymer-grafted nanoparticles in semidilute and concentrated polymer solutions, which extends our previous studies on these types of dispersions in good solvents [Langmuir 2008, 24, 5260-5269]. As discussed in the current article, dynamic light scattering (DLS) was used to quantify the diffusion of polydimethylsiloxane-grafted silica nanoparticles, or PDMS-g-silica, in bromocyclohexane as well as in PDMS/bromocyclohexane solutions. We established that bromocyclohexane is a theta solvent for PDMS by varying the temperature of the solutions with PDMS-g-silica nanoparticles and detecting their aggregation at a theta temperature of T(Θ) = 19.6 °C. Using this temperature as a benchmark for the transition between good and bad solvent conditions, further stability tests were carried out in semidilute and concentrated polymer solutions of PDMS in bromocyclohexane at T = 10-60 °C. Irrespective of temperature, i.e., solvent quality, we found that the nanoparticles dispersed uniformly when molecular weight of the graft polymer was greater than that of the free polymer. However, when the free polymer molecular weight was greater than that of the graft polymer, the nanoparticles aggregated. Visual studies were also used to confirm the correspondence between nanoparticle stability and graft and free polymer molecular weights in a wide range of marginally poor solvents with PDMS. Further, the correspondence between nanoparticle stability and instability with graft and free polymer molecular weight and solvent quality was also supported with self-consistent mean-field calculations. Thus, by relating experiment and theory, our results indicate that nanoparticle stability in semidilute and concentrated polymer solutions is governed by interactions between the graft and free polymers under conditions of variable solvency.

Transient facial nerve palsy following dental local anaesthesia.

Facial nerve palsy is a rare but known complication of dental local anaesthesia and may be underreported. We describe a case of a transient facial nerve palsy following the administration of an inferior alveolar nerve block and discuss the immediate practical management. Knowing the likely transient nature of this complication means the patient can be reassured and unnecessary referral avoided. While the blink reflex is inhibited, steps are needed in order to protect the cornea and prevent secondary infection and scarring.

A nanostructured anti-biofilm surface widens the efficacy against spindle-shaped and chain-forming rod-like bacteria.

Current control of pathogenic bacteria at all biomaterial interfaces is poorly attuned to a broad range of disease-causing pathogens. Leading antimicrobial surface functionalization strategies with antimicrobial peptides (AMPs), defensins, have not shown their promised efficacy. One of the main problems is the lack of stability and swift clearance from the surface. Surface nanotopography bearing sharp protrusions is a non-chemical solution that is intrinsically stable and long-lasting. Previously, the geometrically ordered arrays of nanotipped spines repelled or rapidly ruptured bacteria that come into contact. The killing properties so far work on cocci and rod-like bacteria, but there is no validation of the efficacy of protrusional surfaces on pathogenic bacteria with different sizes and morphologies, thus broadening the utility of such surfaces to cover increasingly more disease entities. Here, we report a synthetic analogue of nanotipped spines with a pyramidal shape that show great effectiveness on species of bacteria with strongly contrasting shapes and sizes. To highlight this phenomenon in the field of dental applications where selective bacterial control is vital to the clinical success of biomaterial functions, we modified the poly(methyl)-methacrylate (PMMA) texture and tested it against Streptococcus mutans, Enterococcus faecalis, Porphyromonas gingivalis, and Fusobacterium nucleatum. These nanopyramids performed effectively at levels well above those of normal and roughened PMMA biomaterials for dentistry and a model material for general use in medicine and disease transmission in hospital environments.

Enhanced NHS endodontic services in England: a postcode lottery?

Aim To investigate the consistency of commissioning and provision of enhanced NHS endodontic services across England.Methods The level of provision for enhanced endodontic services was sought using two methods. An electronic questionnaire was distributed to each of the thirteen director of commissioning operations (DCO) teams in NHS England to determine the perception from commissioners of what endodontic services are currently provided and commissioned. A systematic search to assess what is advertised by enhanced endodontic providers was also carried out to cross-reference with the information gained from electronic questionnaires.Results A 77% response rate to the questionnaire was achieved. Eight out of the ten DCO teams that replied provided enhanced NHS endodontics to a greater or lesser extent, one did not and one was unsure. Three teams did not respond. Providers of services included dentists with enhanced skills, endodontic specialists, and dentists working within district or dental hospitals. Five out of ten DCO teams commissioned level two services and six commissioned level three services. Dental hospital acceptance criteria for enhanced endodontics differ regionally, but most accept level three and some level two complexity treatments, depending upon capacity at the time.Conclusions This investigation demonstrates that although the majority of NHS commissioning areas within England provide enhanced endodontic services, these are not the same across the country. Therefore, patients are not getting equal access to services and it may vary depending upon location.

Developing palatal bone using human mesenchymal stem cell and stem cells from exfoliated deciduous teeth cell sheets.

Cleft palate is one of the most common craniofacial defects in newborn babies. The characteristics of this genetic disease produce soft and hard tissue defects on the lip and maxilla, which cause not only aesthetic but also functional problems with speech, eating, and breathing. Bone grafts using autologous cancellous bone have been a standard treatment to repair the hard tissue defect in cleft palates. However, such grafts do not fully integrate into host bone and undergo resorption. To overcome engraftment problems, it is common to engineer new tissues with a combination of multipotent cells and biomaterial frameworks. Here, we manufactured cell sheets for bone repair of cleft palates derived from two osteogenic cell sources, human mesenchymal stem cells (hMSCs) and stem cells from human exfoliated deciduous teeth (SHEDs). Cell sheets made from hMSCs and SHEDs gave rise to in vitro calcification, which indicated the osteogenic potential of these cells. The cell sheets of hMSCs and SHEDs expressed the bone-specific osteogenic markers, osterix, osteocalcin, and osteopontin, following insertion into ex vivo-cultured embryonic palatal shelves and in ovo culture. In conclusion, we showed that osteogenic stem cell sheets have mineralization potential and might represent a new alternative to autologous bone transplantation in the reconstruction of cleft palates.

Increases in inspiratory neural drive in response to rapid oscillating airflow braking forces (vibration).

OBJECTIVE: To investigate whether 10 breaths against a vibration stimulus elicits increments of spontaneous and maximal inspiratory mouth pressure (maxMP) and tidal mean inspiratory flow (iV(T)/T(I)) upon stimulus removal. METHODS: Twelve healthy subjects (8 female, 4 male; 22-50 years old), recruited from the University student body, completed 3 maximal inspirations before (pre) and after (post) 10 inspirations against resistive loading with a vibration-type stimulus (VIB; youbreathe, Exoscience Ltd., London, UK), pressure-matched resistive loading (RES) or resting breathing (CON; no load). The trials were presented in a random order. maxMP and involuntary tidal breathing were compared pre and post conditioning. RESULTS: Inspiratory neural drive increased only after VIB as evidenced by increased tidal and maxMP and mean inspiratory flow (iV(T)/T(I); p < 0.05). There was no effect of either resistance or control breathing on maximal maxMP or tidal responses. CONCLUSIONS: Ten conditioning breaths of VIB lead to increased maximal inspiratory mouth pressure and spontaneous mouth pressure and mean inspiratory flow possibly through a common mechanism of increased descending respiratory drive.