Lithiated porous silicon nanowires stimulate periodontal regeneration.

Periodontal disease is a significant burden for oral health, causing progressive and irreversible damage to the support structure of the tooth. This complex structure, the periodontium, is composed of interconnected soft and mineralised tissues, posing a challenge for regenerative approaches. Materials combining silicon and lithium are widely studied in periodontal regeneration, as they stimulate bone repair via silicic acid release while providing regenerative stimuli through lithium activation of the Wnt/ß-catenin pathway. Yet, existing materials for combined lithium and silicon release have limited control over ion release amounts and kinetics. Porous silicon can provide controlled silicic acid release, inducing osteogenesis to support bone regeneration. Prelithiation, a strategy developed for battery technology, can introduce large, controllable amounts of lithium within porous silicon, but yields a highly reactive material, unsuitable for biomedicine. This work debuts a strategy to lithiate porous silicon nanowires (LipSiNs) which generates a biocompatible and bioresorbable material. LipSiNs incorporate lithium to between 1% and 40% of silicon content, releasing lithium and silicic acid in a tailorable fashion from days to weeks. LipSiNs combine osteogenic, cementogenic and Wnt/ß-catenin stimuli to regenerate bone, cementum and periodontal ligament fibres in a murine periodontal defect.

The effect of location/site on polished human enamel after mechanical and chemical wear.

OBJECTIVE: To compare profilometry and microhardness of polished occlusal and buccal human enamel following a mechanical and chemical wear regime. METHODS: Enamel from polished human molars were sectioned into buccal and occlusal surfaces and randomly allocated into two groups (n = 10) and then exposed to 0.3 % citric acid at pH 2.7 for 10, 20, 40 and 60 mins each followed by abrasion with non-fluoridated toothpaste for 240 strokes in a reciprocating brushing machine. A white light profilometer with a spot size of 12 um measured mean step-height following each cycle. Microhardness indentations were conducted following the final cycled 60 mins erosion/abrasion using 0.01, 0.02, 0.1, 0.5 and 2.5 kgf indentation load. Statistical disparity were evaluated using a two-way ANOVA and post-hoc Sidak's multiple comparisons tests at α = 0.05. RESULTS: After erosion/abrasion, the mean (SD) step-heights on occlusal and buccal surfaces were not significantly different until 60 mins, when occlusal surfaces exhibited greater step-heights, 32.9 µm (2.8) and 31.1 µm (1.8) and p = 0.02, respectively. Buccal and occlusal microhardness was statistically lower following erosion/abrasion at loads of 0.01 kgf (p = 0.0005) and 0.02 kgf (p = 0.0006) but no significant differences were observed in the microhardness between the surfaces at any loads. CONCLUSION: The occlusal and buccal surfaces were not statistically different for microhardness or step height suggesting the susceptibility to wear is not related to the anatomy and structure of the tooth and is more likely related to other factors such as the environment. CLINICAL SIGNIFICANCE: The study emphasizes that a notable difference in wear between occlusal and buccal enamel surfaces emerges only after prolonged exposure to simultaneous chemical and mechanical stress. This finding necessitates a preventive dental approach that accounts for both the duration of exposure and environmental factors.

A novel method for simulating ex vivo tooth extractions under varying applied loads.

BACKGROUND: Tooth extraction is a common surgical procedure where the invasiveness of the surgery can affect the nature of the dentoalveolar remodelling which follows. However, there is very little biomechanical data relating the loading applied during tooth extraction to the outcomes of the procedure. The purpose of this pilot study is to present a novel ex vivo experimental method for measuring tooth extraction mechanics and to explore preliminary metrics for predicting extraction success. METHODS: A custom experimental apparatus was developed in-house to extract central incisors from ex vivo swine mandible samples. Twenty-five (n = 25) incisors were extracted at different rates in displacement- and force-control, along with an intermittent ramp-hold scheme for a total of five schemes. Peak forces and extraction success were recorded for each test. Video analysis assisted in determining the instantaneous stiffnesses of the dental complex during continuous extractions, which were compared using the K-means clustering algorithm. FINDINGS: Tooth extraction forces ranged from 102 N to 309 N, with higher-rate tests tending towards higher peak forces (141 N - 308 N) than the lower-rate tests (102 N-204 N) for displacement- and force-controlled schemes. The K-means algorithm clearly identified load rates among tests, indicating that higher-rate loading increased system stiffness relative to the lower-rate tests. INTERPRETATION: The developed experimental method demonstrated a desirable degree of control. The preliminary results suggest the influence of load rate on the mechanical response of the dental complex and extraction outcome. Future work will further investigate the biomechanics of tooth extraction and relate them to tissue damage to improve future tooth extraction procedures.

Addressing uncertainties in correlative imaging of exogenous particles with the tissue microanatomy with synchronous imaging strategies.

Exposure to exogenous particles is of increasing concern to human health. Characterizing the concentrations, chemical species, distribution, and involvement of the stimulus with the tissue microanatomy is essential in understanding the associated biological response. However, no single imaging technique can interrogate all these features at once, which confounds and limits correlative analyses. Developments of synchronous imaging strategies, allowing multiple features to be identified simultaneously, are essential to assess spatial relationships between these key features with greater confidence. Here, we present data to first highlight complications of correlative analysis between the tissue microanatomy and elemental composition associated with imaging serial tissue sections. This is achieved by assessing both the cellular and elemental distributions in three-dimensional space using optical microscopy on serial sections and confocal X-ray fluorescence spectroscopy on bulk samples, respectively. We propose a new imaging strategy using lanthanide-tagged antibodies with X-ray fluorescence spectroscopy. Using simulations, a series of lanthanide tags were identified as candidate labels for scenarios where tissue sections are imaged. The feasibility and value of the proposed approach are shown where an exposure of Ti was identified concurrently with CD45 positive cells at sub-cellular resolutions. Significant heterogeneity in the distribution of exogenous particles and cells can be present between immediately adjacent serial sections showing a clear need of synchronous imaging methods. The proposed approach enables elemental compositions to be correlated with the tissue microanatomy in a highly multiplexed and non-destructive manner at high spatial resolutions with the opportunity for subsequent guided analysis.

Pre-cementation treatment of glass-ceramics with vacuum impregnated resin coatings.

OBJECTIVE: The study aimed to investigate the effectiveness of a vacuum impregnation process to eliminate the porosity at the ceramic-resin interface to optimize the reinforcement of a glass-ceramic by resin cementation. METHODS: 100 leucite glass-ceramic disks (1.0 ± 0.1 mm thickness) were air-abraded, etched with 9.6 % HF acid, and silanated. Specimens were randomly allocated to 5 groups (n = 20). Group A received no further treatment (uncoated control). Groups B and D were resin-coated under atmospheric pressure, whereas groups C and E were resin-coated using vacuum impregnation. The polymerized resin-coating surfaces of specimens in groups B and C were polished to achieve a resin thickness of 100 ± 10 µm, while in groups D and E no resin-coating modification was performed prior to bi-axial flexure strength (BFS) determination. Optical microscopy was undertaken on the fracture fragments to identify the failure mode and origin. Comparisons of BFS group means were made by a one-way analysis of variance (ANOVA) and post-hoc Tukey test at α = 0.05. RESULTS: All resin-coated sample groups (B-E) showed a statistically significant increase in mean BFS compared with the uncoated control (p < 0.01). There was a significant difference in BFS between the ambient and vacuum impregnated unpolished groups (D and E) (p < 0.01), with the greatest strengthening achieved using a vacuum impregnation technique. SIGNIFICANCE: Results highlight the opportunity to further develop processes to apply thin conformal resin coatings, applied as a pre-cementation step to strengthen dental glass-ceramics.

Prosthodontic complications during implant-based oral rehabilitation of patients with head and neck cancer.

STATEMENT OF PROBLEM: Implant-retained prosthodontic rehabilitation of patients with head and neck cancer is complex. However, the extent of prosthodontic complications has been sparsely reported within the literature. PURPOSE: The purpose of this retrospective study was to describe the range of complications and issues that affected the oral rehabilitation treatment of patients with head and neck cancer who had completed implant-retained prosthodontic rehabilitation in a tertiary treatment center. MATERIAL AND METHODS: A retrospective analysis of complications and their consequences in patients treated in a regional unit from 2012 to 2017 was performed. Descriptive analysis was carried out on the type and frequency of complications and their consequences for the patients' treatment. Complications were grouped into the following complication types: local and systemic, implant, peri-implant soft tissue, and clinical prosthodontic complications. Implant success and implant survival were also reported. RESULTS: The sample was composed of 163 patients with head and neck cancer who had completed implant-retained prosthodontic rehabilitation. Local and systemic complications affected 8.6% of patients, and peri-implant soft-tissue complications affected 9.8% of patients. Clinical prosthodontic complications leading to repeated clinical or laboratory stages occurred on 48 occasions in 45 patients (27.6% of patients). A total of 763 implants were placed. Implant survival was 95.8% and implant success 94.5%, with a mean follow-up of 42.1 months. CONCLUSIONS: This retrospective evaluation indicated that complications arising during the process of implant-retained prosthetic rehabilitation in this patient group were variable and common. Such complications can delay the process of treatment and lead to repeating or restarting clinical and laboratory stages of treatment.

Extracellular Matrix Profiling and Disease Modelling in Engineered Vascular Smooth Muscle Cell Tissues.

Aortic smooth muscle cells (SMCs) have an intrinsic role in regulating vessel homeostasis and pathological remodelling. In two-dimensional (2D) cell culture formats, however, SMCs are not embedded in their physiological extracellular matrix (ECM) environment. To overcome the limitations of conventional 2D SMC cultures, we established a 3D in vitro model of engineered vascular smooth muscle cell tissues (EVTs). EVTs were casted from primary murine aortic SMCs by suspending a SMC-fibrin master mix between two flexible silicon-posts at day 0 before prolonged culture up to 14 days. Immunohistochemical analysis of EVT longitudinal sections demonstrated that SMCs were aligned, viable and secretory. Mass spectrometry-based proteomics analysis of murine EVT lysates was performed and identified 135 matrisome proteins. Proteoglycans, including the large aggregating proteoglycan versican, accumulated within EVTs by day 7 of culture. This was followed by the deposition of collagens, elastin-binding proteins and matrix regulators up to day 14 of culture. In contrast to 2D SMC controls, accumulation of versican occurred in parallel to an increase in versikine, a cleavage product mediated by proteases of the A Disintegrin and Metalloproteinase with Thrombospondin motifs (ADAMTS) family. Next, we tested the response of EVTs to stimulation with transforming growth factor beta-1 (TGFß-1). EVTs contracted in response to TGFß-1 stimulation with altered ECM composition. In contrast, treatment with the pharmacological activin-like kinase inhibitor (ALKi) SB 431542 suppressed ECM secretion. As a disease stimulus, we performed calcification assays. The ECM acts as a nidus for calcium phosphate deposition in the arterial wall. We compared the onset and extent of calcification in EVTs and 2D SMCs cultured under high calcium and phosphate conditions for 7 days. Calcified EVTs displayed increased tissue stiffness by up to 30 % compared to non-calcified controls. Unlike the rapid calcification of SMCs in 2D cultures, EVTs sustained expression of the calcification inhibitor matrix Gla protein and allowed for better discrimination of the calcification propensity between independent biological replicates. In summary, EVTs are an intuitive and versatile model to investigate ECM synthesis and turnover by SMCs in a 3D environment. Unlike conventional 2D cultures, EVTs provide a more relevant pathophysiological model for retention of the nascent ECM produced by SMCs.

Surface Free Energy Dominates the Biological Interactions of Postprocessed Additively Manufactured Ti-6Al-4V.

Additive manufacturing (AM) has emerged as a disruptive technique within healthcare because of its ability to provide personalized devices; however, printed metal parts still present surface and microstructural defects, which may compromise mechanical and biological interactions. This has made physical and/or chemical postprocessing techniques essential for metal AM devices, although limited fundamental knowledge is available on how alterations in physicochemical properties influence AM biological outcomes. For this purpose, herein, powder bed fusion Ti-6Al-4V samples were postprocessed with three industrially relevant techniques: polishing, passivation, and vibratory finishing. These surfaces were thoroughly characterized in terms of roughness, chemistry, wettability, surface free energy, and surface ζ-potential. A significant increase in Staphylococcus epidermidis colonization was observed on both polished and passivated samples, which was linked to high surface free energy donor γ- values in the acid-base, γAB component. Early osteoblast attachment and proliferation (24 h) were not influenced by these properties, although increased mineralization was observed for both these samples. In contrast, osteoblast differentiation on stainless steel was driven by a combination of roughness and chemistry. Collectively, this study highlights that surface free energy is a key driver between AM surfaces and cell interactions. In particular, while low acid-base components resulted in a desired reduction in S. epidermidis colonization, this was followed by reduced mineralization. Thus, while surface free energy can be used as a guide to AM device development, optimization of bacterial and mammalian cell interactions should be attained through a combination of different postprocessing techniques.

Survival rate and complication-free survival rate of implant-retained prostheses in the oral rehabilitation of patients with head and neck cancer: A retrospective evaluation of a cohort from a regional service.

STATEMENT OF PROBLEM: Literature reporting on the prosthetic survival and complications of implant-retained prostheses in patients with head and neck cancer is sparse. PURPOSE: The purpose of this retrospective study was to present the survival rates and complication-free survival rates of both fixed and removable implant-retained oral prostheses in patients with head and neck cancer while also reporting on the frequency and causes of failure and complications for each prosthesis type. MATERIAL AND METHODS: A retrospective analysis of the prosthetic survival rates and complication-free survival rates of implant-retained oral prostheses and the frequency and causes of failure and complications in patients with head and neck cancer treated in a regional unit from 2012 to 2017 was performed. Differences in categorical and continuous data were assessed for statistical significance by using the Pearson chi-square test, Fisher exact test, t test, and analysis of variance as appropriate. Cox proportional hazard regression models were fitted to evaluate the association between prostheses type, clinical and medical factors, and the outcomes of survival and complication-free survival. Descriptive statistics were used to analyze the frequency and type of prosthetic complications. RESULTS: The sample was composed of 153 patients diagnosed with head and neck cancer who had completed implant-retained prosthodontic rehabilitation and had been provided with 221 prostheses. The 5-year survival rate was 87% for maxillary fixed prostheses, 79% for mandibular fixed, 66% for maxillary removable, and 50% for mandibular removable. Hazard ratios were calculated showing that the 5-year survival rate of a mandibular removable prosthesis (HR=5.1; 95% CI 1.60-16.25) (P=.006) was greater than that of a maxillary fixed prosthesis (HR=1.0). The 5-year complication-free survival rate was highest for mandibular fixed prostheses (62%), followed by maxillary fixed (58%), maxillary removable (36%), and mandibular removable prostheses (29%). Hazard ratios showed that the 5-year survival rate of maxillary removable (HR=1.91; 95% CI 1.01-3.66) (P=.048) and mandibular removable prosthesis (HR=2.29; 95% CI 1.23-4.25) (P=.009) was greater than that of a maxillary fixed prosthesis (HR=1.0). Variables of radiotherapy, grafting, age, and sex and their influence on the survival rate and complication-free survival rate were assessed but were not statistically significant. CONCLUSIONS: This evaluation indicated that fixed implant-retained prostheses had a higher 5-year survival rate and 5-year complication-free survival rate than removable implant-retained prostheses in patients with head and neck cancer.

Impurities in commercial titanium dental implants - A mass and optical emission spectrometry elemental analysis.

OBJECTIVE: Titanium (Ti) is considered bioinert and is still regarded as the "gold standard" material for dental implants. However, even 'commercial pure' Ti will contain minor fractions of elemental impurities. Evidence demonstrating the release of Ti ions and particles from 'passive' implant surfaces is increasing and has been attributed to biocorrosion processes which may provoke immunological reactions. However, Ti observed in peri-implant tissues has been shown to be co-located with elements considered impurities in biomedical alloys. Accordingly, this study aimed to quantify the composition of impurities in commercial Ti dental implants. METHODS: Fifteen commercial titanium dental implant systems were analyzed using inductively coupled plasma-mass spectrometry (ICP-MS) and optical emission spectrometry (ICP-OES). RESULTS: The elemental composition of implants manufactured from commercially pure grades of Ti, Ti-6Al-4V, and the TiZr alloy (Roxolid) conformed to the respective ISO/ASTM standards or manufacturers´ data (TiZr/Roxolid). However, all implants investigated included exogenous metal contaminants including Ni, Cr, Sb, and Nb to a variable extent. Other contaminants detected in a fraction of implants included As and the radionuclides U-238 and Th-232. SIGNIFICANCE: Although all Ti implant studies conformed with their standard compositions, potentially allergenic, noxious metals and even radionuclides were detected. Since there are differences in the degree of contamination between the implant systems, a certain impurity fraction seems technically avoidable. The clinical relevance of these findings must be further investigated, and an adaptation of industry standards should be discussed.

Local depletion of proteoglycans mediates cartilage tissue repair in an ex vivo integration model.

Successfully replacing damaged cartilage with tissue-engineered constructs requires integration with the host tissue and could benefit from leveraging the native tissue's intrinsic healing capacity; however, efforts are limited by a poor understanding of how cartilage repairs minor defects. Here, we investigated the conditions that foster natural cartilage tissue repair to identify strategies that might be exploited to enhance the integration of engineered/grafted cartilage with host tissue. We damaged porcine articular cartilage explants and using a combination of pulsed SILAC-based proteomics, ultrastructural imaging, and catabolic enzyme blocking strategies reveal that integration of damaged cartilage surfaces is not driven by neo-matrix synthesis, but rather local depletion of proteoglycans. ADAMTS4 expression and activity are upregulated in injured cartilage explants, but integration could be reduced by inhibiting metalloproteinase activity with TIMP3. These observations suggest that catabolic enzyme-mediated proteoglycan depletion likely allows existing collagen fibrils to undergo cross-linking, fibrillogenesis, or entanglement, driving integration. Catabolic enzymes are often considered pathophysiological markers of osteoarthritis. Our findings suggest that damage-induced upregulation of metalloproteinase activity may be a part of a healing response that tips towards tissue destruction under pathological conditions and in osteoarthritis, but could also be harnessed in tissue engineering strategies to mediate repair. STATEMENT OF SIGNIFICANCE: Cartilage tissue engineering strategies require graft integration with the surrounding tissue; however, how the native tissue repairs minor injuries is poorly understood. We applied pulsed SILAC-based proteomics, ultrastructural imaging, and catabolic enzyme blocking strategies to a porcine cartilage explant model and found that integration of damaged cartilage surfaces is driven by catabolic enzyme-mediated local depletion of proteoglycans. Although catabolic enzymes have been implicated in cartilage destruction in osteoarthritis, our findings suggest that damage-induced upregulation of metalloproteinase activity may be a part of a healing response that tips towards tissue destruction under pathological conditions. They also suggest that this natural cartilage tissue repair process could be harnessed in tissue engineering strategies to enhance the integration of engineered cartilage with host tissue.

Cranial suture morphometry and mechanical response to loading: 2D vs. 3D assumptions and characterization.

Cranial sutures are complex soft tissue structures whose mechanics are often studied due to their link with bone growth in the skull. Researchers will often use a cross-sectional two-dimensional slice to define suture geometry when studying morphometry and/or mechanical response to loading. However, using a single cross section neglects the full suture complexity and may introduce significant errors when defining their form. This study aims to determine trends in suture path variability through skull thickness in a swine model and the implications of using a 'representative' cross section on mechanical modeling. To explore these questions, a mixture of quantitative analysis of computed tomography images and finite element models was used. The linear interdigitation and width of coronal and sagittal sutures were analyzed on offset transverse planes through the skull thickness. It was found that sagittal suture width and interdigitation were largely consistent through the skull thickness, whereas the coronal suture showed significant variation in both. The finite element study found that average values of displacement and strain were similar between the two-dimensionally variable and three-dimensionally variable models. Larger ranges and more complex distributions of strain were found in the three-dimensionally variable model. Outcomes of this study indicate that the appropriateness of using a representative cross section to describe suture morphometry and predict mechanical response should depend on specific research questions and goals. Two-dimensional approximations can be sufficient for less-interdigitated sutures and when bulk site mechanics are of interest, while taking the true three-dimensional geometry into account is necessary when considering spatial variability and local mechanical response.

Malignant Transformation Rate of Oral Submucous Fibrosis: A Systematic Review and Meta-Analysis.

Oral submucous fibrosis (OSF) is a chronic progressive condition affecting the oral cavity, oropharynx and upper third of the oesophagus. It is a potentially malignant disorder. The authors collated and analysed the existing literature to establish the overall malignant transformation rate (MTR). A retrospective analysis of medical and dental scientific literature using online indexed databases was conducted for the period 1956 to 2021. The quality of the enrolled studies was assessed by the Newcastle-Ottawa Scale (NOS). A meta-analysis using a random effects model of a single proportion was performed along with statistical tests for heterogeneity. The overall proportion of malignancy across all studies was 0.06 (95% CI, 0.02-0.10), indicating an overall 6% risk of malignant transformation across all studies and cohorts. Sub-group analyses revealed strong differences in proportion of malignancy according to ethnicity/cohort; Chinese = 0.02 (95% CI 0.01-0.02), Taiwanese = 0.06 (95% CI, 0.03-0.10), Indian = 0.08 (95% CI, 0.03-0.14) and Pakistani = 0.27 (95% CI 0.25-0.29). Overall, the MTR was 6%; however, wide heterogeneity of the included studies was noted. Geographic variations in MTR were noted but were not statistically significant. Further studies are required to analyse the difference between cohort groups.

A feasible route for the design and manufacture of customised respiratory protection through digital facial capture.

The World Health Organisation has called for a 40% increase in personal protective equipment manufacturing worldwide, recognising that frontline workers need effective protection during the COVID-19 pandemic. Current devices suffer from high fit-failure rates leaving significant proportions of users exposed to risk of viral infection. Driven by non-contact, portable, and widely available 3D scanning technologies, a workflow is presented whereby a user's face is rapidly categorised using relevant facial parameters. Device design is then directed down either a semi-customised or fully-customised route. Semi-customised designs use the extracted eye-to-chin distance to categorise users in to pre-determined size brackets established via a cohort of 200 participants encompassing 87.5% of the cohort. The user's nasal profile is approximated to a Gaussian curve to further refine the selection in to one of three subsets. Flexible silicone provides the facial interface accommodating minor mismatches between true nasal profile and the approximation, maintaining a good seal in this challenging region. Critically, users with outlying facial parameters are flagged for the fully-customised route whereby the silicone interface is mapped to 3D scan data. These two approaches allow for large scale manufacture of a limited number of design variations, currently nine through the semi-customised approach, whilst ensuring effective device fit. Furthermore, labour-intensive fully-customised designs are targeted as those users who will most greatly benefit. By encompassing both approaches, the presented workflow balances manufacturing scale-up feasibility with the diverse range of users to provide well-fitting devices as widely as possible. Novel flow visualisation on a model face is presented alongside qualitative fit-testing of prototype devices to support the workflow methodology.

Repeated exposure of nosocomial pathogens to silver does not select for silver resistance but does impact ciprofloxacin susceptibility.

The rise of antimicrobial resistant bacteria coupled with a void in antibiotic development marks Antimicrobial Resistance as one of the biggest current threats to modern medicine. Antimicrobial metals are being developed and used as alternative anti-infectives, however, the existence of known resistance mechanisms and limited data regarding bacterial responses to long-term metal exposure are barriers to widespread implementation. In this study, a panel of reference and clinical strains of major nosocomial pathogens were subjected to serial dosage cycles of silver and ciprofloxacin. Populations exposed to silver initially showed no change in sensitivity, however, increasingly susceptibility was observed after the 25th cycle. A control experiment with ciprofloxacin revealed a selection for resistance over time, with silver treated bacteria showing faster adaptation. Morphological analysis revealed filamentation in Gram negative species suggesting membrane perturbation, while sequencing of isolated strains identified mutations in numerous genes. These included those encoding for efflux systems, chemosensory systems, stress responses, biofilm formation and respiratory chain processes, although no consistent locus was identified that correlated with silver sensitivity. These results suggest that de novo silver resistance is hard to select in a range of nosocomial pathogens, although silver exposure may detrimentally impact sensitivity to antibiotics in the long term. STATEMENT OF SIGNIFICANCE: The adaptability of microbial life continuously calls for the development of novel antibiotic molecules, however, the cost and risk associated with their discovery have led to a drying up in the pipeline, causing antimicrobial resistance (AMR) to be a major threat to healthcare. From all available strategies, antimicrobial metals and, more specifically, silver showcase large bactericidal spectrum and limited toxic effect which coupled with a large range of processes available for their delivery made these materials as a clear candidate to tackle AMR. Previous reports have shown the ability of this metal to enact a synergistic effect with other antimicrobial therapies, nevertheless, the discovery of Ag resistance mechanisms since the early 70s and limited knowledge on the long term influence of silver on AMR poses a threat to their applicability. The present study provides quantitative data on the influence of silver based therapies on AMR development for a panel of reference and clinical strains of major nosocomial pathogens, revealing that prolonged silver exposure may detrimentally impact sensitivity to antibiotics.

More than the Eye Can See: Shedding New Light on SARS-CoV-2 Lateral Flow Device-Based Immunoassays.

Containing the global severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has been an unprecedented challenge due to high horizontal transmissivity and asymptomatic carriage rates. Lateral flow device (LFD) immunoassays were introduced in late 2020 to detect SARS-CoV-2 infection in asymptomatic or presymptomatic individuals rapidly. While LFD technologies have been used for over 60 years, their widespread use as a public health tool during a pandemic is unprecedented. By the end of 2020, data from studies into the efficacy of the LFDs emerged and showed these point-of-care devices to have very high specificity (ability to identify true negatives) but inadequate sensitivity with high false-negative rates. The low sensitivity (<50%) shown in several studies is a critical public health concern, as asymptomatic or presymptomatic carriers may wrongly be assumed to be noninfectious, posing a significant risk of further spread in the community. Here, we show that the direct visual readout of SARS-CoV-2 LFDs is an inadequate approach to discriminate a potentially infective viral concentration in a biosample. We quantified significant immobilized antigen-antibody-labeled conjugate complexes within the LFDs visually scored as negative using high-sensitivity synchrotron X-ray fluorescence imaging. Correlating quantitative X-ray fluorescence measurements and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) determined numbers of viral copies, we identified that negatively scored samples could contain up to 100 PFU (equivalent here to ∼10 000 RNA copies/test). The study demonstrates where the shortcomings arise in many of the current direct-readout SARS-CoV-2 LFDs, namely, being a deficiency in the readout as opposed to the potential level of detection of the test, which is orders of magnitude higher. The present findings are of importance both to public health monitoring during the Coronavirus Disease 2019 (COVID-19) pandemic and to the rapid refinement of these tools for immediate and future applications.

Strength-limiting damage and its mitigation in CAD-CAM zirconia-reinforced lithium-silicate ceramics machined in a fully crystallized state.

OBJECTIVES: The objective was to explore how clinically relevant machining process and heat treatment influence damage accumulation and strength degradation in lithium silicate-based glass ceramics machined in the fully crystallized state. METHODS: A commercial zirconia-reinforced lithium silicate (ZLS) glass ceramic with a fully developed microstructure (Celtra® Duo) was studied. Disk-shaped specimens (nominal 10 mm diameter and 1 mm thickness) were fabricated either using a CAD-CAM process, creating a clinically relevant dental restoration surface, or were sectioned from water-jet cut cylindrical blocks with their critical surfaces consistently polished. Bi-axial flexure strength (BFS) was determined in a ball-on-ring configuration, and fractographic analysis was performed on failed specimens. XRD, AFM and SEM measurements were conducted before and after heat treatment. For each sample group, BFS was correlated with surface roughness. A two-way ANOVA and post-hoc Tukey tests were used to determine differences in BFS between machining and heat treatment groups (ɑ = 0.05). RESULTS: A two-way ANOVA demonstrated that BFS was influenced by fabrication route (p < 0.01) with CAD-CAM specimens exhibiting significantly lower mean BFS. A factorial interaction was observed between heat treatment and machining route (p < 0.01), where a significant strengthening effect of post-manufacture heat treatment was noted for CAD-CAM specimens but not sectioned and polished samples. CAD-CAM specimens exhibited sub-surface lateral cracks alongside radial cracks near fracture origin which were not observed for polished specimens. BFS did not correlate with surface roughness for polished specimens, and no change in microstructure was detectable by XRD following heat treatment. SIGNIFICANCE: The mechanical properties of the ZLS ceramic material studied were highly sensitive to the initial surface defect integral associated with manufacturing route and order of operations. CAD-CAM manufacturing procedures result in significant strength-limiting damage which is likely to influence restoration performance; however, this can be partially mitigated by post-machining heat treatment.

Distribution and Chemical Speciation of Exogenous Micro- and Nanoparticles in Inflamed Soft Tissue Adjacent to Titanium and Ceramic Dental Implants.

Degradation of the implant surface and particle release/formation as an inflammation catalyst mechanism is an emerging concept in dental medicine that may help explain the pathogenesis of peri-implantitis. The aim of the present study was a synchrotron-based characterization of micro- and nanosized implant-related particles in inflamed human tissues around titanium and ceramic dental implants that exhibited signs of peri-implantitis. Size, distribution, and chemical speciation of the exogenous micro- and nanosized particle content were evaluated using synchrotron µ-X-ray fluorescence spectroscopy (XRF), nano-XRF, and µ-X-ray absorption near-edge structure (XANES). Titanium particles, with variable speciation, were detected in all tissue sections associated with titanium implants. Ceramic particles were found in five out of eight tissue samples associated with ceramic implants. Particles ranged in size from micro- to nanoscale. The local density of both titanium and ceramic particles was calculated to be as high as ∼40 million particles/mm3. µ-XANES identified titanium in predominantly two different chemistries, including metallic and titanium dioxide (TiO2). The findings highlight the propensity for particle accumulation in the inflamed tissues around dental implants and will help in guiding toxicological studies to determine the biological significance of such exposures.

A call for action to the biomaterial community to tackle antimicrobial resistance.

The global surge of antimicrobial resistance (AMR) is a major concern for public health and proving to be a key challenge in modern disease treatment, requiring action plans at all levels. Microorganisms regularly and rapidly acquire resistance to antibiotic treatments and new drugs are continuously required. However, the inherent cost and risk to develop such molecules has resulted in a drying of the pipeline with very few compounds currently in development. Over the last two decades, efforts have been made to tackle the main sources of AMR. Nevertheless, these require the involvement of large governmental bodies, further increasing the complexity of the problem. As a group with a long innovation history, the biomaterials community is perfectly situated to push forward novel antimicrobial technologies to combat AMR. Although this involvement has been felt, it is necessary to ensure that the field offers a united front with special focus in areas that will facilitate the development and implementation of such systems. This paper reviews state of the art biomaterials strategies striving to limit AMR. Promising broad-spectrum antimicrobials and device modifications are showcased through two case studies for different applications, namely topical and implantables, demonstrating the potential for a highly efficacious physical and chemical approach. Finally, a critical review on barriers and limitations of these methods has been developed to provide a list of short and long-term focus areas in order to ensure the full potential of the biomaterials community is directed to helping tackle the AMR pandemic.

Origin of micro-scale heterogeneity in polymerisation of photo-activated resin composites.

Photo-activated resin composites are widely used in industry and medicine. Despite extensive chemical characterisation, the micro-scale pattern of resin matrix reactive group conversion between filler particles is not fully understood. Using an advanced synchrotron-based wide-field IR imaging system and state-of-the-art Mie scattering corrections, we observe how the presence of monodispersed silica filler particles in a methacrylate based resin reduces local conversion and chemical bond strain in the polymer phase. Here we show that heterogeneity originates from a lower converted and reduced bond strain boundary layer encapsulating each particle, whilst at larger inter-particulate distances light attenuation and monomer mobility predominantly influence conversion. Increased conversion corresponds to greater bond strain, however, strain generation appears sensitive to differences in conversion rate and implies subtle distinctions in the final polymer structure. We expect these findings to inform current predictive models of mechanical behaviour in polymer-composite materials, particularly at the resin-filler interface.