In vitro remineralization by various ion-releasing materials of artificially demineralized dentin: A micro-CT study.

OBJECTIVE: The aim of this study was to evaluate the remineralizing properties of ion-releasing restorative materials on pH cycling-induced carious dentin. METHODS: Fifty sound molars were freshly extracted. The occlusal surfaces were abraded using water-cooled sandpaper (800 grit). The residual crowns were embedded in self-cured acrylic resin with the flat dentin surface exposed. A mesio-distal trench was created using a calibrated 0.5 mm deep occlusal reduction burr, and artificial dentin caries were generated by pH cycling. Then, teeth were randomly assigned to five groups according to the ion-releasing material used. For each sample, micro-CT acquisitions were performed at various intervals. Remineralization was assessed by mean gray value (MGV) measurements after registration and segmentation of the region of interest with 3D Slicer software. One-way repeated-measures ANOVA followed by Tukey's post hoc test was used to investigate the difference in MGVs among the various groups. RESULTS: Only Cention Forte showed significantly increased MGVs after 4 weeks compared to demineralized dentin. MGVs were higher, but not significantly, after placement of the restorative materials, including in the resin composite control group. These results can be explained by the radiopacity of the materials. SIGNIFICANCE: Cention Forte, the material with the highest radiopacity, showed a significant increase in the MGVs of artificially carious dentin after 4 weeks. However, the study of dentin remineralization by micro-CT could be impacted by the radiopacity of the restorative materials used. The relevance of this examination for the study of dentinal remineralization should be investigated.

A parametrical finite element analysis for functionally graded material overlay restoration.

The main cause of failure in bonded ceramic restorations is material fracture due to excessive stress concentration at the base of the prosthesis. The design of restorative functionally graded materials (FGM) could represent a major advance in dissipating mechanical stresses during occlusal contacts. The aim of this paper is to carry out a complete factorial design of finite element analyses to optimize a multilayer FGM introduced at the bottom of an overlay prosthesis. The number and thickness of layers vary within a spectrum compatible with ceramic shaping processes whereas Young's moduli variations are set in the range of dental tissues. For a 1.5-mm thick prosthesis, the optimal FGM configuration appears to be a 5 layers of 0.2 mm thickness with a linear distribution of Young's modulus from 30 to 70 GPa. This configuration was implemented in a 3D model of a restored tooth with realistic geometry to validate the proof-of-concept.

Retention loss and wear assessment of three attachment systems for implant retained-mandibular overdentures: An in vitro study.

BACKGROUND: The stud-shaped attachment systems (AS) with different shape designs (ball, cylindrical, conical) and materials (metallic, plastic, or a combination of both) are commonly used to provide better retention and stability in implant-retained mandibular overdentures (IRMO). PURPOSE: The purpose of the present study was to evaluate and compare the retention loss and the wear (patterns, location, material loss) of three resilient unsplinted AS: a well-established ball attachment system (BAS) and two more recent cylindrical attachment systems (CAS), Locator R-Tx® and Novaloc®. MATERIALS AND METHODS: The implants, their corresponding abutments, the color-coded or position-coded retention devices (RD), the matrix metal housing were incorporated within CAD/CAM resin blocks and cyclically loaded with 19.6 N along the implant axis in a chewing machine to simulate 10,000 insertion-removal cycles (IRC). At cycle 10, 100, 1,000, 5,000, and 10,000, the retention force was measured using a universal testing machine. The wear was qualitatively examined using a binocular magnifier for both systems, and quantitatively assessed from micro-computed tomography acquisitions for CAS. Material loss exceeding 50 µm was considered significant. RESULTS: The three AS showed different retentive behavior along time. All the Locator R-Tx® RD lost more than 50 % of their retention after 10,000 IRC. The retention of the Ball System slightly varied over time, the final retention loss in Bmed and Bmax groups being lower than 25 % of the initial retention. Wear was located at the tip of their gold RD and at the equator area of their ball abutment. For Locator R-Tx®, the more retentive the plastic RD, the greater its wear and retention loss. Only Novaloc® maintained a stable retention with even a slight tendency to increase and showed a negligible wear. Implant abutments of the CAS showed no significant wear. CONCLUSION: After 10,000 IRC, corresponding to approximately 5-years clinical use, almost all RD provided retention force over 5 N, which could be sufficient to maintain satisfaction in most of the patients. The retention loss observed most prominently for the Locator R-Tx®, then for the Ball System, seemed to correlate with the wear observed on their RD. The practitioner may expect less RD maintenance with the Novaloc® stable retention overtime.

Initial retention force of three attachment systems for implant retained-mandibular overdentures: An in vitro study.

PURPOSE: To evaluate and compare the initial retention force of three resilient unsplinted attachment systems for implant-retained mandibular overdentures: two cylindrical attachment systems (Locator R-Tx® and Novaloc®), and one ball attachment system (Ball System). MATERIALS AND METHODS: For each attachment system, initial retention is measured as the average of the maximal dislodging forces during 10 insertion-removal cycles. For the Ball System, three activation degrees of the matrix are included versus four and six color-coded retention devices for the Locator R-Tx® and the Novaloc®, respectively, to represent the complete regular retention devices panel. For each retention device or activation degree, eight samples are tested. RESULTS: The initial retention range is similar between the Ball System (7.7 ± 3.4 N - 19.9 ± 4.6 N) and the Novaloc® (2.0 ± 0.5 N - 18.9 ± 1.4 N) and broader for the Locator R-Tx® (3.3 ± 5.0 N - 60.2 ± 6.0 N). In each attachment system, the initial retention of each retention device is significantly different from the others, except for the two most retentive Novaloc® ones. Retention devices were also classified according to their initial retention (low, medium, and maximum). In each retention group, the Novaloc® and the Ball System provided similar retention values lower than the Locator R-Tx®. CONCLUSION: Most of the retention devices tested provided an initial retention force of over 5 N for all three attachment systems. The Locator R-Tx® had the most comprehensive range, and the Novaloc® seemed to provide the most reproducible values, unlike the Ball System due to the activation required by the operator.

Online large volume sample staking preconcentration and separation of enantiomeric GHRH analogs by capillary electrophoresis.

A capillary electrophoresis method is proposed to analyze the four most well-known growth hormone-releasing hormone (GHRH) analogs that are misused by athletes. Dimethyl-ß-cyclodextrin used as a chiral selector allowed, for the first time, the separation of those basic peptide analogs, including enantiopeptides (sermorelin and CJC-1293) that differ by the chirality of only one amino acid. To increase the method sensitivity, electrokinetic preconcentration methods have been investigated. The large volume sample stacking with polarity switching (PS-LVSS) method with an injected sample volume corresponding to 80% of the capillary one was found superior to the sweeping in terms of signal enhancement factor (SEF). Acid and organic solvent addition to the sample (0.1 mM phosphoric acid with 30% methanol) led to a twofold signal improvement, when compared to water as a matrix. We increased capillary dimensions to provide a signal enhancement through the injection of a larger sample volume. Finally, using a combination of the optimized PS-LVSS preconcentration with the chiral capillary zone electrophoresis (CZE), the GHRH analogs were separated and limits of detection between 75 and 200 ng/mL were reached. This method was successfully applied to urine after a desalting step. An optimized C18 SPE was used for that purpose in order to provide low sample conductivity (<130 µS/cm) and preserve the efficiency of LVSS preconcentration. SEF of 640 was obtained with desalted urine spiked with sermorelin by comparison to the CZE (without preconcentration) method.

CAR T-Cells for the Treatment of Refractory or Relapsed Large B-Cell Lymphoma: A Single-Center Retrospective Canadian Study.

BACKGROUND: Chimeric antigen receptor (CAR) T-cells are an important new third-line treatment option for large B-cell lymphoma (LBCL). The objective response rates in pivotal early phase clinical trials with CAR T-cells were very promising. The objective of this study was to describe the efficacy results obtained with CAR T-cells infusions in our institution and to compare the toxicities of our cohort with those of pivotal trials and studies conducted in a real-life setting. PATIENTS AND METHODS: Efficacy and safety data were retrospectively collected from 25 patients with LBCL treated with CAR T-cells therapy at CHU de Québec-Université Laval. A literature search was then performed to identify other efficacy or safety data from a real-life setting. RESULTS: At 3 months post infusion, the objective response rate (ORR) in our population with tisagenlecleucel and axicabtagene-ciloleucel were 20% and 47%, respectively. Bulky disease was the only negative predictor of poor response at 3 months (0% vs. 53%, P = .03). Bulky disease was associated with a median PFS of 2 months compared to 5 months for non-bulky disease (P = .0009). Grade ≥ 3 hematological toxicities were greater in patients treated with axi-cel (60% vs. 20%, P = .048), without bone marrow involvement (55% vs. 0%, P =.046), without stage IV disease (72% vs. 21%, P =.02), with refractory disease (67% vs. 10%, P =.01) or having been affected by cytokine release syndrome (58% vs. 0%, P =.02). CONCLUSION: The poor response rate at 3 months after infusion in our cohort was influenced mainly by bulky disease. Further studies are needed to better characterize the loss of efficacy of CAR T-cells because the majority of patients will relapse over time.

Evaluation of Retention, Wear, and Maintenance of Attachment Systems for Single- or Two-Implant-Retained Mandibular Overdentures: A Systematic Review.

Attachment systems (AS) enhance retention and stability by anchoring the overdentures to implants. Since 2002, the McGill consensus statement recommends the 2-implant-retained overdentures as the standard choice for edentulous mandible (2-IRMO). Considering the large number of AS available, it remains difficult for a practitioner to make a reasoned choice. A systematic review was conducted in PubMed/Medline and carried out independently by three authors, on retention, wear, and maintenance of AS used clinically or in vitro specifically for 1- or 2-IRMO. The 45 selected studies include 14 clinical and 31 in vitro studies. The risk of bias was evaluated according to the revised Cochrane risk of bias tool for randomized trials (RoB 2). The initial retention force of the cylindrical system is higher than the ball system. The retention loss, related to the wear of the retention device, is responsible for the most common need of maintenance, requiring activation or replacement. Plastic retention devices wear out faster and more significantly than metal ones, implying a worse time behavior of cylindrical systems, but their maintenance rate is similar. Neither system appears categorically superior. Cylindrical systems provide higher initial retention than ball ones; this advantage reduces over time with wear without affecting their need for maintenance.

Polylactic acid as a biocompatible polymer for three-dimensional printing of interim prosthesis: Mechanical characterization.

Mechanical properties of polylactic acid (PLA), which is a biopolymer obtained via 3D-printing, were compared with conventional resins for the realization of interim prosthesis. A PLA built by fused deposition modeling and traditional interim resins (Unifast®, Integrity®, Temporary CB®) were divided into 4 groups (n=10). Each group was investigated for Young modulus, flexural strength, microhardness and analysis of the fractured surface. Data were analyzed by Kruskal-Wallis and ANOVA (α=0.05). The porosity of the PLA was calculated from the crystallinity degree and density. PLA-group showed an elastic modulus and flexural strength in the same range than Integrity®-group, better than Unifast®-group and inferior to Temporary CB®-group (p<0.05). PLA-group microhardness was equivalent to Unifast®-group and inferior to Integrity® and Temporary CB® groups (p<0.05). Due to mechanical properties similar to conventional resins and the low porosity rate, this biocompatible 3D-printed polymer may be an interesting alternative to conventional polymer to build temporary prosthesis.

Selective Laser Melted Titanium Alloy for Transgingival Components: Influence of Surface Condition on Fibroblast Cell Behavior.

PURPOSE: To mechanically characterize and assess the biological properties of Ti6Al4V surfaces obtained by Selective Laser Melting in order to determine whether this process is conceivable for production of implant-supported prostheses and particularly trans-gingival components. As-built and polished surfaces were studied in comparison with components obtained by computer numerical control machining technology in order to consider whether the properties are in the same range as the conventional method currently used. MATERIALS AND METHODS: Cylindrical specimens of Ti6Al4V (n = 6) were built with Selective Laser Melting for the characterization of mechanical properties according to ISO 22674 and discs (n = 12) were fabricated in the same conditions for cytotoxicity evaluation. Discs (n = 12) of Ti6Al4V were also obtained by computer numerical control machining as control. Half of the number of discs (n = 6) from each process were polished, to simulate the laboratory protocol for polishing of transmucosal components and half of the discs remained unaltered (as-built). Surface roughness measurements of disc specimens (as-built and polished) were compared with computer numerical control milling specimens (as-built and polished). Proliferation of human gingival fibroblasts on Ti6Al4V surfaces was also assessed for each condition. Viability and cell morphology were then evaluated qualitatively. Ra and Sa data were compared using Student's t-test (α = 0.05) and metabolic activity data were compared using Kruskal-Wallis statistical test (α = 0.05). RESULTS: Selective Laser Melting specimens showed elongation at break greater than 2% and 0.2% yield strength better than 500MPa which complied with ISO 22674 standards. Although Selective Laser Melting samples displayed significantly increased roughness on as-built surfaces compared to computer numerically controlled milling samples (p < 0.05), no statistically significant difference was observed after mechanical polishing (p = 0.279). Regarding metabolic activity, no statistical difference was observed between groups at day 3 (p > 0.05) and fibroblasts showed a viability higher than 97% on all discs. Cell shapes on polished samples suggested moderate adhesion compared to unpolished samples. CONCLUSION: With the manufacturing parameters selected in this study, Selective Laser Melting of Ti6Al4V appeared to be compatible with a prosthetic application type 4 according to ISO 22674. Surfaces obtained, followed by recommended postprocessing provided components with equivalent biological properties compared to computer numerical control machining technology.

3D-printed protected face shields for health care workers in Covid-19 pandemic.

The coronavirus pandemic resulted in a shortage of protective equipment. To meet the request of eye-protecting devices, an interdisciplinary consortium involving practitioners, researchers, engineers and technicians developed and manufactured thousands of inexpensive 3D-printed face shields, inside hospital setting. This action leads to the concept of "concurrent, agile, and rapid engineering".

Development of Enthesopathies and Joint Structural Damage in a Murine Model of X-Linked Hypophosphatemia.

X-linked hypophosphatemia (XLH) is characterized by rickets and osteomalacia, caused by inactivating mutations in the Phosphate-regulating endopeptidase homolog X-linked (PHEX) gene. With aging, adult patients develop paradoxical heterotopic calcifications of tendons and ligaments at their insertion sites (enthesophytes), and joint alterations. Understanding the progression of this structural damage that severely affects patients' quality of life will help to improve the management of XLH. Here, we characterized the occurrence of enthesophytes and joint alterations through a 12 month in vivo micro-CT follow-up in the Hyp mouse, a murine model of XLH (n = 5 mice per group). Similar to adult patients with XLH, Hyp mice developed calcaneal enthesophytes, hip joint alterations, erosions of the sacroiliac joints and periarticular calcifications. These lesions were already present at month 3 and gradually worsened over time. In sharp contrast, no abnormalities were observed in control mice at early time points. Histological analyses confirmed the presence of bone erosions, calcifications and expansion of mineralizing enthesis fibrocartilage in Hyp mice and their absence in controls and suggested that new bone formation is driven by altered mechanical strain. Interestingly, despite a strong deformation of the curvature, none of the Hyp mice displayed enthesophyte at the spine. Peripheral enthesophytes and joint alterations develop at the early stages of the disease and gradually worsen overtime. Overall, our findings highlight the relevance of this preclinical model to test new therapies aiming to prevent bone and joint complications in XLH.

Peptide enrichment by ion-pair solid-phase extraction.

The technique of Solid-Phase Extraction (SPE) is widely used in various fields to concentrate samples and the search for tools to improve recoveries remains of outmost importance. The use of polymer based cartridges has become prevailing in a broad range of fields to enrich peptides from biological matrices. However, the existing SPE protocols are characterized by disparity. Ion-pairing (IP) reagents are commonly used in chromatographic applications, but their combination with SPE is less known. The aim of this study was to evaluate various SPE loading conditions, including the use of IP reagents, to improve the recoveries of nine selected peptide molecules. Control of pH and the use of IP reagents were found to be crucial to improve the enrichment of the peptides, especially cationic peptides, for which an up to ten-fold increase was observed. The practical potential of the presented theoretical findings were verified by employing IP-SPE for the development of an efficient extraction method for the doping relevant peptide Synacthen. The general proof of principle was obtained by analysis of excretion study urine samples and validation was performed with focus on the limit of detection (20 pg/ml) and recovery (37%).

Mechanical Properties of CAD/CAM Denture Base Resins.

PURPOSE: To evaluate the influence of fabrication processes on the mechanical properties of denture base resins. MATERIALS AND METHODS: Flexural strength, fracture toughness, and Vickers hardness were measured on a conventional pack-and-press resin (PRO), a resin for injection molding (CAP), and a CAD/CAM disc (CAD). RESULTS: For maximal flexural strength, PRO (97.31 MPa) was stronger than CAD (87.98 MPa) and CAP (79.35 MPa). CAD displayed hardness similar to PRO and high fracture toughness. CONCLUSION: CAD/CAM denture base resin mechanical properties result from the evolution of denture base materials, combining high-impact fracture toughness and improved flexural strength and hardness.

Can repeated in vivo micro-CT irradiation during adolescence alter bone microstructure, histomorphometry and longitudinal growth in a rodent model?

In vivo micro-computed tomography (micro-CT) can monitor longitudinal changes in bone mass and microstructure in small rodents but imposing high doses of radiation can damage the bone tissue. However, the effect of weekly micro-CT scanning during the adolescence on bone growth and architecture is still unknown. The right proximal tibia of male Sprague-Dawley rats randomized into three dose groups of 0.83, 1.65 and 2.47 Gy (n = 11/group) were CT scanned at weekly intervals from 4th to 12th week of age. The left tibia was used as a control and scanned only at the last time point. Bone marrow cells were investigated, bone growth rates and histomorphometric analyses were performed, and bone structural parameters were determined for both left and right tibiae. Radiation doses of 1.65 and 2.47 Gy affected bone marrow cells, heights of the proliferative and hypertrophic zones, and bone growth rates in the irradiated tibiae. For the 1.65 Gy group, irradiated tibiae resulted in lower BMD, Tb.Th, Tb.N and a higher Tb.Sp compared with the control tibiae. A decrease in BMD, BV/TV, Tb.Th, Tb.N and an increase in Tb.Sp were observed between the irradiated and control tibiae for the 2.47 Gy group. For cortical bone parameters, no effects were noticed for 1.65 and 0.83 Gy groups, but a lower Ct.Th was observed for 2.47 Gy group. Tibial bone development was adversely impacted and trabecular bone, together with bone marrow cells, were negatively affected by the 1.65 and 2.47 Gy radiation doses. Cortical bone microstructure was affected for 2.47 Gy group. However, bone development and morphometry were not affected for 0.83 Gy group. These findings can be used as a proof of concept for using the reasonable high-quality image acquisition under 0.83 Gy radiation doses during the adolescent period of rats without interfering with the bone development process.

Comparison of Mechanical Properties of CAD/CAM-Milled and Selective Laser-Melted Ti-6Al-4V for Dental Superstructures.

PURPOSE: To determine whether selective laser melting (SLM) is suitable for the fabrication of dental superstructures. MATERIALS AND METHODS: Mechanical properties of Ti-6Al-4V, manufactured with SLM or numerically controlled milling, were evaluated and compared. RESULTS AND CONCLUSION: Both groups showed a mechanical strength greater than 500 MPa and an elongation greater than 2%, as required by the International Organization for Standardization 22674 standard. However, a reduced ductility was observed for SLM samples.

Simultaneous microstructural and mechanical characterization of human corneas at increasing pressure.

The cornea, through its shape, is the main contributor to the eye׳s focusing power. Pathological alterations of the cornea strongly affect the eye power. To improve treatments, complex biomechanical models have been developed based on the architecture and mechanical properties of the collagen network in the stroma, the main layer of the cornea. However, direct investigations of the structure of the stroma, as well as its link to the mechanical response, remained limited. We propose here an original set up, associating nonlinear optical imaging and mechanical testing. By using polarization resolved Second Harmonic signals, we simultaneously quantified micrometer (orientation of the collagen lamellae) and nanometer (local disorder within lamellae) scale corneal organization. We showed that the organization of the lamellae changes along the stroma thickness. Then, we measured simultaneously the deformation on the epithelial side of the cornea and the reorientation of the collagen lamellae for increasing intraocular pressure levels, from physiological ones to pathological ones. We showed that the observed deformation is not correlated to initial orientation, but to the reorganization of the lamellae in the stroma. Our results, by providing a direct multi-scale observation, will be useful for the development of more accurate biomechanical models.

3D analysis from micro-MRI during in situ compression on cancellous bone.

A mini-compression jig was built to perform in situ tests on bovine trabecular bone monitored by micro-MRI. The MRI antenna provided an isotropic resolution of 78 microm that allows for a volume correlation method to be used. Three-dimensional displacement fields are then evaluated within the bone sample during the compression test. The performances of the correlation method are evaluated and discussed to validate the technique on trabecular bone. By considering correlation residuals and estimates of acquisition noise, the measured results are shown to be trustworthy. By analyzing average strain levels for different interrogation volumes along the loading direction, it is shown that the sample size is less than that of a representative volume element. This study shows the feasibility of the 3D-displacement and strain field analyses from micro-MRI images. Other biological tissues could be considered in future work.