Cement opacity and color as influencing factors on the final shade of metal-free ceramic restorations.

OBJECTIVE: To investigate the influence of opacity and color of luting cements on the final shade of metal-free restorations. MATERIALS AND METHODS: Five resin cement colors in combination with four different thicknesses of CAD/CAM ceramic materials were tested, and a composite substrate was used as dentin color reference (n = 3). Specimen color was measured with a spectrophotometer equipped with an integrating sphere before and after cementation (CIELAB). Cement and ceramic color and opacity (TP) were assessed by measuring the tested ceramic thickness as a 1-mm thick disk for each of the cement shades. The differences in color were evaluated (ΔE00 ). Data were statistically analyzed by a Two-Way ANOVA followed by the Tukey Test for post-hoc comparison (P < .05) and multiple comparison Pearson's test (P < .05); the acceptability and perceptibility threshold were evaluated. RESULTS: Statistically significant influence was found for factors ceramic thickness and cement shade (P < .001). Perceptible and unacceptable color changes were induced on the final restoration by resin cements (ranging from ΔE00  = 0.69 ± 0.54 to ΔE00  = 5.53 ± 0.46), the correlation between factors became strong (r2 > 0.6) in case of mismatch between color and translucency of cement and ceramic. Only the clear shade in combination with the thickest ceramic, resulted in an imperceptible color change (ΔE00  = 0.69 ± 0.54). CONCLUSIONS: The final shade of ceramic restorations can be influenced by resin cements; the magnitude of influence is related to the cement optical properties. CLINICAL SIGNIFICANCE: In order to influence the final shade of a ceramic restoration, a cement more opaque than the restorative material should be used. Conversely, in the case of a fitting shade of the restoration, a cement more translucent than the restoration should be used to avoid undesired changes.

The SARS-CoV-2 Spike protein disrupts human cardiac pericytes function through CD147 receptor-mediated signalling: a potential non-infective mechanism of COVID-19 microvascular disease.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes a broad range of clinical responses including prominent microvascular damage. The capacity of SARS-CoV-2 to infect vascular cells is still debated. Additionally, the SARS-CoV-2 Spike (S) protein may act as a ligand to induce non-infective cellular stress. We tested this hypothesis in pericytes (PCs), which are reportedly reduced in the heart of patients with severe coronavirus disease-2019 (COVID-19). Here we newly show that the in vitro exposure of primary human cardiac PCs to the SARS-CoV-2 wildtype strain or the α and δ variants caused rare infection events. Exposure to the recombinant S protein alone elicited signalling and functional alterations, including: (1) increased migration, (2) reduced ability to support endothelial cell (EC) network formation on Matrigel, (3) secretion of pro-inflammatory molecules typically involved in the cytokine storm, and (4) production of pro-apoptotic factors causing EC death. Next, adopting a blocking strategy against the S protein receptors angiotensin-converting enzyme 2 (ACE2) and CD147, we discovered that the S protein stimulates the phosphorylation/activation of the extracellular signal-regulated kinase 1/2 (ERK1/2) through the CD147 receptor, but not ACE2, in PCs. The neutralisation of CD147, either using a blocking antibody or mRNA silencing, reduced ERK1/2 activation, and rescued PC function in the presence of the S protein. Immunoreactive S protein was detected in the peripheral blood of infected patients. In conclusion, our findings suggest that the S protein may prompt PC dysfunction, potentially contributing to microvascular injury. This mechanism may have clinical and therapeutic implications.

Flexural resistance of CAD-CAM blocks. Part 3: Polymer-based restorative materials for permanent restorations.

PURPOSE: Concurrently with the growing interest in CAD-CAM systems, several new materials of different chemical nature have become available. As an alternative to ceramics, numerous polymer-based materials have recently been proposed for permanent prosthetic restorations. Aim of this study was to test the CAD-CAM polymer-based materials available on the market, comparing mean flexural strength, Weibull characteristic strength and Weibull modulus. METHODS: Seven types of polymer-based blocks were tested: Lava Ultimate, 3M; Brilliant Crios, Coltene; Cerasmart, GC; Block HC, Shofu; Katana Avencia, Noritake; Grandio Blocs, Voco; Tetric CAD, and Ivoclar-Vivadent. Specimens were cut out from blocks, finished, polished, and tested in a three-point bending test apparatus until failure (n=30). Flexural strength, Weibull characteristic strength, and Weibull modulus were calculated. Flexural strength data were statistically analyzed. ANOVA on Ranks was applied, followed by the Dunn's test for post hoc comparisons (P= 0.05). RESULTS: Flexural strength values (MPa) were measured (mean±standard deviation). Different letters in parentheses label statistically significant differences: Grandio Blocs 266±24(a), Brilliant Crios 259±21(ab); Tetric CAD 254±15(ab); Katana Avencia 241±29(bc); Cerasmart 221±24(cd); Lava Ultimate 196±23(de); Block HC 139±10(e). All the tested materials had flexural strengths greater than 100 MPa, thereby satisfying the requirements of ISO standards for polymer-based materials. For all the tested materials the Weibull characteristic strength was greater than 100 MPa. Weibull modulus ranged between 21.20 (Tetric CAD) and 9.09 (Katana Avencia). CLINICAL SIGNIFICANCE: Even though all the CAD-CAM polymer-based materials marketed in blocks tested in the present study satisfy the requirements of ISO standard for polymer-based materials, their flexural resistance differs significantly. The data presented in the study may be helpful to clinicians for selecting the most appropriate materials for each clinical case.

Performance of CAD/CAM fabricated fiber posts in oval-shaped root canals: An in vitro study.

PURPOSE: To assess the push-out strength, the cement layer thickness and the interfacial nanoleakage of prefabricated fiber posts, CAD/CAM fiber posts and metal cast posts cemented into oval-shaped root canals. METHODS: Oval-shaped post spaces were prepared in 30 single-rooted premolars. Roots were randomly assigned to three groups (n=10), according to the post type to be inserted: Group 1: Prefabricated fiber post (D.T. Light-Post X-RO Illusion); Group 2: Cast metal post; Group 3: CAD/CAM-fabricated fiber post (experimental fiber blocks). In Group 3, post spaces were sprayed with scan powder (VITA), scanned with an inEos 4.2 scanner, and fiber posts were milled using an inLab MC XL CAD/CAM milling unit. All posts were cemented using Gradia Core dual-cure resin cement in combination with Gradia core self-etching bond (GC). After 24 hours, the specimens were sectioned perpendicular to the long axis into six 1 mm-thick sections, which were differentiated by the root level. Sections from six roots per group were used to measure the cement thickness and subsequently for the thin-slice push-out test, whereas the sections from the remaining four teeth were assigned to interfacial nanoleakage test. The cement thickness around the posts was measured in micrometers (µm) on the digital images acquired with a digital microscope using the Digimizer software. Thin-slice push-out test was conducted using a universal testing machine at the crosshead speed of 0.5 mm/minute and the bond strength was expressed in megaPascals (MPa). The interfacial nanoleakage was observed under light microscope and quantified by scoring the depth of silver nitrate penetration along the post-cement-dentin interfaces. The obtained results were statistically analyzed by Kruskal-Wallis ANOVA, followed by the Dunn's Multiple Range test for post hoc comparisons. The level of significance was set at P< 0.05. RESULTS: Statistically significant differences were found among the groups in push-out bond strength, cement thickness and interfacial nanoleakage (P< 0.05). CAD/CAM-fabricated fiber posts achieved retention that was comparable to that of cast metal posts and significantly higher than that of prefabricated fiber posts. The cement layer thickness around CAD/CAM-fabricated fiber posts was significantly lower than around prefabricated fiber posts, but higher than that around cast metal posts. Root level was not a significant factor for push-out strength in any of the groups, whereas it significantly affected cement layer thickness only in the prefabricated fiber post group. No differences were observed in interfacial nanoleakage between CAD/CAM fabricated and prefabricated fiber posts, while nanoleakage recorded in cast metal posts was significantly lower. CLINICAL SIGNIFICANCE: CAD/CAM fabricated fiber posts could represent a valid alternative to traditionally used posts in the restoration of endodontically-treated teeth with oval or wide root canals, offering the advantages of better esthetics, retention, and cement thickness values that are comparable to cast post and cores.

Vascular stem cells-potential for clinical application.

INTRODUCTION: Cell therapy is a growing area of research as an alternative to pharmaceuticals or surgery for the treatment of ischaemic disease. Studies are focusing on delivering tissue-derived cells into damaged organs to promote vascular regeneration or gain of function. SOURCES OF DATA: Pubmed, clinicaltrials.gov, BHF website. AREAS OF AGREEMENT: Stem cells have the potential to become a viable treatment for many diseases, as indicated by the numerous pre-clinical studies demonstrating therapeutic benefit. AREAS OF CONTROVERSY: The mechanisms of action for transplanted stem cells are still open to debate. Proposed mechanism includes direct cell incorporation and paracrine action. Additionally, the secretome produced by transplanted cells remains largely unknown. GROWING POINTS: Initial studies focused on delivering stem cells by injection; however, current research is utilizing biomaterials to target cell delivery to specific areas. AREAS TIMELY FOR DEVELOPING RESEARCH: Whilst stem cell research in the laboratory is expanding rapidly, transition into clinical studies is hindered by the availability of equivalent clinical grade reagents.

Comparison of Contrast Ratio, Translucency Parameter, and Flexural Strength of Traditional and "Augmented Translucency" Zirconia for CEREC CAD/CAM System.

PURPOSE: Tetragonal zirconia polycrystals (TZP) can be used via CAD/CAM technique as metal replacement for fixed partial dentures. However, its intense white color and high opacity may represent an aesthetic limit. New TZPs with a claimed higher degree of translucency were recently marketed. The aim of the study was to investigate contrast ratio (CR), translucency parameter (TP), flexural strength (σ), Weibull characteristic strength (σ0 ), and Weibull modulus (m) of three "traditional" (IPS e.max Zir-CAD, inCoris ZI, VITA In-Ceram YZ) and two "increased translucency" (inCoris TZI, VITA In-Ceram YZ HT) Y-TZPs. METHODS: For flexural strength, ISO 6872:2008 was followed. Bars (N = 40) were cut from pre-sintered blocks. Dense-sintering, finishing, and polishing were performed in order to obtain specimens of 15 × 4 × 1.2 mm. Samples were tested with three-point bending setup in a universal testing machine. For CR and TP, specimens (N = 10) were cut perpendicularly to the long axis from pre-sintered blocks. After the dense-sintering, specimens were finished and polished in order to obtain tiles of 12 × 15 × 1 mm. CR and TP were measured with a spectrophotometer equipped with an integrating sphere. RESULTS: No significant difference was found regarding flexural strength. A significant difference was found both for CR and TP among tested groups. VITA In-Ceram YZ HT and inCoris TZI showed the higher translucency. The difference was not statistically significant when compared with VITA In-Ceram YZ, and statistically significant when compared with IPS e.max Zir-CAD and inCoris ZI. CONCLUSION: The new "augmented translucency" TZPs showed higher translucency and similar flexural strength than "traditional" TZPs. CLINICAL SIGNIFICANCE: Monolithic zirconia use is partially restricted due to the zirconia low translucency. The new "augmented translucency" zirconia showed a modest but perceptible increase in translucency and a similar flexural resistance, thus increasing the clinically suitable thickness range with optimized aesthetic and resistance. (J Esthet RestorDent 28:S32-S39, 2016).

Influence of luting agent translucency on fiber post retention.

The aim was to assess the influence of cement translucency on the retentive strength of luted fiber posts. Twenty extracted human premolars were randomly divided into four equal groups, based on the combinations of materials to be tested. Two post types of the same size, shape, and chemical composition, but different light-transmission properties [Translucent post (TP) and Opaque post (OP)] were selected. The two post types were luted using the etch-and-rinse, light-curing adhesive in combination with two shades of the same resin cement of markedly different light-transmitting ability [Transparent shade (TS) and Opaque shade (OS)]. Early post retention was assessed using the thin-slice push-out test. Post type did not significantly influence post retention; however, cement translucency emerged as a relevant factor in intraradicular cementation, with the TS achieving higher push-out strengths. The between-factor interaction was also statistically significant; specifically, OP-OS yielded significantly lower retentive strengths than all the other groups. Post translucency did not influence post retention, provided that a highly translucent cement was utilized for luting.

Influence of coloring procedure on flexural resistance of zirconia blocks.

STATEMENT OF PROBLEM: The white color of zirconia limits the possibility of a natural-looking restoration. Industrially precolored blocks and green-stage coloring liquids are used to obtain shaded zirconia. Several authors have reported that pigments may negatively affect the mechanical characteristics of the material. PURPOSE: The purpose of this in vitro study was to investigate the effect of a recently marketed coloring system on the flexural strength (σ), Weibull characteristic strength (σ0), and Weibull modulus (m) of a zirconia for computer-aided design/computer-aided manufacturing (CAD/CAM) systems. MATERIAL AND METHODS: Noncolored white blocks (In-Ceram YZ), industrially precolored blocks (In-Ceram YZ col. LL1p), and green-stage infiltration-shaded blocks in 4 colors (In-Ceram YZ Coloring Liquids) were tested. Industrially precolored specimens (n = 30) were assigned to the PREC group. Noncolored specimens were divided into 5 groups (n = 30). Group CNTR was not treated (control). Groups INF-N, INF-L, INF-M, and INF-I were subject to green-stage infiltration (neutral, light, medium, and intense, respectively). Specimens were tested in a 3-point bending apparatus following ISO 6872:2008 specifications. Data were analyzed by 1-way ANOVA. RESULTS: The calculated flexural strengths (MPa) were CNTR 1232.56 ± 103.91; PREC 1215.16 ± 141.42; INF-N 1280.72 ± 160.10; INF-L 1218.92 ± 78.63; INF-M 1153.71 ± 176.80; and INF-I 1248.46 ± 111.73. No statistically significant differences were found among the tested groups (P = .195). CONCLUSIONS: Unlike what has been reported for other combinations of zirconia and coloring liquids, the coloring technique tested in the present study did not negatively influence the flexural characteristics of the tested zirconia.

Translucency of ceramic materials for CEREC CAD/CAM system.

OBJECTIVES: To compare translucency of the ceramic materials (CEREC CAD/CAM). MATERIALS AND METHODS: Fifteen ceramic materials for CEREC CAD/CAM system were evaluated: IPS e.max HT/LT/MO, ZirCAD, Empress HT/LT; VITA Mark II, VITA AL; VITA YZ, VITA In-Ceram Spinell/Alumina/Zirconia; and Sirona InCoris AL; Sirona InCoris ZI/TZI. Specimens (0.5-mm and 1.0-mm thick; n = 10 each material) were cut from commercial blocks using a water-cooled diamond saw. Contrast ratio (CR = YB /YW ) was measured using a spectrophotometer with an integrating sphere. Kruskal-Wallis one way analysis of variance was performed followed by Dunn's multiple test for post-hoc. RESULTS: CR varied from 0.35 to 1.00 and from 0.48 to 1.00 for 0.5 mm and 1.0 mm thicknesses, respectively. CR increased in the following order: IPS e.max HT (most translucent-least opaque), IPS Empress HT, VITA Mark II, IPS Empress LT, IPS e.max LT, In-Ceram Spinell, IPS e.max MO, VITA YZ, InCoris TZI, IPS e.max ZirCAD, InCoris ZI, In-Ceram Alumina, VITA AL, InCoris AL, and In-Ceram Zirconia (least translucent-most opaque). CONCLUSIONS: The null hypothesis has been rejected because tested materials exhibited a wide range of CR. Translucency needs to be taken into account in different clinical situations, including considerations associated with thickness of restoration and/or particular layers. CLINICAL SIGNIFICANCE: A wide range of translucency was identified for the ceramic materials tested. This variability has to be taken into account for the selection of the materials in different clinical situations also related to the thickness clinically required.

Protocol to decellularize porcine right ventricular outflow tracts using a 3D printed flow chamber.

Surgical treatment of pediatric congenital heart disease with tissue grafts is a lifesaving intervention. Decellularization to reduce immunogenicity of tissue grafts is an increasingly popular alternative to glutaraldehyde fixation. Here, we present a protocol to decellularize porcine right ventricular outflow tracts using a 3D printed flow chamber. We describe steps for 3D printing the flow rig, preparing porcine tissue, and using the flow rig to utilize shear forces for decellularization. We then detail procedures for characterizing the acellular scaffold. For complete details on the use and execution of this protocol, please refer to Vafaee et al.1.

Microleakage of Class II restorations and microtensile bond strength to dentin of low-shrinkage composites.

PURPOSE: To evaluate the microleakage of Class II cavities restored with experimental low-shrinking resin composites proposed for bulk filling and to measure their microtensile bond strength (microTBS) to dentin and compare to those of previously marketed low-shrinkage composites. METHODS: Class II cavities (7 mm occluso-gingival height, 2 mm mesio-distal depth of the box, 4 mm occlusal depth, 4 mm bucco-lingual width) were prepared in 50 molars and randomly divided into five groups (n = 10), according to the material: SureFil SDR flow (SDR), Filtek Silorane (FS) and experimental materials (G-aenial Flo bulk fill, GF; G-aenial Universal Flo bulk fill, GUF; GC Kalore bulk fill, GK). Microleakage was separately assessed at enamel and dentin margins by scoring the depth of silver-nitrate penetration. Twenty teeth divided into five groups (n = 4) were selected for microTBS testing. The same materials as for microleakage assessment were placed in bulk to mid-coronal dentin. Microtensile beams were loaded in tension, and microTBS at failure was calculated in MPa. Microleakage and microTBS data were analyzed by ANOVA on ranks, followed Dunn's post hoc test (P< 0.05). RESULTS: Microleakage was not observed at the enamel interface in any of the groups. At the dentin interface, SDR recorded significantly higher microleakage than the other materials. microTBS of GF, GUF and GK did not differ among each other (33 +/- 12 MPa, 31 +/- 11 MPa, 30 +/- 9 MPa, respectively), while SDR (63 +/- 17 MPa) and FS (55 +/- 17MPa) achieved significantly higher microTBS values. No direct association between the sealing properties and the bond strength values was observed.

Influence of Thickness of Opaque Porcelain and Alloy Color on the Final Color of Porcelain-Fused-to-Metal Restorations.

Despite the advent of metal-free solutions, porcelain-fused-to-metal restorations (PFM) are still widely used. Particularly for the latest ceramic systems, scarce information is present in the scientific literature about the ideal opaque layer thickness and the alloy color impact to achieve the desired final color of PFM restorations. This study aimed to evaluate the influence of opaque thickness variation layered on different metal alloys on the final color of PFM restorations. Opaque porcelain of one metal−ceramic system (VITA VM13) was layered in four different thicknesses (0.10 mm, 0.15 mm, 0.20 mm, and 0.25 mm) on three differently colored dental alloys: a gold−platinum alloy (yellowish), a gold−palladium alloy (light grayish), and a nickel−chromium alloy (dark grayish). The veneering porcelain layered over the opaque was kept constant (Base Dentine 0.45 mm, Transpa Dentine 0.50 mm, and Enamel 0.20 mm). Sixty specimens were fabricated, five samples for each combination of alloy/opaque thickness. The color difference (ΔE) between specimen and reference was measured using a clinical spectrophotometer. The two-way ANOVA revealed that the thickness of both the opaque (p < 0.001) and the metal alloy (p < 0.001) significantly influenced the ΔE values. Gray-colored alloys covered by a 0.10 mm thick opaque layer enabled the closest color match, whereas this occurred for yellow-color alloys covered by a 0.15 mm thick opaque layer. In contrast, the samples covered by a 0.25 mm thick opaque layer obtained the worst ΔE.

Biological Scaffolds for Congenital Heart Disease.

Congenital heart disease (CHD) is the most predominant birth defect and can require several invasive surgeries throughout childhood. The absence of materials with growth and remodelling potential is a limitation of currently used prosthetics in cardiovascular surgery, as well as their susceptibility to calcification. The field of tissue engineering has emerged as a regenerative medicine approach aiming to develop durable scaffolds possessing the ability to grow and remodel upon implantation into the defective hearts of babies and children with CHD. Though tissue engineering has produced several synthetic scaffolds, most of them failed to be successfully translated in this life-endangering clinical scenario, and currently, biological scaffolds are the most extensively used. This review aims to thoroughly summarise the existing biological scaffolds for the treatment of paediatric CHD, categorised as homografts and xenografts, and present the preclinical and clinical studies. Fixation as well as techniques of decellularisation will be reported, highlighting the importance of these approaches for the successful implantation of biological scaffolds that avoid prosthetic rejection. Additionally, cardiac scaffolds for paediatric CHD can be implanted as acellular prostheses, or recellularised before implantation, and cellularisation techniques will be extensively discussed.

The Role of Immersive Virtual Reality and Augmented Reality in Medical Communication: A Scoping Review.

Communication between clinicians and patients and communication within clinical teams is widely recognized as a tool through which improved patient outcomes can be achieved. As emerging technologies, there is a notable lack of commentary on the role of immersive virtual reality (VR) and augmented reality (AR) in enhancing medical communication. This scoping review aims to map the current landscape of literature on this topic and highlights gaps in the evidence to inform future endeavors. A comprehensive search strategy was conducted across 3 databases (PubMed, Web of Science, and Embase), yielding 1000 articles, of which 623 were individually screened for relevance. Ultimately, 22 articles were selected for inclusion and review. Similarities across the cohort of studies included small sample sizes, observational study design, use of questionnaires, and more VR studies than AR. The majority of studies found these technologies to improve medical communication, although user tolerability limitations were identified. More studies are required, presenting more robust findings, in order to draw more definitive conclusions and stronger recommendations for use of immersive VR/AR in clinical environments.

Extent of cement polymerization along dowel space as a function of the interaction between adhesive and cement in fiber post cementation.

PURPOSE: To assess whether the polymerization extent of cement is influenced by curing mode of the adhesive and/or by photoactivation of the cement. MATERIALS AND METHODS: One hundred five root segments were prepared from endodontically treated teeth. After post space preparation, the root segments were randomly divided into 7 groups, based on the cementation procedure to lute RelyX Fiber Posts (3M ESPE): 1. Variolink II (V, Ivoclar Vivadent); 2. V light-cured (LC); 3. Excite LC (ELC, Ivoclar Vivadent)/V; 4. ELC/V LC; 5. ELC-V LC (One Shot); 6. Excite DSC (EDSC)/V; 7. EDSC-V LC (One Shot). Each root segment was submitted to the acetone shake test to remove the unpolymerized resin and then cut longitudinally. On each half, the extent of cure of the cement was measured with image analysis software. RESULTS: The deepest and basically complete polymerization was obtained with EDSC (groups 6 and 7), regardless of whether light curing was performed. The extent of polymerization was most limited when adhesive was not applied (groups 1 and 2), or when ELC was only light cured, while V was allowed to auto-cure (group 3). With the one-shot polymerization of ELC and V (group 5), the extent of polymerization was similar to the procedure involving separate irradiation of adhesive and cement (group 4). The one-shot technique was significantly more effective if EDSC was used (group 6). CONCLUSION: The use of a self-activating dual-curing adhesive system in combination with a dual-curing cement enables effective luting of FRC posts regardless of the amount of light transmitted through the post.

Spectrophotometric evaluation of color match of three different porcelain systems for all-ceramic zirconia-based restorations.

PURPOSE: To determine by a spectrophotometric analysis the variations in color between the intended and the fabricated shades of three different porcelain systems when applied in a standardized thickness on a zirconia core. METHODS: Three porcelain systems for zirconia based restorations, Ivoclar IPS e.max Ceram, VITA VM9, and Creation Zi-F were tested. Nine disc-shaped (15 mm diameter, 0.5 mm thickness) specimens of VITA YZ zirconia core per group were made comprising a total of 27 discs. Three different shades (A2, A3, A4) of the Vitapan Classical shade guide were investigated. The porcelain veneer total thickness was set at 1.0 mm in all groups. The porcelain stratification was made by applying calibrated layers of porcelain. Thicknesses of single porcelain layers were calculated from drawings retrieved from the manufacturers' instructions. Color parameters (L*, a*, b*) of veneered specimens were measured by a clinical spectrophotometer. Color differences (deltaE) were calculated using a color difference formula. Two-way ANOVA and Tukey's test were used to analyze the data. RESULTS: The mean color differences for the three ceramic systems, Ivoclar IPS e.max Ceram, VITA VM9 and Creation Zi-F were respectively 4.1, 2.7 and 3.2, regardless of the shades. VITA VM9 resulted in the best average shade matching among the porcelain systems, even if results with shade A3 were considerably worse than shades with A2 and A4 (P<0.05). Color matching appeared not to be shade dependent (P>0.05) among the tested shades.

Recent Advances in KEAP1/NRF2-Targeting Strategies by Phytochemical Antioxidants, Nanoparticles, and Biocompatible Scaffolds for the Treatment of Diabetic Cardiovascular Complications.

Significance: Modulation of nuclear factor (erythroid-derived 2)-like 2 (Nrf2)-mediated antioxidant response is a key aspect in the onset of diabetes-related cardiovascular complications. With this review, we provide an overview of the recent advances made in the development of Nrf2-targeting strategies for the treatment of diabetes, with particular attention toward the activation of Nrf2 by natural antioxidant compounds, nanoparticles, and oxidative stress-modulating biocompatible scaffolds. Recent Advances: In the past 30 years, studies addressing the use of antioxidant therapies to treat diabetes have grown exponentially, showing promising but yet inconclusive results. Animal studies and clinical trials on the Nrf2 pathway have shown promising results, suggesting that its activation can delay or reverse some of the cardiovascular impairments in diabetes. Critical Issues: Hyperglycemia- and oscillating glucose levels-induced reactive oxygen species (ROS) accumulation is progressively emerging as a central factor in the onset and progression of diabetes-related cardiovascular complications, including endothelial dysfunction, retinopathy, heart failure, stroke, critical limb ischemia, ulcers, and delayed wound healing. In this context, accumulating evidence suggests a central role for Nrf2-mediated antioxidant response, one of the most studied cellular defensive mechanisms against ROS accumulation. Future Directions: Innovative approaches such as tissue engineering and nanotechnology are converging toward targeting oxidative stress in diabetes. Antioxid. Redox Signal. 36, 707-728.

Cardiac pericyte reprogramming by MEK inhibition promotes arteriologenesis and angiogenesis of the ischemic heart.

Pericytes (PCs) are abundant yet remain the most enigmatic and ill-defined cell population in the heart. Here, we investigated whether PCs can be reprogrammed to aid neovascularization. Primary PCs from human and mouse hearts acquired cytoskeletal proteins typical of vascular smooth muscle cells (VSMCs) upon exclusion of EGF/bFGF, which signal through ERK1/2, or upon exposure to the MEK inhibitor PD0325901. Differentiated PCs became more proangiogenic, more responsive to vasoactive agents, and insensitive to chemoattractants. RNA sequencing revealed transcripts marking the PD0325901-induced transition into proangiogenic, stationary VSMC-like cells, including the unique expression of 2 angiogenesis-related markers, aquaporin 1 (AQP1) and cellular retinoic acid-binding protein 2 (CRABP2), which were further verified at the protein level. This enabled us to trace PCs during in vivo studies. In mice, implantation of Matrigel plugs containing human PCs plus PD0325901 promoted the formation of αSMA+ neovessels compared with PC only. Two-week oral administration of PD0325901 to mice increased the heart arteriolar density, total vascular area, arteriole coverage by PDGFRß+AQP1+CRABP2+ PCs, and myocardial perfusion. Short-duration PD0325901 treatment of mice after myocardial infarction enhanced the peri-infarct vascularization, reduced the scar, and improved systolic function. In conclusion, myocardial PCs have intrinsic plasticity that can be pharmacologically modulated to promote reparative vascularization of the ischemic heart.

Comparison between Hydrofluoric Acid and Single-Component Primer as Conditioners on Resin Cement Adhesion to Lithium Silicate and Lithium Disilicate Glass Ceramics.

This study aimed at evaluating the effects of different surface conditionings on the microshear bond strength (µSBS) of a self-adhesive resin cement to VITA Suprinity (ZLS) and IPS e.max CAD (LD). Three surface conditioning protocols were performed on ZLS and LD before luting with a self-adhesive resin cement (RelyX Unicem 2, RXU): hydrofluoric acid (HF), HF + silane (HF + S), or Monobond Etch & Prime (EP). In each group, 15 cylindrical buildups of RXU were prepared on five milled bars and submitted to a µSBS test. Data were statistically analyzed with two-way ANOVA and Tukey's post hoc test (p < 0.05). Failure modes were recorded and classified as adhesive, mixed, cohesive in resin, or ceramic, and statistically analyzed with Fisher's exact test (p = 0.05). One additional bar per group was used for the morphological characterization of the conditioned surface by means of SEM. The material per se did not significantly influence adhesion (p = 0.744). Conditioning protocol was a significant factor: EP yielded significantly higher µSBS than HF (p = 0.005), while no significant differences emerged between EP and HF + S (p = 0.107), or HF + S and HF (p = 0.387). The material-conditioning protocol interaction was not statistically significant (p = 0.109). Significant intergroup differences were found in distribution of failure modes: mixed failures were predominant in the ZLS/EP group, while the other groups showed a prevalence of adhesive failures. The self-etching primer showed promising results in terms of immediate bond strength of a self-adhesive resin cement to lithium-silica-based glass ceramics, suggesting its alternative use to hydrofluoric acid and silane conditioning protocols.

Three-Dimensional Printable Enzymatically Active Plastics.

Here, we describe a facile route to the synthesis of enzymatically active highly fabricable plastics, where the enzyme is an intrinsic component of the material. This is facilitated by the formation of an electrostatically stabilized enzyme-polymer surfactant nanoconstruct, which, after lyophilization and melting, affords stable macromolecular dispersions in a wide range of organic solvents. A selection of plastics can then be co-dissolved in the dispersions, which provides a route to bespoke 3D enzyme plastic nanocomposite structures using a wide range of fabrication techniques, including melt electrowriting, casting, and piston-driven 3D printing. The resulting constructs comprising active phosphotriesterase (arPTE) readily detoxify organophosphates with persistent activity over repeated cycles and for long time periods. Moreover, we show that the protein guest molecules, such as arPTE or sfGFP, increase the compressive Young's modulus of the plastics and that the identity of the biomolecule influences the nanomorphology and mechanical properties of the resulting materials. Overall, we demonstrate that these biologically active nanocomposite plastics are compatible with state-of-the-art 3D fabrication techniques and that the methodology could be readily applied to produce robust and on-demand smart nanomaterial structures.