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Patricia Maria Wiziack Zago,1 Ilza Maria Oliveira Sousa,2 Leila Servat-Medina,2 Michelle Pedroza Jorge,2 Lidio Gonçalves Lima Neto,3 Viviane Hass,4 Xin Li,5 Ana Lucia Tasca Gois Ruiz,2 Deepak Saxena,5 Mary Ann Foglio2 1Sao Leopoldo Mandic Medical School, Araras, São Paulo, Brazil; 2Faculty of Pharmaceutical Sciences at University of Campinas, Campinas, São Paulo, Brazil; 3Postgraduate Program in Parasitic Biology, CEUMA University, São Luis, Maranhão, Brazil; 4School of Dentistry, University of Missouri-Kansas City, Kansas City, MO, USA; 5College of Dentistry, New York University, New York, NY, USACorrespondence: Mary Ann FoglioFaculty of Pharmaceutical Sciences at University of Campinas, Rua Candido Portinari 200, CEP: 13083-871, Campinas, São Paulo, BrazilTel +55 19 3521-8132Email maryann.foglio@fcf.unicamp.brIntroduction: Osteonecrosis of the jaw is a condition associated with intraoral ulceration and bone necrosis induced by antiresorptive medications, such as zoledronic acid, a bisphosphonate. Previous data on Arrabidaea chica (H&B.) Verlot wound healing activity prompted the study reported herein on A. chica standardized hydro alcoholic extract in vitro cytoprotective activity data on epithelial and osteoblastic cells exposed to zoledronic acid (ZA).Methods: Primary human gingival fibroblasts and murine pre-osteoblasts were treated with ZA 10 μM together with 5 or 10 μg.mL− 1 A. chica extract for 24h and 48 h. At both times, cells were submitted to viability assay and caspase 3/7 activation evaluation. Statistical analysis used one-way ANOVA and p=0.05.Results: In cell viability assay, a drastic damage effect of ZA appeared after 48 h in both epithelial (55.8%) and pre-osteoblastic cells (39.7%). When treated with ZA in combination with A. chica extract, cells showed higher viability values: 74.1%– 82.3% for fibroblasts and 66% for pre-osteoblasts. Furthermore, the combined treatment presented lower caspase 3/7 activation in fibroblasts and pre-osteoblasts.Conclusion: At low concentrations, A. chica extract showed promising cytoprotective effects against ZA-induced damage actions; however, further in vitro and in vivo studies are required to establish the mechanism of action.Keywords: Arrabidaea chica, zoledronic acid, epithelial cells, osteoblasts, fibroblasts

Viviane Hass,1 Stephanye Tavares Carvalhal,2 Suellen Nogueira Linares Lima,2 Andrés Alejandro Viteri-Garcia,3 Etevaldo Matos Maia Filho,2 Matheus Coelho Bandeca,2 Alessandra Reis,4 Alessandro Dourado Loguercio,4 Rudys Rodolfo De Jesus Tavarez2 1Postgraduate Program in Dentistry, UNOPAR-University Northern Parana, Londrina, PR, Brazil; 2Postgraduate Program in Dentistry, University Ceuma, São Luis, Brazil; 3Escuela de la Salud Eugenio Espejo, Universidad UTE, Quito, Ecuador; 4Department of Restorative Dentistry, School of Dentistry, State University of Ponta Grossa, Ponta Grossa, BrazilCorrespondence: Alessandro Dourado LoguercioUniversidade Estadual de Ponta Grossa. Departamento de Odontologia Restauradora, Avenida Carlos Cavalcanti 4748 – Uvaranas, Ponta Grossa 84030-900, PR, BrazilEmail aloguercio@hotmail.comObjective: The purpose of this single-blind (evaluators) and parallel design study was to evaluate whether exposure to a cola-based soft drink during bleaching treatment with 35% hydrogen peroxide (HP) affects color change and bleaching-induced tooth sensitivity.Material and methods: Forty-four patients with central incisors darker than A2 were selected. Participants who did not drink cola-based soft drinks were assigned to the control group (CG), while participants who drank a cola-based soft drink at least twice a day were assigned to the experimental group (EG). For the CG, foods with staining dyes were restricted. For the EG, there was no restriction on food and patients were asked to rinse their mouths with a cola-based soft drink for 30 s, 4 times daily. For both groups, 2 sessions with three 15 min applications of 35% HP were performed. Shade evaluation was assessed via subjective (VITA classical and VITA bleacheguide shade guides) and objective methods (Easyshade spectrophotometer) at baseline, during bleaching (first, second, and third weeks), and post bleaching (1 week and 1 month). Patients recorded their sensitivity perceptions using a numerical rating scale and 0–10 visual analog scales. Variation in shade guide units and the 2 colors (DE) were evaluated with a Student’s t-test (α = 0.05) and Mann–Whitney test (α = 0.05). Absolute risk of tooth sensitivity and intensity of tooth sensitivity were evaluated by a Chi-square test (α=0.05).Results: Effective bleaching was observed for both groups after 30 days, without statistical difference (p > 0.08). There was no significant difference in absolute risk of bleaching-induced tooth sensitivity between the 2 groups (p = 0.74). Higher and significant scores in pain scales were detected for the EG in comparison to the CG (p < 0.05).Conclusion: Even that the cola-based soft drink exposure during in-office bleaching treatments did not affect the bleaching’s effectiveness; patients reported a higher intensity in bleaching-induced tooth sensitivity.Keywords: dentin sensitivity, dental bleaching, hydrogen peroxide, cola-based soft drink, carbonated beverages, cola, soda

Purpose: To investigate the antibacterial effects of Terminalia catappa Linn (TCL) leaf extracts at different concentrations and the effects of these extracts used as primers on the long-term adhesive properties of two universal adhesives., Materials and Methods: After extract preparation, the antimicrobial and antibacterial activities of TCL against Streptococcus mutans (UA 159) were assessed in microdilution assays to provide the minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC). Additionally, to provide quantitative data on the ability of TCL extract to reduce cell viability, colony forming units (CFU) were counted. To examine adhesive properties, 288 human molars were randomly assigned to 32 experimental conditions (n = 9) according to the following variables: (1) treatment agent: negative control (untreated surface), and primers at concentrations of 1xMIC, 5xMIC, and 10xMIC; (2) adhesives: Scotchbond Universal (SBU) and Futurabond Universal (FBU); (3) adhesive strategy: etch-and-rinse (ER) or self-etch (SE); and (4) storage time: 24 h or after 2 years. Primers were applied for 60 s, upon which the teeth were incrementally restored and sectioned into adhesive-dentin bonded sticks. These were tested for microtensile bond strength (μTBS) and nanoleakage (NL) after 24-h and 2-year water storage, as well as in-situ degree of conversion (DC) at 24 h. The chemical profile of the hybrid layer was determined via micro-Raman spectroscopy. Biofilm assay data were analyzed using the Kruskal-Wallis test; the pH of culture media and the chemical profile were analyzed by one-way ANOVA. The adhesive properties (µTBS, NL, DC) were evaluated using a four-way ANOVA and Tukey's test. Significance was set at 5%., Results: Similar values of MIC and MBC were observed (2 mg/ml), showing bactericidal potential. CFU analysis demonstrated that concentrations of 5xMIC and 10xMIC significantly inhibited biofilm formation (p < 0.001). The application of the TCL primer at all concentrations significantly increased the immediate μTBS and DC, and decreased the immediate NL values when compared to the control group (p < 0.05), regardless of the adhesive and adhesive strategies. Despite an increase in the NL values for all groups after 2 years (p > 0.05), in groups where the TCL primer was applied, the μTBS remained constant after 2 years for both adhesives, while a decrease in the μTBS was observed in the control groups (p < 0.05). Usually, 10xMIC showed better results than 1xMIC and 5xMIC (p < 0.05). The application of TCL promoted cross-linking; cross-linking rates increased proportionally to the concentration of TCL (p < 0.05)., Conclusion: Primers containing TCL promoted bactericidal and bacteriostatic action, as well as cross-linking with dentin, while maintaining the adhesive properties of the adhesive-dentin interface after 2 years of water storage.

Objective: To evaluate the effect of prolonged (P) polymerization time of a universal adhesive system applied in etch-and-rinse (ER) or self-etch (SE) strategies on the clinical performance of restorations in non-carious cervical lesions (NCCLs), after 36 months of clinical service., Methods: A total of 140 restorations were randomly placed in 35 subjects according to the polymerization time groups: ER (10 s); ER-P (40 s); SE (10 s); and SE-P (40 s) at 1,200 mW/cm 2 . Composite resin was placed incrementally. The restorations were evaluated immediately and after 6, 12, 18, and 36 months using the FDI criteria. Data were analyzed using the Kaplan-Meier survival test for retention loss, and the Kruskal-Wallis' test for secondary outcomes (α = 0.05)., Results: After 36 months, 19 restorations were lost: ER 6, ER-P 2, SE 9, SE-P 2. The retention rates were 82.3% for ER; 94.1 % for ER-P; 73.5 % for SE; and 94.1 % for SE-P, with a significant difference between ER vs. ER-P and SE vs. SE-P, as well as ER vs. SE-P and ER-P vs. SE (p < 0.0001). Minor defects were observed in 18 restorations for the marginal staining criteria: ER 5, ER-P 2, SE 8, SE-P 3; and in 33 restorations for the marginal adaptation criteria: ER 11, ER-P 4, SE 12, and SE-P 6 (p > 0.05). No restorations showed recurrence of caries or postoperative sensitivity., Conclusions: A prolonged polymerization time of 40 s improves the clinical performance of the universal adhesive for both adhesive strategies evaluated, even after 36 months., Clinical Significance: Prolonging the polymerization time of a universal adhesive from 10 to 40 s has been shown to improve its clinical performance when used in NCCLs., Competing Interests: Declaration of competing interest Declarations of interest: The authors of the article entitled “Prolonged Polymerization of a Universal Adhesive in Non-Carious Cervical Lesions: 36-month Double-Blind Randomized Clinical Trial” certify that they have NO affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript., (Copyright © 2023. Published by Elsevier Ltd.)

Objectives: To evaluate the influence of the sonic device on the clinical performance of one-step self-etch adhesive systems in non-carious cervical lesions (NCCLs) after 18 months., Materials and Methods: Forty patients participated in this study. Eighty restorations were assigned to two groups (n = 40): Sonic application and Manual application. After the adhesive application (iBond Self-Etch, Kulzer, Hanau, Germany), NCCLs were restored using composite resin (Charisma, Kulzer, Hanau, Germany). The restorations were evaluated at baseline and after 18 months both according to the Word Dental Federation (FDI) and the United States Public Health Service (USPHS) criteria. Friedman repeated measures analysis of variance by rank and Wilcoxon test for significance in each pair were applied (α = 0.05)., Results: After 18 months, 38 patients were evaluated. Twenty-three restorations were lost (19 for manual vs. 4 for sonic application). The retention rates (95% confidence interval) were 50% (CI 34.8%-65.1%) for manual application and 84.2% (CI 69.6%-92.6%) for sonic application (p < 0.05). Twelve restorations showed marginal staining (nine for manual vs. three for sonic application; FDI, p < 0.05) and nine some marginal discrepancy (seven for manual vs. two for sonic application; FDI, p < 0.05). No restorations showed postoperative sensitivity and caries recurrence at the time., Conclusion: The sonic application increases the retention rate of iBond Self-Etch after 18 months of clinical evaluation in NCCLs., Clinical Relevance: The application of a simplified self-etch adhesive (iBond Self-Etch) associated to a sonic device seems to be an alternative to improve the clinical behavior in NCCLs., (© 2022 Wiley Periodicals LLC.)

Objectives: To develop dual-functional etchants that could demineralize and stabilize dentin collagen simultaneously, and to assess the effects of these etchants on collagen crosslinking, biostability and resin bonding properties under clinically relevant conditions., Methods: Dual-functional etchants were prepared by mixing 56% glycolic acid and 17% phosphoric acid and adding 1% of theaflavins (TF) or proanthocyanidins from grape seed extract (GSE). The etchant without crosslinker was used as control. The prepared human dentin specimens were treated with the 3 etchants for 30 s and analyzed for chemical interaction using Fourier transform infrared spectroscopy and resistance of the demineralized layer to collagenase degradation using electron microscopy (EM). Resin-dentin interfacial bonding properties were evaluated after 24 h and after 10,000 thermocycling through microtensile bond strength (μTBS), nanoleakage and matrix metalloproteinases (MMPs) activity via in situ zymography. Statistical analysis was done using ANOVA and post- hoc Tuckey's test., Results: Compared to control, TF and GSE dual-functional etchants were able to demineralize dentin, induce collagen crosslinking and protect the demineralized layer from collagenase degradation within 30 s. High resolution EM images showed better protection with TF etchant compared to GSE. There was a significant reduction in μTBS and an increase in nanoleakage and MMPs activity in control after thermocycling (p < 0.05) while these changes weren't seen in dual-functional etchants., Significance: Dual-functional etchants, especially TF containing, provide collagen protection against degradation and result in stable μTBS and less nanoleakage and MMPs activity under clinically relevant conditions., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: Sound, natural dentin collagen can be stabilized against enzymatic degradation through exogenous crosslinking treatment for durable bonding; however, the effect on denatured dentin (DD) collagen is unknown. Hence, the ability of different crosslinkers to enhance/restore the properties of DD collagen was assessed., Methods: Demineralized natural and DD collagen films (7 mm × 7 mm × 7 µm) and beams (0.8 mm × 0.8 mm × 7 mm) were prepared. DD collagen was experimentally produced by heat or acid exposure, which was then assessed by various techniques. All specimens were then treated with 1 wt% of chemical crosslinker 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide/n-hydroxysuccinimide (EDC/NHS) and two structurally different flavonoids-theaflavins (TF) from black tea and type-A proanthocyanidins from cranberry juice (CR) for either 30 s or 1 h. The controls were untreated. Dentin films were assessed for chemical interaction and cross-linking effect by FTIR, biostability against exogenous collagenase by weight loss (WL) and hydroxyproline release (HYP), and endogenous matrix metalloproteinases (MMPs) activity by confocal laser microscopy. Dentin beams were evaluated for tensile properties. Data were analyzed using ANOVA and Tukey's test (α = 0.05)., Results: Compared with natural collagen, DD collagen showed pronounced structural changes, altered biostability and decreased mechanical properties, which were then improved to various degrees that were dependent on the crosslinkers used, with EDC/NHS being the least effective. Surprisingly, the well-known MMP inhibitor EDC/NHS showed negligible effect on or even increased MMP activity in DD collagen. As compared with control, cross-linking induced by TF and CR significantly increased collagen biostability (reduced WL and HYP release, p < 0.05), MMP inhibition ( p < 0.001) and mechanical properties ( p < 0.05), regardless of denaturation., Conclusions: DD collagen cannot or can only minimally be stabilized via EDC/NHS crosslinking; however, the challenging substrate of DD collagen can be enhanced or restored using the promising flavonoids TF and CR.

Objectives: This study aimed to evaluate the effect of copper nanoparticles (CuNp) on the clinical performance of a universal adhesive system used as an etch-and-rinse or self-etch strategy., Methods: A total of 216 class V (non-carious lesions) restorations were randomly placed in 36 subjects according to the following groups: ERcu, adhesive in etch-and-rinse with 0.1% CuNp; ERct, adhesive in etch-and-rinse without CuNp; SEcu, adhesive in self-etch with 0.1% CuNp; and Sect, adhesive in self-etch without CuNp. Restorations were evaluated at baseline and at 6, 12, 18, 36, and 48 months, using the FDI and USPHS criteria. Appropriate statistical analyses were performed (α = 0.05)., Results: After 48 months, 14 restorations were lost (two for ERcu, five for SEcu, and seven for SEct) and the retention rates (95% confidence interval [CI]) were 74.1% for ERcu (95% CI 61.1-83.8); 81.5% for ERct (95% CI 69.2-89.6); 64.8% (95% CI 51.5-76.2) for SEcu; and 64.8% (95% CI 51.5-76.2) for SEct, with statistical differences between SEct vs. ERct and SEcu vs. ERct (p < 0.05). No significant differences between the groups were observed when the secondary parameters were evaluated (p > 0.05). Nineteen restorations (two for ERcu, two for ERct, six for SEcu, and nine for SEct) showed minor marginal staining, and 44 restorations (7 for ERcu, 8 for ERct, 14 for SEcu, and 15 for SEct) presented minimal marginal adaptation defects., Significance: This is the first long-term clinical trial to show that the addition of CuNp to a universal adhesive system does not affect clinical performance., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Viral infections are some of the most common sources of respiratory illness in pediatric and adult populations worldwide. Influenza and coronaviruses are viral pathogens that could lead to severe respiratory illness and death. More recently, respiratory illness from coronaviruses, accounts for more than 1 million deaths in the United States alone. This article will explore the epidemiology, pathogenesis, diagnosis, treatment, and prevention of severe acute respiratory syndrome caused by coronavirus-2, and Middle Eastern respiratory syndrome., (© 2023 Elsevier Inc. All rights reserved.)

Objectives: This study investigated the ability of modified phosphoric acids containing chlorhexidine (CHX) or grape seed extract (GSE) for promoting simultaneous biomodification during acid etching on bonding properties in caries-affected dentin (CAD)., Materials and Methods: Thirty-two human molars (8 with sound dentin [SD] and 24 naturally CAD) were selected for the study. The SD and CAD were initially exposed, then randomized and etched according to the following groups: (1) SD (SD-CT) and CAD (CAD-CT) both with 37% phosphoric acid, (2) CAD with 2% CHX containing 37% phosphoric acid (CAD-CHX), and (3) CAD with 2% GSE containing 10% phosphoric acid (CAD-GSE). The bonding procedure and composite build-ups were performed after acid etching. Subsequently, they were sectioned in resin-dentin specimens. The specimens were submitted for chemical profiling by micro-Raman, microtensile bond strength (μTBS), failure mode with chemical characterization by FEG/SEM-EDX, and in situ zymography by CLSM. The data from μTBS and CLSM were statistically analyzed (1-way ANOVA and Tukey's test; α = 0.05)., Results: The highest μTBS results were shown for SD-CT in comparison with all CAD groups (p < 0.001), and the lowest for CAD-CT and CAD-CHX (p < 0.001). The etching with CHX did not increase the μTBS for CAD when compared with CT (p = 0.52). However, the etching with GSE improved significantly the μTBS for CAD when compared with CT and CHX (p < 0.001). The chemical profile detected chemical and structural changes in collagen peaks for CAD-CT, which were not detected when the CAD was etched by modified acids. Also, the poorest hybridization ability was detected in CAD for CT, which was significantly improved with modified acids, especially the GSE, as evaluated by chemical profile and failure mode. A significant reduction of MMP activity on CAD was promoted by modified acids in comparison with CT (both p < 0.001)., Conclusions: The GSE-containing acid was able to promote biomodification during the acid etching, increasing the bonding properties and reducing the activity of the MMPs within the hybrid layer., Clinical Relevance: The use of GSE-containing phosphoric acid can be a promising alternative to improve the bonding performance on caries-affected dentin, since it is capable of biomodifying the dentin during the acid etching, without adding any extra step in bonding procedures.

Objective: To investigate the effects of salivary esterases on biostability of collagen treated by galloylated polyphenols., Methods: Human dentin was microtomed into 6-μm-thick films, which were demineralized and treated for 60 s using solutions containing 0.6% and 2% of one of the crosslinkers: tannic acid (TAC), epigallocatechin gallate (EGCG), epigallocatechin (EGC), and N-[3-dimethylaminopropyl]-N'-ethylcarbodiimide hydrochloride (EDC)/N-hydroxysuccinimide (NHS), and for 1 h using EDC/NHS. Half of the treated and untreated (control) films were subjected to human saliva incubation. Collagen biostability was assessed via exogenous protease biodegradation by weight loss and hydroxyproline release, and endogenous MMPs by in situ zymography. The degradation products of galloylated polyphenols (TAC and EGCG) by saliva were monitored using proton nuclear magnetic resonance ( 1 H NMR) and gel permeation chromatography (GPC). The esterase activity of saliva induced by the crosslinkers was also assessed., Results: Collagen films treated with TAC and EGCG exhibited significantly improved biostability (p < 0.05); however, the enhanced biostability was severely reduced after saliva incubation (p < 0.001). For EDC/NHS treated collagen, saliva incubation showed negligible effect on the biostability. 1 H NMR studies confirmed the esterase-catalyzed hydrolysis of the galloyl. GPC measurements showed decreased molecular weight of TAC in saliva indicating its chemical degradation. Both TAC and EGCG showed much higher esterase activity than other treatment groups., Significance: The galloyl group plays important role in collagen crosslinking, inducing higher biostability. However, galloylated polyphenols crosslinked on collagen are highly susceptible to metabolism of human saliva by salivary esterase, dramatically compromising the enhanced biostability., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: This study aimed to evaluate the effect of prolonging polymerization time on the 18 months clinical performance of a universal adhesive system used as etch-and-rinse (ER) and self-etch (SE)., Methods: 140 restorations were randomly placed in 35 subjects according to the following groups: ER10 (light-curing for 10 s); ER40 (light-curing for 40 s); SE10 (light-curing for 10 s) and; SE40 (light-curing for 40 s/1200 mW/cm 2 ). A resin composite was placed incrementally. The restorations were evaluated at baseline and after 18 months by using the FDI criteria. The following outcomes were evaluated: marginal staining, marginal adaptation, spontaneous post-operative sensitivity and recurrence of caries. The differences among the groups were calculated using Friedman repeated measures analysis of variance rank (α = 0.05)., Results: After 18 months the retention/fracture rates were 88.9% (95%CI 74.1-95.6%) for ER10, 94.3% (95%CI 91.4-98.5%) for ER40, 77.2% (95%CI 60.1-87.9) for SE10 and 97.2% (95%CI 85.5-99.9%) for SE40. A significant difference was detected in the retention rate when SE10 was compared to the SE40 (p = 0.01). Also, ER40 showed a significant improvement of the marginal adaptation when compared to ER10 (p = 0.01)., Significance: This is the first study that demonstrates an improvement in the clinical performance of universal adhesive systems in non-carious cervical lesions when prolonged light-cured was applied., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 The Academy of Dental Materials. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate the effects of different polyphenols and solvents on dentin collagen's crosslinking interactions and biostabilization against MMPs and collagenase degradation., Methods: Two polyphenols [proanthocyanidin (PA) and quercetin (QC)] with different water solubility were prepared as treatment solutions using ethanol (EtOH) or dimethyl sulfoxide (DMSO) as solvents. 6-um-thick dentin films were microtomed from dentin slabs of third molars. Following demineralization, films or slabs were subject to 60-s treatment (PA or QC) or no treatment (control) with subsequent extended-rinse with original solvent (EtOH or DMSO) or distilled water (DW). Collagen crosslinking interactions were assessed by FTIR. Biostability was assessed through endogenous MMPs activity via confocal laser scanning microscopy, and exogenous collagenase degradation via weight loss, hydroxyproline release and SEM. Finally, direct collagenase inactivation was also evaluated. Data were analyzed by three-way ANOVA and post-hoc tests (α=0.05%)., Results: Distinct effects of two polyphenols and solvents on collagen crosslinking and biostabilization were observed. Higher crosslinking and biostability efficacy occurred with PA than QC (p<0.001) that demonstrated negligible collagen interactions. With DMSO solvent, efficacy results were significantly reduced with both polyphenols (p<0.05). DMSO-rinse further weakened interactions of PA with collagen, diminishing biostability (p<0.05). Low biostability was detected with QC and DW-rinse, suggesting direct enzymatic inhibition due to physical presence in collagen., Significance: Collagen crosslinking interactions and biostability depend on polyphenol chemical characteristics. Treatment-solution solvents may affect interactions between polyphenols and collagen, specifically, DMSO showed detrimental effects on collagen crosslinking and biostability and should be used with caution., (Copyright © 2021 The Academy of Dental Materials. Published by Elsevier Inc. All rights reserved.)

Objective: The aim of the study was to investigate the effects of methacrylate-functionalized proanthocyanidins (MAPAs) on dentin collagen's bio-stabilization against enzymatic degradation and crosslinking capability., Methods: Three MAPAs were synthesized via varying methacrylate (MA) to proanthocyanidins (PA) feeding ratios of 1:2, 1:1, and 2:1 to obtain MAPA-1, MAPA-2, and MAPA-3, respectively. The three MAPAs were structurally characterized by proton nuclear magnetic resonance ( 1 H NMR) and Fourier transform infrared (FTIR) spectroscopic methods. 5-μm-thick dentin films were microtomed from dentin slabs of third molars. Following demineralization, films or slabs were treated with 1% MAPAs or PA in ethanol for 30 s. Collagen bio-stabilization against enzymatic degradation was analyzed by weight loss (WL) and hydroxyproline release (HYP) of films, as well as scanning electron microscopy (SEM) on dentin slabs. Crosslinking capacity and interactions of MAPAs with collagen were investigated by FTIR. Data were analyzed by ANOVA and Tukey's test (α = 0.05%)., Results: MA:PA feeding ratios affected MAPAs' chemical structures which in turn led to different collagen stabilization efficacy against degradation and varied collagen crosslinking capabilities. Higher collagen stabilization efficacy was detected using MAPA-1 (WL 10.52%; HYP 13.53 μg/mg) and MAPA-2 (WL 5.99%; HYP 11.02 μg/mg), which was comparable to that using PA (WL 8.79%; HYP 13.17 μg/mg) (p > 0.05), while a lower collagen stability occurred in MAPA-3 (WL 38.48%; HYP 29.49 μg/mg), indicating excessive MA-functionalization would compromise its stabilization efficacy. In comparison, complete digestion was detected for untreated collagen (WL 100%; HYP 102.76 μg/mg). The above results were consistent with collagen crosslinking efficacy of the three MAPAs revealed by SEM and FTIR., Significance: A new class of novel polymerizable collagen cross-linkers MAPAs was synthesized and shown that, when appropriate MA:PA ratios were applied, the resulting MAPAs could render high collagen stability and the ability to copolymerize with resin monomers, overcoming the drawbacks of PA. These new polymerizable crosslinkers, when included in adhesives, could lead to long-lasting dentin bonding., (Copyright © 2021 The Academy of Dental Materials. Published by Elsevier Inc. All rights reserved.)

Objective: The aim of the study was to investigate the effects of a novel polymerizable collagen cross-linker methacrylate-functionalized proanthocyanidins (MAPA) on the polymerization, microhardness and leaching of a HEMA-based experimental dental adhesive system., Methods: Three MAPAs were synthesized using different methacrylate (MA) to proanthocyanidins (PA) feeding ratios of 1:2, 1:1, and 2:1 to obtain MAPA-1, MAPA-2, and MAPA-3, respectively. The resulting three MAPAs and PA were added to an experimental adhesive formulated with HEMA and a tri-component photoinitiator system (0.5 wt% CQ/EDMAB/DPIHP) at 1%, 5% and 10% MAPA or PA concentrations (wt%). The adhesive polymerization kinetics was measured continuously in real-time for 10 min using a Fourier-transform infrared spectroscopy (FTIR) with an attenuated total reflectance (ATR) accessory. Degree of conversion (DC) and Vickers microhardness (MH) of cured adhesives were measured at 72 h post-cure. The leaching of cured adhesives in DI water was monitored using UV-vis spectrophotometer. Statistical analysis was performed using one-way and two-way ANOVA, Tukey's (p < 0.05)., Results: The adhesive formulations with 1%, 5% and 10% MAPAs-1, -2, -3 all generated higher rate of polymerization and 10-min DC than the formulations with PA at the same concentrations. At 72 h post-cure, the adhesive formulation with 5% MAPA-2 exhibited significantly higher DC (99.40%) and more than doubled MH (18.93) values than the formulation with 5% PA (DC = 89.47%, MH = 8.41) and the control (DC = 95.46%, MH = 9.33). Moreover, the cured adhesive with 5% MAPA-2 demonstrated significantly reduced PA leaching in comparison with cured adhesive with 5% PA., Significance: Synthesized MAPA is a novel class of polymerizable collagen cross-linker that not only stabilizes dentin collagen via its PA component, but also improves polymerization, mechanical properties and stability of HEMA-based adhesives via its MA component. By inheriting the benefit while overcoming the drawback of PA, MAPA offers a revolutionary solution for improved bond-strength and longevity of dental restorations., (Copyright © 2021 The Academy of Dental Materials. Published by Elsevier Inc. All rights reserved.)

Improving the longevity of composite restorations has proven to be difficult when they are bonded to dentin. Dentin demineralization leaves collagen fibrils susceptible to enzymatic digestion, which causes breakdown of the resin-dentin interface. Therefore, measures for counteracting the enzymatic environment by enhancing dentin collagen's resistance to degradation have the potential to improve the durability of dental composite restorations. This study aimed to evaluate the effects of polyphenol-rich extracts and a chemical cross-linker on the cross-linking interaction, resistance to digestion, and endogenous matrix metalloproteinase (MMP) activities of dentin collagen under clinically relevant conditions. Ten-µm-thick films were cut from dentin slabs of non-carious extracted human third molars. Following demineralization, polyphenol-rich extracts-including grape seed (GSE), green tea (GTE), and cranberry juice (CJE)-or chemical cross-linker carbodiimide with n-hydroxysuccinimide (EDC/NHS) were applied to the demineralized dentin surfaces for 30 s. The collagen cross-linking, bio-stabilization, and gelatinolytic activities of MMPs 2 and 9 were studied by using Fourier-transform infrared spectroscopy, weight loss, hydroxyproline release, scanning/transmission electron microscopy, and in situ zymography. All treatments significantly increased resistance to collagenase degradation and reduced the gelatinolytic MMP activity of dentin collagen compared to the untreated control. The CJE- and GSE-treated groups were more resistant to digestion than the GTE- or EDC/NHS-treated ones ( p < 0.05), which was consistent with the cross-linking interaction found with FTIR and the in situ performance on the acid-etched dentin surface found with SEM/TEM. The collagen films treated with CJE showed the lowest MMP activity, followed by GSE, GTE, and, finally, EDC/NHS. The CJE-treated dentin collagen rapidly increased its resistance to digestion and MMP inhibition. An application of CJE as short as 30 s may be a clinically feasible approach to improving the longevity of dentin bonding in composite restorations.

Objective: This study evaluated the hydrogen peroxide (HP) penetration inside the pulp cavity and the color change of teeth submitted to the 15% carbamide peroxide (CP) nanoparticle bleaching gel at several application times., Materials and Methods: Premolars were divided into nine groups (n = 6) according to 15% CP bleaching agents (nanoparticle and commercial) and to application times (15, 30, 45, and 60 minutes). A negative control was exposed to ultra-purified water. After a whitening procedure, the HP concentration (μg/mL) inside the pulp cavity was assessed via spectrophotometry. The color change (ΔE* and ΔE00*) was evaluated with a spectrophotometer. Data were analyzed via two-way ANOVA and Tukey (α = 0.05)., Results: A lower concentration of HP was detected for CP nanoparticle gel after 30 and 45 minutes of whitening procedure (P = .001). The bleaching groups promoted a higher color change (ΔE* and ΔE00*) regardless of the application time (P = .0001)., Conclusions: The CP nanoparticle gel reduced HP inside the pulp cavity, and showed effective bleaching compared with CP commercial gel., Clinical Significance: Using 15% carbamide peroxide nanoparticle bleaching gel decreased the HP penetration inside the pulp cavity and may decrease bleaching-induced tooth sensitivity in at-home bleaching., (© 2020 Wiley Periodicals LLC.)

Objective: To evaluate the five-year clinical performance of Scotchbond Universal Adhesive (SU; 3M Oral Care, St. Paul, MN, USA) in non-carious cervical lesions (NCCLs) using two evaluation criteria., Methods: Thirty-nine patients participated in this study. Two hundred restorations were assigned to four groups: SU-ERm: etch-and-rinse + moist dentin; SU-ERd: etch-and-rinse + dry dentin; SU-Set: selective enamel etching; and SU-SE: self-etch. A nanofilled composite resin was placed incrementally. The restorations were evaluated at baseline and after 5 years using both the World Dental Federation (FDI) and the United States Public Health Service (USPHS) criteria. The survival rates (retention/fractures) were calculated with the Kaplan-Meier and the log-rank test. For the secondary outcomes, Friedman repeated measures analysis of variance by rank was applied (α = 0.05)., Results: After 5 years the recall rate was 86%. The retention/fracture rates were 93% for Erm and ERd, 88.4% for SEet and 81.4% for SE. A significant difference was observed for SE vs. ERd and SE vs. ERm (p = 0.01). Also, marginal discoloration and adaptation showed significant differences with ERm and ERd resulting in fewer marginal discrepancies than SE (p < 0.05)., Significance: After 5 years, the clinical behavior of the universal adhesive in the etch-and-rinse strategy was better when compared to the self-etch strategy. The use of selective enamel etching is highly recommended for the self-etch strategy. The FDI and USPHS evaluation criteria showed similar results after 5 years., (Copyright © 2020 The Academy of Dental Materials. Published by Elsevier Inc. All rights reserved.)

Objective: The present study investigated the ability of a chlorhexidine (CHX)-containing primer (0.2% aqueous solution) to inhibit dentinal enzymes, preserve the hybrid layer (HL) and remain within the HL, after 10 years of aging in artificial saliva at 37°C., Methods: Non-carious extracted molars were assigned to two groups, cut into slabs exposing middle/deep dentin, etched and bonded with Adper Scotchbond 1XT (SB1XT) with or without 0.2% CHX aqueous solution pretreatment. Composite build-ups were made, and the specimens were cut in 1-mm thick bonded sticks. In situ zymography was performed on freshly prepared specimens (T 0 ) and specimens aged for 10 years (T 10-yr ) at 37°C in artificial saliva, to investigate endogenous gelatinolytic activity within the HL. At T 10-yr , specimens were also decalcified and embedded in epoxy resin for TEM analysis. Micro-Raman spectroscopy was performed at T 0 and T 10-yr to evaluate the chemical profiles in intertubular dentin and the HL., Results: In situ zymography showed less pronounced enzymatic activity in the CHX-pretreated group (p<0.05) regardless of aging, maintaining a similar level of fluorescence at T 0 and T 10-yr (p>0.05). TEM results showed that 98% of the HL had been degraded in the control group, while 95% of the HL was intact in the experimental group. Moreover, all the Raman spectra peaks assigned to CHX could be identified only in the CHX-pretreated group (T 0 and T 10-yr )., Significance: In vitro, CHX remains in the HL after 10 years with its inhibitory effect preserved. This may be the underlying factor for HL preservation after this long aging period., (Copyright © 2020 The Academy of Dental Materials. Published by Elsevier Inc. All rights reserved.)

Objectives: The aim of this study was to investigate the effects of collagen cross-linking agents on nanomechanical and bonding properties of eroded dentin (ED), 24 h and 2 years after water storage., Materials and Methods: Human molar dentin surfaces, eroded by soft drinks or citric acid, were acid-etched and treated with primers containing proanthocyanidin (PA) and riboflavin (RI) or were untreated (control) and tested after 24 h and 2 years. After acid etching and adhesive application (Prime&Bond Elect (PBE); Scotchbond Universal (SBU); Tetric n-bond Universal (TEU)), specimens were sectioned into beams and tested for microtensile bond strength (μTBS) and silver nitrate deposition (NL) after 24 h and 2 years. The beams were used to evaluate the 24-h in situ conversion of degree (DC). Nanohardness (NH) and Young's modulus (YM) were evaluated via resin-bonded dentin slices after 24 h and 2 years. A three-way ANOVA and Tukey's test were used for statistical analysis (5%)., Results: For both storage times, ED with citric acid resulted in lower μTBS, NH, and YM and higher NL for each adhesive system than soft drink ED (p < 0.05). After 2 years of water storage, cross-linking primers maintained the μTBS, NH, and YM (p < 0.05) when compared with the control group. Althougth, the NL values decreased for all groups after 2 years of water storage, PA and RI treatments showed NI values lower than control group (p < 0.001). No significant differences were observed between PA and RI treatments (p > 0.05). Cross-linking primers maintain or improve DC (p < 0.03). In general, TEU and SBU yielded higher μTBS, DC, NH, and YM and lower NL than PBE., Conclusion: Cross-linking agents improved the results and maintained the resin-ED interface bonding and nanomechanical properties, without jeopardizing adhesive polymerization., Clinical Relevance: Cross-linking agents are a viable alternative for improving and maintaining resin-ED interface bonding and nanomechanical properties.

Objectives: This systematic review aimed to detect whether acid etching pretreatment would enhance the bond strength of universal adhesives (UAs) to caries-affected dentin before and after aging., Methodology: Two independent researchers reviewed materials published until August 2024 in five databases (Web of Science, PubMed, SciELO, Scopus, Science Direct, and Cochrane Library). The eligibility criteria contained in vitro studies that assessed the bond strength of UAs to caries-affected dentin using etch-and-rinse and self-etch modes, with or without aging. Statistical meta-analysis was performed using inverse variance method by the Review Manager program (p < 0.05)., Results: In total, 26 studies were included in the quantitative analysis. Studies have mostly focused on mild UAs. The application of acid etching did not impact the bond strength of ultra-mild and mild UAs (p > 0.05). Aging considerably reduced the bond strength of mild UAs in etch-and-rinse or self-etch modes (p < 0.05). Bond strength to caries-affected dentin was considerably lower than that to sound dentin in both etching modes (p < 0.05)., Conclusions: Pretreatment with phosphoric acid did not affect the bond strength of mild and ultra-mild UAs to caries-affected dentin. The aging process led to a decrease in the bond strength of mild UAs to caries-affected dentin, irrespective of the application strategy., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Conflict of interest: The authors declare no commercial or associative interest representing a conflict of interest regarding the manuscript. The authors do not have any financial interests or commercial associations to disclose. Ethical approval: This article does not contain any studies with human participants or animals performed by any of the authors. Informed consent: For this type of study, formal consent is not required., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

A promising approach for managing root caries is the use of cross-linking agents to stabilize collagen. However, despite testing various natural and synthetic agents in vitro, their efficacy remains uncertain. The aim of this review was to examine which cross-linking agent performs better in reducing root caries lesion depth and the release of hydroxyproline, which is a marker of collagen degradation. Studies evaluating the impact of cross-linking agents on dentin were included, while studies performed on enamel surface/cell cultures and studies evaluating collagenase inhibitors were excluded, among others. A comprehensive search covered eight databases, and study quality was assessed using the QUINN Tool for in vitro dental studies. Synthesis of the results was done using a Bayesian network meta-analysis to compare agents. Fifty studies involving 31 cross-linking agents were included for qualitative synthesis. The network meta-analysis for lesion depth involved 284 samples across 36 comparisons and ranked cross-linking agents in terms of their caries lesion depth-reducing effect (from best to worst): naringin > quercetin > riboflavin > proanthocyanidins > hesperidin > glutaraldehyde > cranberry > grape seed extract > untreated controls. Only naringin, quercetin, proanthocyanidins, and glutaraldehyde showed statistically significant efficacy over untreated controls. Cranberry extract excelled in reducing hydroxyproline release, followed by proanthocyanidins. In conclusion, proanthocyanidins positively affected both outcomes, suggesting they are prime candidates for translational research. Clinical studies are now essential to evaluate their real-world effectiveness against root caries. PROSPERO-CRD42023404911., (© 2024 Scandinavian Division of the International Association for Dental Research. Published by John Wiley & Sons Ltd.)

We present a new modeling approach for the study and prediction of important process outcomes of biotechnological cultivation processes under the influence of process parameter variations. Our model is based on physics-informed neural networks (PINNs) in combination with kinetic growth equations. Using Taylor series, multivariate external process parameter variations for important variables such as temperature, seeding cell density and feeding rates can be integrated into the corresponding kinetic rates and the governing growth equations. In addition to previous approaches, PINNs also allow continuous and differentiable functions as predictions for the process outcomes. Accordingly, our results show that PINNs in combination with Taylor-series expansions for kinetic growth equations provide a very high prediction accuracy for important process variables such as cell densities and concentrations as well as a detailed study of individual and combined parameter influences. Furthermore, the proposed approach can also be used to evaluate the outcomes of new parameter variations and combinations, which enables a saving of experiments in combination with a model-driven optimization study of the design space., (© 2024 Wiley Periodicals LLC.)