Size-dependent bioactivity of electrosprayed core-shell chitosan-alginate particles for protein delivery.

Nano-bio interactions are size-dependent. The present study investigates whether core-shell chitosan-alginate particle size governs biological activities as well as protein release profile. A coaxial electrospraying was used to fabricate bovine serum albumin (BSA)-loaded core-shell micro/nanoparticles and were fully characterized. The bio/hemocompatibility of the particles was assessed using MTT and hemolytic assays, respectively, followed by the uptake assessment using flow cytometry. Finally, protein absorption was investigated using SDS-PAGE. The SEM size of the microparticles, the hydrodynamic, and the actual sizes of the nanoparticles were 1.2 µm, 90.49 nm, and 50 nm, respectively. Interactions among two polymers and BSA were observed using DSC analysis. BET analysis showed a more surface area for nanoparticles. A sustained release trend of BSA was observed after 14- and 10-day for microparticles and nanoparticles, respectively. Microparticles exhibited excellent hemocompatibility (< 5% hemolysis) and cell viability (at least > 70%) in all concentrations. However, acceptable hemolytic activity and cell viability were observed for nanoparticles in concentrations below 250 µg/mL. Furthermore, nanoparticles showed greater cellular uptake (~ 4 folds) and protein absorption (~ 1.61 folds) than microparticles. Overall, the developed core-shell chitosan-alginate particles in the micro/nanoscale can be promising candidates for biomedical application and regenerative medicine regarding their effects on above mentioned biological activities.

The Role of Growth Factor Delivery Systems on Cellular Activities of Dental Stem Cells: A Systematic Review (Part II).

OBJECTIVE: The current systematic review aims to provide the available ex vivo evidence evaluating the biological interactions of dental stem cells (DSCs) and growth factor delivery systems. METHODOLOGY: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a systematic search was conducted in the electronic databases (PubMed/Medline, Scopus, Web of Science, and Google Scholar) up to January 2022. Studies evaluating the biological interactions of DSCs and growth factor delivery systems were included. The outcome measures were cell cytocompatibility, mineralization, and differentiation. RESULTS: Sixteen studies were selected for the qualitative synthesis. The following growth factor delivery systems exhibit adequate cytocompatibility, enhanced mineralization, and osteo/odontoblast differentiation potential of DSCs: 1) Fibroblast growth factor (FGF-2)-loaded-microsphere and silk fibroin, 2) Bone morphogenic protein-2 (BMP-2)-loaded-microsphere and mesoporous calcium silicate scaffold, 3) Transforming growth factor Betha 1 (TGF-ß1)-loaded-microsphere, glass ionomer cement (GIC), Bio-GIC and liposome, 4) TGF-ß1-loaded-nanoparticles/scaffold, 5) Vascular endothelial growth factor (VEGF)-loaded-fiber and hydrogel, 6) TGF-ß1/VEGF-loaded-nanocrystalline calcium sulfate/hydroxyapatite/calcium sulfate, 7) Epidermal growth factor-loaded- nanosphere, 8) Stem cell factor/DSCs-loaded-hydrogel and Silk fibroin, 9) VEGF/BMP-2/DSCs-loaded-Three-dimensional matrix, 10) VEGF/DSCs-loaded-microsphere/hydrogel, and 11) BMP-2/DSCs and VEGF/DSCs-loaded-Collagen matrices. The included delivery systems showed viability, except for Bio-GIC on day 3. The choice of specific growth factors and delivery systems (i.e., BMP-2-loaded-microsphere and VEGF-loaded-hydrogel) resulted in greater gene expression. CONCLUSIONS: This study, with low level evidence obtained from ex vivo studies, suggests that growth factor delivery systems induce cell proliferation, mineralization, and differentiation towards a therapeutic potential in regenerative endodontics.

Effects of Growth Factors on Cellular Activities of Dental Stem Cells: A Systematic Review and Meta-analysis (Part I)

INTRODUCTION: To evaluate the biological interaction between dental stem cells (DSCs) and different growth factors in the field of regenerative endodontics. METHODS: A systematic search was conducted in the electronic databases up to October 2021. This study followed the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. Ex vivo studies evaluating the biological interactions of DSCs and growth factors were included. The meta-analysis was performed according to the type of growth factor. The outcomes were cell viability/proliferation and mineralization. Standardized mean differences (SMDs) were estimated using the random-effect maximum-likelihood method (P<.05). Additional analysis was performed to find any potential source of heterogeneity. RESULTS: Twenty articles were included in the systematic review; meta-analysis was performed for fibroblast growth factor-2 (FGF-2) and Transforming growth factor-ß1 (TGF-ß1) (n=5). Results showed that use of FGF-2 significantly increased cell proliferation on day 1-(SMD=3.56,P=0.00), 3-(SMD=9.04,P=0.00), 5-(SMD=8.37,P=0.01), and 7 (SMD=8.51,P=0.00) than the control group. TGF-ß1 increased alkaline phosphatase (ALP) activity more than control only on day 3 (SMD=3.68,P=0.02). TGF-ß1 had no significant effect on cell proliferation on days 1 and 3 (P>0.05) and on ALP activity on days 5 and 7 (P>0.05). Meta-regression analysis showed that different covariates (i.e., cell type, passage number, and growth factors' concentration) could significantly influence the effect sizes at different follow-ups (P<0.05). CONCLUSION: Specific growth factors might enhance the proliferation and mineralization of DSCs; however, the obtained evidence was weak. Due to the high heterogeneity among the included studies, other growth factors' inhibitory/stimulatory effects on DSCs could not be evaluated.

Cytokine co-stimulation effect on odontogenic differentiation of stem cells.

OBJECTIVE: The study aims to evaluate the effect of bone morphogenetic protein-2 (BMP-2) and transforming growth factor-beta 1 (TGF-ß1) co-stimulation on odontogenic differentiation of human dental pulp stem cells (hDPSCs). MATERIALS AND METHODS: The viability/proliferation of hDPSCs treated with BMP-2 (group B), TGF-ß1 (group T), or BMP-2/TGF-ß1 (group BT) were evaluated. The experiments on odontogenic differentiation were done for 14 days. The following subgroups were added to investigate the effect of co-stimulation with different timing: subgroup B1, TGF-ß1 co-stimulation in the first week; subgroup B2, TGF-ß1 co-stimulation in the second week; subgroup T1, BMP-2 co-stimulation in the first week; and subgroup T2, BMP-2 co-stimulation in the second week. The mineralization was assessed using alizarin red staining. The expression of following genes was assessed using quantitative real-time polymerase chain reaction: dentin sialophosphoprotein (DSPP), dentin matrix protein-1 (DMP1), osteopontin (OPN), and alkaline phosphatase. RESULTS: All groups showed viability similar to the control group (P > .05). The greater mineralization was detected in B groups on day 14. The expressions of DSPP, DMP-1, and OPN increased on day 14 (P < .05). In the combination groups, the higher expressions of DSPP and DMP-1 were observed in subgroups B1 and B2 than groups B and T (P < .05). CONCLUSIONS: BMP-2 was the key in odontogenic differentiation of hDPSCs, which was further enhanced by co-stimulation with TGF-ß1. Continuous stimulation with TGFß-1 did not improve the differentiation of hDPSCs. CLINICAL RELEVANCE: Combined use of the BMP-2 and TGFß-1 at the specific sequence can provide a tissue engineering approach for the future guided dentin regeneration.

Effects of antibiotic administration on post-operative endodontic symptoms in patients with pulpal necrosis: A systematic review and meta-analysis.

OBJECTIVES: The current systematic review and meta-analysis aimed to assess the efficacy of prophylactic oral antibiotics in the management of post-operative endodontic symptoms in adults with necrotic pulp. MATERIALS AND METHODS: A systematic search up to April 2020 was performed to find all randomised controlled trials (RTCs) comparing oral antibiotics with placebo to manage post-endodontic symptoms. The outcome measures were post-operative pain, swelling and/or the combined pain and swelling at different follow-ups. Standardised mean differences (SMDs) and 95% confidence intervals (CIs) were estimated using random-effect inverse-variance method. Additional analysis was performed if heterogeneity existed (P < .05). RESULTS: For post-endodontic pain, 8 RCTs (n = 690) were included. Antibiotic prescription had no significant effect on endodontic pain at 6 (SMD = -0.008, 95% CI -0.279 - 0.264, P = .95), 12 (SMD = -0.080, 95% CI -1.39 - 1.23, P = .90), 24 (SMD = -0.044, 95% CI -0.29 - 0.20, P = .72), 48 (SMD = 0.18, 95% CI -0.26 - 0.62, P = .42) and 72 h (SMD= -0.050, 95% CI -0.33 - 0.23, P = .723) post-operatively. For post-endodontic swelling, 4 RCTs (n = 149) were included. Antibiotic prescription had no significant effect on endodontic swelling at 24 (SMD = 0.29, 95% CI -0.72 - 1.32, P = .56), 48 (SMD = -0.23, 95% CI -0.98 - 0.51, P = .54) and 72 hours (SMD= -0.03, 95% CI -1.25 - 1.33, P = .96), post-operatively. For combined pain and swelling, no meta-analysis was performed. CONCLUSION: The administration of prophylactic antibiotics to prevent post-operative endodontic symptoms is not supported by the current evidence.

Shade reproduction and the ability of lithium disilicate ceramics to mask dark substrates.

OBJECTIVES: This study aimed to evaluate the ability of lithium disilicate ceramics to reproduce the A2 shade and to mask A4 substrates. MATERIALS AND METHODS: Twenty-four discs (8 mm in diameter, shade A2) of high translucency (groups 1-3) and low translucency (groups 4-6) of IPS e.max ceramic with different thicknesses (0.5, 0.75, and 1 mm) were fabricated as monolithic structures. In addition, discs of medium opacity (group 7-8) with different core/veneer combinations (0.3 mm/0.7 mm and 0.5 mm/0.5 mm) were fabricated as bilayer structures. Specimens were superimposed on an A4 substrate (complex). The color changes of the complex were measured using a spectrophotometer on a black background, and the ΔE values of the complex were compared with either the A4 substrate or the A2 shade tab. One-way analysis of variance, the Tukey honest significant difference test, and the Fisher test were used to analyze the data (p < 0.05). RESULTS: Significant between-group differences were found for comparisons to both the A4 substrate and the A2 shade (p < 0.05). When compared with the A4 substrate, the ΔE values in all groups were in the non-acceptable range. When compared with the A2 shade, the ΔE values in all groups, except groups 2 and 3, were in the clinically acceptable range. CONCLUSIONS: All translucencies and thicknesses masked the underlying dark substrate. However, the low-translucency IPS e.max Press better reproduced the A2 shade.

Does occlusal reduction reduce post-endodontic pain? A systematic review and meta-analysis.

OBJECTIVES: Pain management during endodontic therapy is an important issue in clinical practice. The objective of this systematic review and meta-analysis was to evaluate the efficacy of occlusal reduction to control the post-operative endodontic pain in adults undergoing root canal therapy. MATERIALS AND METHODS: Electronic database and manual searches of English papers were conducted up to August 2019 to identify randomised placebo-controlled trials. The MeSH terms used were (endodontics OR root canal therapy) AND (postoperative pain) AND (occlusal reduction). The primary outcome measure was the post-operative pain intensity up to 72 hours. Pooled standardised mean differences (SMDs) and 95% confidence intervals (CIs) were calculated using random-effects inverse variance method. The statistical heterogeneity was assessed using the Cochrane Q test. The significance level was set at P < .05. RESULTS: In total, six randomised controlled trials including 344 participants were included. Our meta-analyses showed that relief of occlusal surface did not significantly reduce the pain intensity scores at 12- (SMD = -0.46; 95% CI = -1.24, 0.30; P = .239), 24- (SMD = -0.17; 95% CI = -0.73, 0.38; P = .533) and 48- (SMD = -0.67; 95% CI = -1.38, 0.03; P = .063) when compared to placebo. However, at 72 hours, patients received intervention showed significant more pain reduction than placebo groups (SMD = -1.07; 95% CI = -1.81, -0.32; P = .005). CONCLUSION: Based on this meta-analysis, the efficacy of occlusal reduction in post-endodontic pain control for up to 2 days is not supported. However, on day three, it had a positive influence on the control of post-endodontic pain.

Regenerative Endodontics: A Scientometric and Bibliometric Analysis.

INTRODUCTION: Scientometric analyses outline the research output in a field and, therefore, help researchers and funding agencies to focus more on underinvestigated areas and make more efficient decisions related to public health. The aim of this study was METHODS: Electronic searches were done in MEDLINE and Scopus databases using specified search criteria. All articles related to the field of regenerative endodontics until December 2017 were included. The total number of publication/year and the yearly growth rate of publications were calculated. The following data were extracted and analyzed: authors, country of origin, journal, number of citations, study design, and level of evidence (LOE). The visualization maps for authorship/coauthorship, citations, and country of origin of articles were prepared and analyzed. RESULTS: A total of 694 articles were included. The average yearly growth for publications was 40.4% between 2007 and 2017. The highest number of articles were ex vivo/in vitro (n = 342, 49.27%). The distribution of articles based on LOE was as follows: LOE 1, 8.34%; LOE 2, 6.00%; LOE 3, 0.66%; LOE 4, 11.67%; and LOE 5, 73.33%. Collectively, 1820 authors contributed to the publications included in this study: 1001 authors within 40 collaborating clusters and 819 authors within 149 noncollaborating clusters. The United Sates was the lead country regarding the number of publications, citations, and international collaborations. The Journal of Endodontics published the highest number of articles. CONCLUSIONS: The total number of publications in the field of regenerative endodontics shows exponential growth in the past decade. However, the proportion of articles with LOE 1 is low. The research groups around the globe are encouraged to focus their collaborative efforts on higher-quality and clinically oriented research.

Efficacy of Corticosteroids on Postoperative Endodontic Pain: A Systematic Review and Meta-analysis.

INTRODUCTION: The purpose of this systematic review and meta-analysis was to evaluate the effectiveness of corticosteroids on postoperative endodontic pain and to determine/adjust between-trial heterogeneity using meta-regression analysis. METHODS: A systematic literature search was conducted to identify randomized clinical trials using corticosteroids to manage postoperative endodontic pain in adults. The outcome measure was pain intensity scores at 6, 12, and 24 hours postoperatively. Standardized mean differences (SMDs) with their 95% confidence intervals (CIs) were estimated using the random effect inverse variance method. The level of significance was set at P < .05. Meta-regression analysis was also performed to examine the associations between effect sizes and study-level covariates. RESULTS: Eighteen randomized clinical trials, comprising 1088 patients, were included. Corticosteroids significantly reduced the incidence of postoperative pain in endodontic patients at 6 hours (SMD = -1.03; 95% CI, -1.55 to -0.51; P = .000), 12 hours (SMD = -1.089; 95% CI, -1.71 to -0.46; P = .001), and 24 hours (SMD = -0.957; 95% CI, -1.34 to -0.56; P = .000). Meta-regression analysis showed that the type and dose of drug, performing intention-to-treat analysis, and using rescue medication could significantly influence the effect size at different time points. CONCLUSIONS: Corticosteroids had a postoperative pain-reducing effect in endodontic patients, and the choice of drug regimens could be an important predictor of pain reduction.

Hygroscopic expansion of bulk fill composites: A three-month report / Expansão higroscópica de compósitos "bulk fill": um relato de três meses

Polymer networks are considered to be largely affected by water and chemical absorption from environment. Objective: The aim of this study was to evaluate the hygroscopic expansion of bulk-fill composite. Material and Methods: Fifteen disks (5 in each group) with different thickness(4mm/2mm) of Tetric N-Ceram Bulk Fill composite(TB) and Tetric N-Ceram composite(TN) were made according to the manufacturer's instruction and stored in deionized water. The length of each specimen was recorded using a digital micrometer at baseline and at the end of 24 h, 1, 2, 4, 12 weeks intervals. Repeated measure ANOVA and Tukey HSD were used to determine the effect of variables. At 12 weeks, the mean hygroscopic expansion after water immersion ranged between 0. 33±0.09mm for TN to 0.41±0.07mm for TB with 2mm thickness. Repeated measure ANOVA revealed a significant increase in hygroscopic expansion over time (P <0.05). Results: The results indicated that at 24hours and 2weeks there was a significant difference among TN and TB with 4mm thickness (p=0.007 and p=0.023, respectively). The other differences were not significant. Hygroscopic expansion affected by the type of composite and the passing of time. Conclusion: The results showed that the time taken to reach stabilization in hygroscopic expansion was shorter for TN in comparison with TB. For 2mm thickness equilibrium was attained earlier. (AU)

Considera-se que as redes de ligações intrínsecas de polímeros são amplamente afetadas pela absorção de água e produtos químicos do meio ambiente. Objetivo: O objetivo deste estudo foi avaliar a expansão higroscópica do compósito bulk-fill. Material e Métodos: Quinze discos (5 em cada grupo) com diferentes espessuras (4mm / 2mm) de compósito Tetric N-Ceram Bulk Fill (TB) e Tetric N-Ceram (TN) foram confeccionados de acordo com as instruções do fabricante e armazenados em água deionizada. O comprimento de cada espécime foi registrado usando um micrômetro digital no início e no final de 24 h, 1, 2, 4, 12 semanas de intervalo. O teste de medidas repetidas ANOVA e Tukey foram usados para determinar o efeito das variáveis. Às 12 semanas, a expansão higroscópica média após imersão em água variou entre 0,33 ± 0,09mm para NT a 0,41 ± 0,07mm para TB com 2mm de espessura. ANOVA revelou um aumento significativo na expansão higroscópica ao longo do tempo (P <0,05). Resultados: Os resultados indicaram que às 24h e 2 semanas houve diferença significativa entre TN e TB com 4mm de espessura (p=0,007 e p=0,023, respectivamente). As outras diferenças não foram significativas. A expansão higroscópica foi afetada pelo tipo de compósito e pelo tempo. Conclusão: Os resultados mostraram que o tempo necessário para alcançar a estabilização na expansão higroscópica foi menor para TN em comparação com TB. Para 2 mm de espessura o equilíbrio foi atingido mais cedo. (AU)

Effect of preoperative oral analgesics on pulpal anesthesia in patients with irreversible pulpitis-a systematic review and meta-analysis.

OBJECTIVES: The objectives of this study were to assess the efficacy of preemptive oral administration of single dose of non-steroidal anti-inflammatory drugs (NSAIDs) and acetaminophen on the local anesthetic success in adults with irreversible pulpitis and to find the possible covariates that could predict treatment effect. MATERIALS AND METHODS: A systematic search using electronic databases up to March 2015 was conducted. Odds ratio (OR) and 95% confidence intervals (CIs) were estimated using random and fixed-effect inverse variance method. Subgroup and meta-regression analyses were conducted to assess the potential source of heterogeneity. RESULTS: Results showed that preemptive analgesics are more effective than placebo in increasing anesthetic success (OR = 0.30, CI% 0.24-0.39, p = 0.000) [Q = 55.860 (p = 0.001)]. In the subgroup analysis, administration of NSAIDs as monotherapy, ibuprofen as mono- vs. combination therapy, oxicam type drugs as monotherapy, and acetaminophen as combination therapy were significantly more effective in increasing anesthetic success OR = 0.25, CI% 0.16-0.38, p = 0.00, Q = 40.539 (p = 0.003); OR = 0.44, CI% 0.26-0.75, p = 0.00, Q = 12.833 (p = 0.011); OR = 0.48, CI% 0.30-0.74, p = 0.002, Q = 15.898 (p = 0.14); OR = 0.30, CI% 0.16-0.38, p = 0.001, Q = 7.506 (p = 0.02); OR = 0.10, CI% 0.16 0.38, p = 0.001, Q = 5.075 (p = 0.07), respectively. However, there was no significant difference in increasing anesthetic success between treatment and placebo arms when acetaminophen was administrated alone. In meta-regression analysis, an association between different types of NSAIDs (indomethacin, diclofenac potassium, and oxicam-type drugs) and articaine with treatment effect was observed. CONCLUSIONS: The administration of preemptive analgesics can induce superior intraoperative analgesia for patients with irreversible pulpitis. However, strategies such as co-administration of certain types of analgesics and anesthetic solution might be predictors of treatment effect. Additionally, there was no association between different timing and dosage of analgesics and treatment effect. CLINICAL RELEVANCE: When compared to placebo, preemptive oral analgesics are superior in achieving anesthetic success in inflamed pulp.

Color Stability of the Bulk-Fill Composite Resins with Different Thickness in Response to Coffee/Water Immersion.

We aimed to evaluate the color stability of bulk-fill and conventional composite resin with respect to thickness and storage media. Twenty specimens of a conventional composite resin (6 mm diameter and 2 mm thick) and 40 specimens of the bulk-fill Tetric EvoCeram composite resin at two different thicknesses (6 mm diameter and 2 mm thick or 4 mm thick, n = 20) were prepared. The specimens were stored in distilled water during the study period (28 d). Half of the specimens were remained in distilled water and the other half were immersed in coffee solution 20 min/d and kept in distilled water between the cycles. Color changes (ΔE) were measured using the CIE L (⁎) a (⁎) b (⁎) color space and a digital imaging system at 1, 7, 14, and 28 days of storage. Data were analyzed using Two-way ANOVA and Tukey's HSD post hoc test (P < 0.05). Composite resins showed significant increase in color changes by time (bulk-fill > conventional; P < 0.001). Coffee exhibited significantly more staining susceptibility than that of distilled water (P < 0.001). There was greater color changes with increasing the increment thickness, which was significant at 14 (P < 0.001) and 28 d (P < 0.01). Color change of bulk-fill composite resin was greater than that of the conventional one after coffee staining and is also a function of increment thicknesses.

Color stability of mineral trioxide aggregate and calcium enriched mixture cement.

AIM: To assess the effect of light irradiation and different immersion media on discoloration of white mineral trioxide aggregate (WMTA) and calcium enriched mixture (CEM) cement at different time intervals. METHODS: Enamel sections of 12 teeth were removed and six cavities were prepared in each tooth. The cavities were filled randomly either with WMTA or CEM and covered with transparent sealant. Half the specimens were irradiated for 160 sec (eight exposures of 20 sec each) and the remaining were irradiated for 40 sec (two exposures of 20 sec each); digital images were taken after each exposure. The teeth were stored in phosphate buffer saline, oxygen-rich medium and glycerin (n = 4). Digital images were obtained after 1, 3, 7, 14, and 28 days. Commission Internationale de I'E'clairage (CIE) color space system and Photoshop CS5 software were used to evaluate the discoloration. The color change (ΔE) and lightness (ΔL) values was analyzed using repeated measures anova and Tukey's Tukey's honest significant difference (HSD) test. RESULTS: The materials tested showed significant discoloration over time (WMT > CEM; P < 0.001). ΔE increased significantly while ΔL decreased in three media over time (P < 0.001). Greater duration of light curing caused a significant decrease in ΔL and ΔE values in both materials (WMTA > CEM; P < 0.001). CONCLUSION: Color stability of WMTA was inferior to CEM samples after exposure to different duration of irradiation and media over time.