Novel Osteogenic Behaviors around Hydrophilic and Radical-Free 4-META/MMA-TBB: Implications of an Osseointegrating Bone Cement.

Poly(methyl methacrylate) (PMMA)-based bone cement, which is widely used to affix orthopedic metallic implants, is considered bio-tolerant but lacks osteoconductivity and is cytotoxic. Implant loosening and toxic complications are significant and recognized problems. Here we devised two strategies to improve PMMA-based bone cement: (1) adding 4-methacryloyloxylethyl trimellitate anhydride (4-META) to MMA monomer to render it hydrophilic; and (2) using tri-n-butyl borane (TBB) as a polymerization initiator instead of benzoyl peroxide (BPO) to reduce free radical production. Rat bone marrow-derived osteoblasts were cultured on PMMA-BPO, common bone cement ingredients, and 4-META/MMA-TBB, newly formulated ingredients. After 24 h of incubation, more cells survived on 4-META/MMA-TBB than on PMMA-BPO. The mineralized area was 20-times greater on 4-META/MMA-TBB than PMMA-BPO at the later culture stage and was accompanied by upregulated osteogenic gene expression. The strength of bone-to-cement integration in rat femurs was 4- and 7-times greater for 4-META/MMA-TBB than PMMA-BPO during early- and late-stage healing, respectively. MicroCT and histomorphometric analyses revealed contact osteogenesis exclusively around 4-META/MMA-TBB, with minimal soft tissue interposition. Hydrophilicity of 4-META/MMA-TBB was sustained for 24 h, particularly under wet conditions, whereas PMMA-BPO was hydrophobic immediately after mixing and was unaffected by time or condition. Electron spin resonance (ESR) spectroscopy revealed that the free radical production for 4-META/MMA-TBB was 1/10 to 1/20 that of PMMA-BPO within 24 h, and the substantial difference persisted for at least 10 days. The compromised ability of PMMA-BPO in recruiting cells was substantially alleviated by adding free radical-scavenging amino-acid N-acetyl cysteine (NAC) into the material, whereas adding NAC did not affect the ability of 4-META/MMA-TBB. These results suggest that 4-META/MMA-TBB shows significantly reduced cytotoxicity compared to PMMA-BPO and induces osteoconductivity due to uniquely created hydrophilic and radical-free interface. Further pre-clinical and clinical validations are warranted.

Biodrug Suppresses Breast and Colorectal Cancer in Murine Models.

RNA interference (RNAi) remains one of the most promising and emerging strategies for the effective cancer treatment due to its high target specificity and greater potency. However, it is hindered due to lack of appropriate targeting technologies. Therefore, there is an imminent need to develop specific and robust delivery systems for successful gene silencing. Nanotechnology-based strategies have been in place to combat the shortcomings associated with viral-based delivery systems. Herein we describe protocols for successful in vitro and in vivo delivery of gene-specific nucleic acids such as siRNAs and shRNAs using PEI-PGMA nanoparticles for efficient cancer therapy.

Comparison of Various Implant Provisional Resin Materials for Cytotoxicity and Attachment to Human Gingival Fibroblasts.

PURPOSE: The aim of this study was to evaluate the responses of human gingival fibroblast (HGF-1) in contact with provisional materials with various chemical compositions and fabricated using different methods. MATERIALS AND METHODS: A total of 210 specimens in eight experimental groups were used. Groups were divided by chemical compositions (poly[ethyl methacrylate], poly[methyl methacrylate], bis-acryl, and hybrid ceramic) and fabricating methods (direct, indirect, and computer-aided design/computer-aided manufacturing [CAD/CAM]). To evaluate the surface characteristics of each group, roughness, water contact angle, and degree of conversion were measured. The responses of HGF-1 to provisional materials were evaluated with cytotoxicity and cell attachment assay. The roughness, surface energy, degree of conversion, level of cytotoxicity, and cell attachment were compared between groups using one-way analysis of variance (ANOVA) and Tukey's multiple comparison (α = .05). RESULTS: The poly(ethyl methacrylate)-direct/indirect and poly(methyl methacrylate)-direct/indirect groups showed higher roughness than the bis-acryl-direct/indirect, poly(methyl methacrylate)-CAD/CAM, and hybrid ceramic-CAD/CAM groups with statistical significance (P < .05). The poly(ethyl methacrylate)-direct group showed the significantly highest water contact angle, and the hybrid ceramic-CAD/CAM group showed the lowest water contact angle (P < .05). The groups that used indirect fabrication methods showed a higher degree of conversion than those that used direct fabrication methods, regardless of chemical composition (P < .05). The poly(ethyl methacrylate) groups showed significantly lower cell viability than the other groups regardless of fabricating methods (P < .05). The poly(ethyl methacrylate)-direct method group showed the lowest cell attachment, and the hybrid ceramic-CAD/CAM method group showed the highest cell attachment (P < .05). CONCLUSION: Poly(methyl methacrylate) and bis-acryl have lower cytotoxicity to HGF-1 than poly(ethyl methacrylate). Indirect fabrication and CAD/CAM are recommended to prevent residual monomer and achieve high cell attachment. To use direct fabrication methods, the auto-mix system is beneficial for the favorable cell response, as it derives a smooth surface.

Evaluation of physical-mechanical properties, antibacterial effect, and cytotoxicity of temporary restorative materials.

The objective of this study was to compare selective physical-mechanical properties, antibacterial effects and cytotoxicity of seven temporary restorative materials (TRM): five resin-based materials [Bioplic (B), Fill Magic Tempo (FM), Fermit inlay (F), Luxatemp LC (L) and Revotek LC (R)], and zinc oxide-eugenol cement (IRM) and glass ionomer cement (GIC) as the controls. Material and methods The physical-mechanical properties were evaluated by determining microleakage (ML), ultimate tensile strength (UTS) and Shore D hardness (SDH). In addition, the polymerization rate (Pr-1), depth of cure (DC), water sorption and solubility (WS/SL) were evaluated. The antimicrobial effects of the materials were assessed by biofilm accumulation of Streptococcus mutans (BT) and the direct contact test (DCT) by exposure to Enterococcus faecalis for 1 and 24 h, and cytotoxicity by MTT assay. The data were analyzed by ANOVA or Kruskall-Wallis tests, and a complementary post-hoc method (p<0.05). Results Group B, followed by FM and GIC had significantly lower percentages of microleakage in comparison with the other groups; Groups FM and L showed the highest WS, while Groups R and FM showed the significantly lowest SL values (p<0.05). Group R showed the statistically highest UTS mean and the lowest DC mean among all groups. Group F showed the lowest S. mutans biofilm accumulation (p=0.023). Only the Group L showed continued effect against E. faecalis after 1 h and 24 h in DCT. The L showed statistically lower viability cell when compared to the other groups. Conclusions These findings suggest the antibacterial effect of the temporary materials Fill Magic and Bioplic against S. mutans, while Luxatemp showed in vitro inhibition of S. mutans biofilm accumulation and E. faecalis growth. Regarding the cell viability test, Luxatemp was the most cytotoxic and Fill Magic was shown to be the least cytotoxic.

Evaluation of physical-mechanical properties, antibacterial effect, and cytotoxicity of temporary restorative materials

Abstract The objective of this study was to compare selective physical-mechanical properties, antibacterial effects and cytotoxicity of seven temporary restorative materials (TRM): five resin-based materials [Bioplic (B), Fill Magic Tempo (FM), Fermit inlay (F), Luxatemp LC (L) and Revotek LC (R)], and zinc oxide-eugenol cement (IRM) and glass ionomer cement (GIC) as the controls. Material and methods The physical-mechanical properties were evaluated by determining microleakage (ML), ultimate tensile strength (UTS) and Shore D hardness (SDH). In addition, the polymerization rate (Pr-1), depth of cure (DC), water sorption and solubility (WS/SL) were evaluated. The antimicrobial effects of the materials were assessed by biofilm accumulation of Streptococcus mutans (BT) and the direct contact test (DCT) by exposure to Enterococcus faecalis for 1 and 24 h, and cytotoxicity by MTT assay. The data were analyzed by ANOVA or Kruskall-Wallis tests, and a complementary post-hoc method (p<0.05). Results Group B, followed by FM and GIC had significantly lower percentages of microleakage in comparison with the other groups; Groups FM and L showed the highest WS, while Groups R and FM showed the significantly lowest SL values (p<0.05). Group R showed the statistically highest UTS mean and the lowest DC mean among all groups. Group F showed the lowest S. mutans biofilm accumulation (p=0.023). Only the Group L showed continued effect against E. faecalis after 1 h and 24 h in DCT. The L showed statistically lower viability cell when compared to the other groups. Conclusions These findings suggest the antibacterial effect of the temporary materials Fill Magic and Bioplic against S. mutans, while Luxatemp showed in vitro inhibition of S. mutans biofilm accumulation and E. faecalis growth. Regarding the cell viability test, Luxatemp was the most cytotoxic and Fill Magic was shown to be the least cytotoxic.

Cytotoxicity and bioactivity of various pulpotomy materials on stem cells from human exfoliated primary teeth.

AIMS: To investigate the cytotoxicity and bioactivity of several pulpotomy materials: Biodentine (Septodont, Saint-Maur-des-Fosses, France) MTA (Angelus, Londrina, PR, Brazil), Theracal LC (Bisco Inc., Schamburg, IL, USA) and IRM (Dentsply DeTrey GmbH, Konstanz, Germany), after contact with stem cells isolated from human exfoliated primary teeth (SHEDs). METHODOLOGY: SHEDs were cultured in the presence of the eluates of various pulpotomy materials for 24, 48 and 72 h. Cell viability was determined by mitochondrial dehydrogenase enzymatic (MTT) assay. Apoptosis and changes in cell phenotype were evaluated by flow cytometry. Also, an in vitro scratch wound-healing assay was used to determine their effects on cell migration. To assess cell morphology and attachment to the different pulpotomy materials, SHEDs were directly seeded onto the material surfaces and analysed by scanning electron microscopy (SEM). Finally, the deposition of a calcified matrix in presence of these materials was verified by Alizarin Red staining. Statistical analysis was performed with analysis of variance and Bonferroni or Tukey post-test (α = 0.05). RESULTS: Cell viability in the presence of Biodentine eluates was significantly higher to that obtained using complete medium alone (control; P < 0.01) and was also significantly higher than using MTA Angelus from 48 h of incubation (P < 0.01). However, Theracal LC and IRM were associated with low rates of cell viability (P < 0.001). Similar results were obtained in an apoptosis assay. In addition, SHEDs maintained their mesenchymal phenotype in all conditions although their capacity to migrate was higher in the presence of Biodentine. SEM studies revealed a suitable proliferation rate, cell spreading and attachment, especially when using Biodentine and MTA Angelus discs. Finally, Biodentine eluates significantly induced calcified matrix deposition from 7 days of culture (P < 0.01). CONCLUSIONS: Biodentine exhibited better cytocompatibility and bioactivity than MTA Angelus, Theracal LC and IRM.

The Synergistic Effect of Cationic Moieties and GRGDSF-Peptides in Hydrogels on Neural Stem Cell Behavior.

This article reports the behavior of embryonic neural stem cells on a hydrogel that combines cationic, non-specific cell adhesion motifs with glycine-arginine-glycine-aspartic acid-serine-phenylalanine (GRGDSF)-peptides as specific cell adhesion moieties. Therefore, three hydrogels are prepared by free radical polymerization that contains either a GRGDSF-peptide residue (P1), amino ethylmethacrylate as a cationic residue (P2), or a combination of both motifs (P3). For each gel, cross linker concentrations of 8 mol% is used to have a comparable gel stiffness of 8-9 kPa. The cell experiments indicate a synergistic effect of the non-specific, cationic residues, and the specific GRGDSF-peptides on embryonic neural stem cell behavior that is especially pronounced in the cell adhesion experiments by more than doubling the number of cells after 72 h when comparing P3 with P2 and is less pronounced in the proliferation and differentiation experiments.

Comparison of femoral component migration between Refobacin bone cement R and Palacos R + G in cemented total hip arthroplasty: A randomised controlled roentgen stereophotogrammetric analysis and clinical study.

AIMS: The widely used and well-proven Palacos R (a.k.a. Refobacin Palacos R) bone cement is no longer commercially available and was superseded by Refobacin bone cement R and Palacos R + G in 2005. However, the performance of these newly introduced bone cements have not been tested in a phased evidence-based manner, including roentgen stereophotogrammetric analysis (RSA). PATIENTS AND METHODS: In this blinded, randomised, clinical RSA study, the migration of the Stanmore femoral component was compared between Refobacin bone cement R and Palacos R + G in 62 consecutive total hip arthroplasties. The primary outcome measure was femoral component migration measured using RSA and secondary outcomes were Harris hip score (HHS), Hip disability and Osteoarthritis Outcome Score (HOOS), EuroQol 5D (EQ-5D) and Short Form 36 (SF-36). RESULTS: Femoral component migration was comparable between Refobacin bone cement R and Palacos R + G during the two-year follow-up period with an estimated mean difference of 0.06 mm of subsidence (p = 0.56) and 0.08° of retroversion (p = 0.82). Five hips (three Refobacin bone cement R and two Palacos R + G) showed non-stabilising, continuous migration; the femoral cement mantle in these hips, was mean 0.7 mm thicker (p = 0.02) and there were more radiolucencies at the bone-cement interface (p = 0.004) in comparison to hips showing stabilising migration. Post-operative HHS was comparable throughout the follow-up period (p = 0.62). HOOS, EQ5D, and SF-36 scores were also comparable (p-values > 0.05) at the two-year follow-up point. CONCLUSION: Refobacin bone cement R and Palacos R + G show comparable component migration and clinical outcome during the first two post-operative years. Hips showing continuous migration are at risk for early failure. However, this seems to be unrelated to cement type, but rather to cementing technique. Cite this article: Bone Joint J 2016;98-B:1333-41.

RGDS- and SIKVAVS-Modified Superporous Poly(2-hydroxyethyl methacrylate) Scaffolds for Tissue Engineering Applications.

Three-dimensional hydrogel supports for mesenchymal and neural stem cells (NSCs) are promising materials for tissue engineering applications such as spinal cord repair. This study involves the preparation and characterization of superporous scaffolds based on a copolymer of 2-hydroxyethyl and 2-aminoethyl methacrylate (HEMA and AEMA) crosslinked with ethylene dimethacrylate. Ammonium oxalate is chosen as a suitable porogen because it consists of needle-like crystals, allowing their parallel arrangement in the polymerization mold. The amino group of AEMA is used to immobilize RGDS and SIKVAVS peptide sequences with an N-γ-maleimidobutyryloxy succinimide ester linker. The amount of the peptide on the scaffold is determined using 125 I radiolabeled SIKVAVS. Both RGDS- and SIKVAVS-modified poly(2-hydroxyethyl methacrylate) scaffolds serve as supports for culturing human mesenchymal stem cells (MSCs) and human fetal NSCs. The RGDS sequence is found to be better for MSC and NSC proliferation and growth than SIKVAVS.

Microvascular stent anastomosis using N-fibroin stents: feasibility, ischemia time, and complications.

OBJECTIVE: To evaluate a novel microvascular anastomosis technique using N-fibroin stents. STUDY DESIGN: Cylinder stents of 1 mm diameter and 5 mm length were fabricated using N-fibroin from silkworms. In 22 rats, aortas were dissected, and the stent was inserted into the two ends of the aorta and fixed using methylmethacrylate. RESULTS: Stent anastomosis was successful in 21 (96%) rats. The mean ischemia time was 7.4 minutes, significantly shorter than the 15.9 minutes in the control group with conventional sutures (P < .0001). After 4 months, anastomosis was functionally patent in all cases. However, elastic fibers remained interrupted in all stent anastomosis cases, and marked host rejection was evident at the stent anastomosis sites. Around the stents, thrombi were frequent (52%). CONCLUSIONS: Our study demonstrated the basic feasibility of stent anastomosis using N-fibroin stents and reduced ischemia time. However, thrombus formation, frequent and severe abdominal infections, and heavy host rejection remain critical issues.

Effects of 4-META/MMA-TBB Resin at Different Curing Stages on Osteoblasts and Gingival Epithelial Cells.

PURPOSE: To assess the effects of different curing stages of 4-META/MMA-TBB resin on osteoblasts and gingival keratinocytes. MATERIALS AND METHODS: The MC3T3-E1 murine pre-osteoblastic cell line and GE-1 murine gingival epithelial cell line were cultured with mixtures of Super-Bond C&B at different curing stages, and the cell viability was assessed. The alkaline phosphatase (ALP) activity of the MC3T3-E1 cells was also assessed. RESULTS: The majority of the MC3T3-E1 cells died and showed no ALP activity when cultured with 4-META/MMA-TBB resin during the initial curing phase (1 min of curing). A later curing phase of the 4-META/MMA-TBB resin (7 min of curing) showed cytotoxicity at day 1, but the toxic effect was temporary and the proliferative capacity and ALP activity in the cells were similar to control cells at day 7. Completely cured 4-META/MMA-TBB resin (after 1 or 12 h of curing) did not affect the cell viability or ALP activity of the MC3T3-E1 cells. In contrast, 4-META/MMA-TBB resin showed no effect on the GE-1 cells at any stage of curing. CONCLUSION: Although 4-META/MMA-TBB resin during the initial curing phase shows toxic effects on MC3T3-E1 cells, that cytotoxicity is minimal at later curing phases. In contrast, neither the uncured nor cured resins affected the GE-1 cells.

A comparative study of the effects of 4-META/MMA-TBB resin and cyanoacrylate on wound healing of skin defects.

The purpose of this study was to investigate the healing process of wounded skin following the application of cyanoacrylate or a 4-(2-methacryloxyethyl) trimellitic anhydride/methyl methacrylate-tributylborane resin (4-META resin). Those materials were applied to skin wound areas in rats, and the regenerating tissues were biopsied and examined at days 1, 3, 5, 7, and 14. Paraffin-embedded specimens were sectioned and stained with hematoxylin and eosin or with Azan-Mallory stain. Sections were also immunohistochemically stained with Pan-cytokeratin and CD68 antibodies. In cyanoacrylate-treated wounds, CD68-positive cells were observed in the connective tissue and their number increased up to day 5. The wound surface was completely covered by epithelial tissue at day 14. In 4-META resin-treated wounds, CD68-positive cells appeared in the soft-tissue hybrid layer (STHL) and epithelial tissue had migrated under the STHL by day 5. The wound surface was completely covered by epithelial tissue at day 7. CD68-positive cells were distributed over the entire area of the cyanoacrylate-treated wounds, but accumulated under the STHL in the 4-META resin-treated wounds. In conclusion, the results suggest that covering skin defects with a 4-META resin is an effective strategy to promote wound healing compared to cyanoacrylate.

Effect of polymer-based desensitizer with sodium fluoride on prevention of root dentin demineralization.

PURPOSE: To evaluate the effect of a fluoride-containing polymer-based desensitizer on prevention of root demineralization using micro-computed tomography (micro-CT). METHODS: Bovine root dentin blocks were divided into four groups; no treatment (Control); 1% oxalic acid (OA); MS Coat One containing methacrylate-co-p-styrene sulfonic acid (MS polymer) and 1% oxalic acid (MSO); and MS Coat F containing MS polymer, 1% oxalic acid and 3,000 ppm sodium fluoride (MSF). A window of the dentin surface was treated with each solution. The blocks were scanned using micro-CT after demineralization (pH 4.5, 5 hours). The dentin surfaces before and after demineralization were examined by scanning electron microscopy (SEM). Fluoride ion release was measured using a fluoride ion-specific electrode. The data were statistically analyzed using one-way ANOVA and Tukey's test (α = 0.05). RESULTS: MSF showed the lowest mineral loss (3176.5 ± 630.5 vol%µm), which was significantly different from Control (4600.1 ± 1053.4 vol%µm), OA (3992.7 ± 899.0 vol%µm) and MSO (3900.2 ± 645.4 vol%µm). [corrected]. Under the SEM observations, the dentin tubules appeared to be blocked after all desensitizer treatments. After demineralization, the exposure of dentin tubules was clearer in OA and MSO compared to MSF which showed sealed dentin tubules after demineralization. Fluoride ion release was detected only in the MSF group.

Study of the water structure in poly(methyl methacrylate-block-2-hydroxyethyl methacrylate) and its relationship to platelet adhesion on the copolymer surface.

The water structure and platelet compatibility of poly(methyl methacrylate (MMA)-block-2-hydroxyethyl methacrylate (HEMA)) were investigated. The molecular weight (Mn) of the polyHEMA segment was kept constant (average: 9600), while the Mn of the polyMMA segment was varied from 1340 to 7390. The equilibrium water content of the copolymers was found to be mainly governed by the HEMA content. The water structure in the copolymers was characterized in terms of the amounts of non-freezing and freezing water (abbreviated as Wnf and Wfz, respectively) using differential scanning calorimetry. It was found that the Wnf for the copolymers were higher than those estimated from the Wnf for the HEMA and MMA homopolymers and that the amount of excess non-freezing water depended on the polyMMA segment length. In addition, X-ray diffraction analysis revealed that some of the copolymers had cold-crystallizable water. These facts suggested that the polyMMA segments were involved in determining the water structures in the copolymers. Furthermore, the platelet compatibility of the copolymers was improved as compared to that of the HEMA homopolymer. It was therefore concluded that the platelet compatibility of the copolymer was related to the amount of excess non-freezing water.

Biocompatibility of 4-META/MMA-TBB resin used as a dental luting agent.

STATEMENT OF PROBLEM: The bonding and biological properties of currently used luting/cementing materials need to be improved. 4-Acryloyloxyethyl trimellitate anhydride/methyl methacrylate-tri-n-butylborane (4-META/MMA-TBB) resin is primarily used for splinting mobile teeth or treating fractured teeth. It undergoes moisture-resistant polymerization and bonds strongly to dentin and metals. PURPOSE: The purpose of this in vitro study was to compare the biological and biochemical properties META/MMA-TBB resin with those of conventional polymethyl methacrylate (PMMA)-MMA resin and other currently used luting materials in order to determine whether it may be a viable dental luting agent. MATERIAL AND METHODS: The degree of polymerization of 4-META/MMA-TBB resin, PMMA-MMA autopolymerizing resin, 10-methacryloyloxydecyl dihydrogen phosphate-dimethacrylate (MDP-DMA) adhesive resin, and a glass ionomer cement was measured by Fourier-transformed infrared spectroscopy. Free radical production during setting was evaluated by electron spin resonance (ESR) spectroscopy. Rat dental pulp cells cultured on these materials were examined for cell viability, attachment, proliferation, and functional phenotype. RESULTS: The degree of polymerization of 4-META/MMA-TBB resin was 82% thirty minutes after preparation, compared to 66% for PMMA-MMA autopolymerizing resin. ESR spectroscopy revealed free radical production from 4-META/MMA-TBB resin and glass ionomer cement was equivalent 24 hours after preparation, with no spike in radical generation observed. In contrast, free radical production from PMMA-MMA and MDP-DMA adhesive resins was rapid and sustained and 10 to 20 times greater than that from 4-META/MMA-TBB. The percentage of viable dental pulp cells 24 hours after seeding was considerably higher on MDP-DMA and 4-META/MMA-TBB resin than on glass ionomer cement. Cell number, proliferation, and alkaline phosphatase activity were highest on 4-META/MMA-TBB resin and lowest on the glass ionomer cement. CONCLUSIONS: 4-META/MMA-TBB resin is at least as biocompatible, and perhaps even more biocompatible, than other current luting materials, with fast, favorable, and nontoxic polymerization properties. Further in vivo and human studies of 4-META/MMA-TBB resin as a dental luting agent are warranted.

Medicinal facilities to B16F10 melanoma cells for distant metastasis control with a supramolecular complex by DEAE-dextran-MMA copolymer/paclitaxel.

The resistance of cancer cells to chemotherapeutic drugs (MDR) is a major problem to be solved. A supramolecular DEAE-dextran-MMA copolymer (DDMC)/paclitaxel (PTX) complex was obtained by using PTX as the guest and DDMC as the host having 50-300 nm in diameter. The drug resistance of B16F10 melanoma cells to paclitaxel was observed, but there is no drug resistance of melanoma cells to the DDMC/PTX complex in vitro. The cell death rate was determined using Michaelis-Menten kinetics, as the DDMC/PTX complex promoted allosteric supramolecular reaction to tubulin. The DDMC/PTX complex showed a very superior anti-cancer activity to paclitaxel alone in vivo. The median survival time (MST) of the saline, PTX, DDMC/PTX4 (particle size, 50 nm), and DDMC/PTX5 (particle size, 290 nm) groups were 120 h (T/C, 1.0), 176 h (T/C, 1.46), 328 h (T/C, 2.73), and 280 h (T/C, 2.33), respectively. The supramolecular DDMC/PTX complex showed the twofold effectiveness of PTX alone (p < 0.036). Histochemical analysis indicated that the administration of DDMC/PTX complex decreased distant metastasis and increased the survival of mice. A mouse of DDMC/PTX4 group in vivo was almost curing after small dermatorrhagia owing to its anti-angiogenesis, and it will be the hemorrhagic necrotic symptom of tumor by the release of "tumor necrosis factor alpha (TNF-α)" cytokine. As the result, the medicinal action of the DDMC/PTX complex will suppress the tumor-associated action of M2 macrophages and will control the metastasis of cancer cells.

Effect of a self-etching primer and phosphoric acid etching on the bond strength of 4-META/MMA-TBB resin to human enamel.

The purpose of this study was to evaluate the shear bond strength and durability of 4-META/MMA-TBB resin to human enamel. A self-etching primer that contained 4-META (Teeth Primer, TP) and 35-45% or 60-65% concentrations of phosphoric acid (K-Etchant Gel, KE, and Super Bond C&B Red Activator, RA) were used as the surface treatment agents. A methyl methacrylate (MMA)-based self-polymerizing resin (Super-Bond C&B) was used as a luting agent. The shear bond strength was determined both pre and post thermocycling. The results were statistically analyzed with a non-parametric procedure. The post-thermocycling shear bond strength of the TP group was significantly higher than that of other groups, and that of the KE group was significantly higher compared with the RA group. These results demonstrated that 4-META was effective. Furthermore, when the degree of tooth demineralization was compared, surface treatment with less demineralization using TP was the most effective treatment.

Liquid dextran does not increase the elution rate of different antibiotics from bone cement.

PURPOSE: To investigate the possibility of increasing elution of fosfomycin, gentamicin, clindamycin, and vancomycin by the addition of dextran fluid during the cement-mixing phase. METHODS: In 12 test series, we produced standardized, antibiotic-loaded test specimens of cement, with and without addition of dextran, and determined their effectiveness against three reference pathogens in agar diffusion and elution tests. RESULTS: In the test series using combined agents, Refobacin(®)-Palacos(®)R plus fosfomycin continuously produced the largest zone of inhibition, both against methicillin-sensitive Staphylococcus aureus (p = 0.009) and against methicillin-resistant Staphylococcus aureus (p = 0.009). The addition of dextran to the various test series had no useful effect on the size of the zone of inhibition for any of the antibiotics tested. CONCLUSIONS: Dextran supplementation in Refobacin(®)-Palacos(®)R bone cement did not have the hope for positive effect on the elution rate of bound antibiotics.

[Preparation and investigation of MRI-traceable Eudragit-E liquid embolic agent].

OBJECTIVE: To develop and investigate the properties of MRI-traceable Eudragit-E liquid embolic agent (MR-E). METHODS: Polyethylene glycol-modified superparamagnetic iron oxides (PEG-SPIO) was synthesized by chemical co-precipitation method. MR-E was prepared by mixing PEG-SPIO and Eudragit-E liquid embolic agent homogeneously. An in vitro MR phantom study was carried out to measure MR traceability of MR-E and to determine the concentration of PEG-SPIO for further studies. The microcatheter deliverability and sol-gel transition process of MR-E were investigated. MR-E was injected into the kidney of a Japanese white big ear rabbit via an angiographic microcatheter, and detected by MRI. RESULTS: A PEG-SPIO concentration of 2 g/L was considered to be suitable for further studies. MR-E was injected through the microcatheter without any difficulty. MR-E instantly solidified on release into saline. Then 0.2 mL of MR-E effectively embolized distal renal arteries, and MR-E could be detected by MRI in the embolized kidney. CONCLUSION: MR-E seems to be a promising MRI-traceable liquid embolic agent.

Effects of calcium silicate endodontic cements on biocompatibility and mineralization-inducing potentials in human dental pulp cells.

INTRODUCTION: The objective of this study was to evaluate the biocompatibility, inflammatory response, and odontoblastic potential of Biodentine (Septodont, Saint Maur des Fosses, France), Ortho-MTA (OMTA; BioMTA, Seoul, Korea), Angelus-MTA (AMTA; Angelus, Londrina, Brazil), and IRM (Dentsply Tulsa Dental, Tulsa, OK) in human dental pulp cells. The underlying signaling mechanisms were also investigated. METHODS: Biocompatibilities were examined by the 3-(4,5-dimethylthiazolyl-2-yl)-2,5-diphenyltetrazolium bromide assay. Differentiation was assessed by alkaline phosphatase activity, alizarin red S staining, and reverse-transcription polymerase chain reaction for marker genes. The levels of inflammatory mediators and cytokines were measured by reverse-transcription polymerase chain reaction and enzyme-linked immunosorbent assay. Signal transduction analysis was performed by Western blotting. RESULTS: Biodentine, OMTA, and AMTA showed favorable cell proliferation, alkaline phosphatase activity, formation of mineralized nodules, and expression of odontoblastic marker genes that were similar to those of IRM. The levels of proinflammatory mediators including nitric oxide, prostaglandin E2, inducible nitric oxide synthase, and cyclooxygenase-2 were lower for Biodentine, OMTA, and AMTA compared with the IRM group. All test materials induced reactive oxygen species production and the expression of hemeoxygenase-1, nuclear factor-E2-related factor-2, and mitogen-activated protein kinases. CONCLUSIONS: These data indicate for the first time that the biocompatibility, inflammatory response, and odontoblastic differentiation of Biodentine were similar to that of OMTA and AMTA in HDPCs, which suggests that Biodentine could be good alternative pulp capping agent.