A Lysosome-Targeting Self-Condensation Prodrug-Nanoplatform System for Addressing Drug Resistance of Cancer.

Lysosome-targeting self-assembling prodrugs had emerged as an attractive approach to overcome the acquisition of resistance to chemotherapeutics by inhibiting lysosomal sequestration. Taking advantage of lysosomal acidification induced intracellular hydrolytic condensation, we developed a lysosomal-targeting self-condensation prodrug-nanoplatform (LTSPN) system for overcoming lysosome-mediated drug resistance. Briefly, the designed hydroxycamptothecine (HCPT)-silane conjugates self-assembled into silane-based nanoparticles, which were taken up into lysosomes by tumor cells. Subsequently, the integrity of the lysosomal membrane was destructed because of the acid-triggered release of alcohol, wherein the nanoparticles self-condensed into silicon particles outside the lysosome through intracellular hydrolytic condensation. Significantly, the LTSPN system reduced the half-maximal inhibitory concentration (IC50) of HCPT by approximately 4 times. Furthermore, the LTSPN system realized improved control of large established tumors and reduced regrowth of residual tumors in several drug-resistant tumor models. Our findings suggested that target destructing the integrity of the lysosomal membrane may improve the therapeutic effects of chemotherapeutics, providing a potent treatment strategy for malignancies.

Heterofunctional ruthenium(II) carbosilane dendrons, a new class of dendritic molecules to fight against prostate cancer.

A family of heterofunctional Schiff base carbosilane metallodendrons with [Ru(η5-C5H5)(PTA)Cl] (PTA = 1,3,5-triaza-7-phosphatricyclo-[3.3.1.1]decane) at the focal point and dimethylamino groups on the periphery are described. The new systems have proved their ability to interact with biological molecules such as Human Serum Albumin (HSA) without affecting its secondary structure and erythrocytes membranes, causing haemolysis in a dose and generation dependent way. The combination of two active functional groups in one single dendritic platform has shown a cooperative effect in the viability of HeLa and PC-3 cells, with the second generation derivative standing out as the most promising with the lowest IC50. Experiments focused on advanced prostate cancer have shown an antimetastasic activity for those metallodendrons, hindering the adhesion of cells in one of the main targets of metastasis, bones, and inhibiting cell migration. Finally, the second generation metallodendron with one single metal centre and four dimethylamino groups on the dendritic wedge, was selected for an ex vivo experiment in nude mice with advanced prostate cancer inhibiting the tumour growth in a 40% compared to control mice.

Effect of MDP-Based Silane and Different Surface Conditioner Methods on Bonding of Resin Cements to Zirconium Framework.

PURPOSE: To determine the shear bond strength (SBS) between zirconium framework and resin cements after different surface conditioner methods and after application of 10-methacryloyloxydecyl dihydrogen phosphate (MDP) based silane and a bonding agent mix. MATERIALS AND METHODS: 128 disc-shaped zirconium-oxide specimens were prepared. Specimens were placed in autopolymerizing acrylic resin. The bonding surface of specimens was smoothed consecutively with 600-, 800-, and 1200-grit silicon carbide papers under water cooling. Eight groups were prepared: CJ, Co-Jet; N, Nd-YAG laser; E, Er-YAG laser; NS, Nd-YAG laser + silane; ES, Er-YAG laser + silane; CJB, Co-Jet + bonding agent; NSB, Nd-YAG laser + silane + bonding agent; ESB, Er-YAG laser + silane + bonding agent. SEM analysis was performed under 2000× magnification. Dual- and self-cured resin cements were bonded to specimens, and shear force was applied. Data were analyzed with one-way ANOVA and Tukey's multiple comparison test (p < 0.05). RESULTS: The SBS values differed from each other among the groups. While the CJB group showed the highest values, the N group showed the lowest. The treatment with MDP-based silane and bonding agent mix increased SBS values of each cement belonging to each group. SB values of dual-cure resin cement were higher than those of self-cure resin cements. CONCLUSION: Different surface conditioner methods exhibit an important effect on the SBS of resin cements to zirconium. The application of MDP-based silane and bonding agent mix enhanced SB values.

Bond strength of resin cement to ceramic with simplified primers and pretreatment solutions.

Manufacturers have recently introduced surface primers and pretreatment solutions that reportedly simplify the bonding process of resin cements to ceramics through various combinations of etchant and coupling agents. This study evaluated the shear bond strength (SBS) of a resin cement to a lithium disilicate glass-ceramic material pretreated with various new surface treatment solutions and compared the results to those of a control group prepared with the traditional application of hydrofluoric acid (HF) and silane. Resin cement was bonded to pretreated glass-ceramic surfaces, and specimens were tested for SBS after 24 hours of storage in water. Traditional surface treatment of lithium disilicate glass ceramic with HF and silane resulted in a significantly greater mean SBS than did simplified primer solutions. There were no statistically significant differences among the simplified pretreatment groups. In the control group, the majority of failures were due to mixed adhesive-cohesive fracture, while in the simplified treatment groups the failure mode was usually adhesive, suggesting a weaker interface.

Short- and Long-Term Bond Strength Between Resin Cement and Glass-Ceramic Using a Silane-Containing Universal Adhesive.

This study aimed to evaluate the effect of various silane-containing solutions on bonding between resin cement and glass ceramic after 24 hours and after six months of water storage. Glass-ceramic plaques (IPS e.max CAD) were sandblasted with aluminum oxide, etched with 10% hydrofluoric acid (HF), and divided into five "silane treatment" groups: RelyX Ceramic Primer (RCP), RelyX Ceramic Primer and Single Bond Plus (RCP+SB), Scotchbond Universal (SBU), Clearfil Ceramic Primer (CP), and no solution (HF-only control). Each group was divided into two "storage time" subgroups: 24 hours or six months in 37°C water. Eighteen resin cement cylinders (RelyX Ultimate) were bonded to each treatment group substrate (n=18) and then subjected to microshear testing. Failure mode was analyzed using scanning electron microscopy. Debond data were analyzed using a two-way analysis of variance and the Tukey post hoc test (α=0.05) as well as Weibull distributions. The factors "silane treatment," "storage time," (p<0.0001), and their interaction were statistically significant (p<0.0010). Group means (MPa±SD), RCP (24 hours: 27.2±3.1; six months: 18.0±4.9), and HF-only control (24 hours: 21.1±3.4; six months: 15.7±5.8) showed a reduced bond strength after six months of water storage, while RCP + SB (24 hours: 23.4±4.4; six months: 22.2±5.4), SBU (24 hours: 18.8±3.0; six months: 17.2±3.6), and CP (24 hours: 21.7±4.3; six months: 17.4±4.8) remained constant. Weibull analysis revealed that more reliable bond strengths were obtained after six months for SBU and RCP + SB. Evaluation by scanning electron microscopy revealed that all groups demonstrated hydrolytic degradation at six months of storage, but RCP + SB and SBU indicated less. Use of a separate application of silane and adhesive system improved short and long-term ceramic/resin cement bond strength.

Effect of prior silane application on the bond strength of a universal adhesive to a lithium disilicate ceramic.

STATEMENT OF PROBLEM: Universal adhesives combine silane and various monomers in a single bottle to make them more versatile. Their adhesive performance is unclear. PURPOSE: The purpose of this in vitro study was to assess the effects of an additional silane application before using a universal adhesive on the adhesion between a disilicate glass ceramic and a composite resin by using a microshear bond strength test (µSBS) and fracture analysis immediately and after thermocycling. MATERIAL AND METHODS: One hundred lithium disilicate glass ceramic disks were divided into 10 groups for bond strength testing according to the following 3 surface treatments: silane application (built-in universal adhesive or with additional application), adhesive (Adper Single Bond Plus [SB, 3M ESPE], Scotchbond Universal Adhesive [U, 3M ESPE], and mixed U with Dual Cure Activator [DCA, 3M ESPE]); or thermocycling (half of the specimens were thermocycled 10000 times). After surface treatment, 5 resin cylinders were bonded to each disk and submitted to a µSBS test. The failure mode was analyzed under a stereomicroscope and evaluated by scanning electron microscope and energy-dispersive x-ray spectroscopy. Data from the µSBS test were analyzed by 3-way ANOVA followed by the Tukey HSD post hoc test (α=.05). RESULTS: An additional silane application resulted in a higher µSBS result for all adhesive groups (P<.05). CONCLUSIONS: Ceramic surface treatment influenced the performance of adhesives, which may be improved with an additional silane application.

Effect of a chlorhexidine/thymol and a fluoride varnish on caries development in erupting permanent molars: a comparative study.

AIM: To compare the caries preventive effect of a chlorhexidine/thymol-containing antibacterial varnish with a fluoride varnish when topically applied during the eruption of permanent molars. METHODS: The study group consisted of 189 patients, 5-14 years of age, with one 1st or 2nd permanent molar in the process of eruption. After stratification for type of molar and stage of eruption, the patients were randomised to either quarterly topical applications with an antibacterial varnish (Cervitec(®) Plus; CV group) or biannual applications with a fluoride varnish plus biannual treatments with placebo varnish (Fluor Protector; FV group). The duration of the study was 2 years. The primary endpoint was caries incidence (initial and cavitated) in the erupting molars and the secondary outcome was salivary mutans streptococci (MS) counts. RESULTS: The groups were balanced with respect to socio-economy, oral hygiene, dietary habits and caries experience at baseline. The dropout rate was 11.6 %. The caries incidence was low (< 10 %) in both groups and there was no significant difference between the CV and FV groups with respect to occlusal caries development in the erupting molars (relative risk 1.08, 95 % CI 0.94-1.25). Significantly lower levels of salivary MS were disclosed in the CV group at the end of the study (p < 0.05). CONCLUSIONS: No difference in occlusal caries development in young permanent molars was displayed after topical applications of either a chlorhexidine/thymol varnish or a fluoride varnish during tooth eruption.

The influence of varnish and high fluoride on erosion and abrasion in a laboratory investigation.

BACKGROUND: The aim of this study was to investigate the potential of concentrated fluoride varnishes to reduce enamel loss from repeated cycles of citric acid erosion and toothbrush abrasion in vitro. METHODS: Polished human enamel samples were exposed to fluoride varnishes: Bifluorid10® (NaF&CaF2- 45,200 ppmF), Duraphat® (NaF 22,600 ppmF), Fluor-Protector® (difluorsilane 1000 ppmF) and a control coating of copal ether varnish (0 ppmF) group and a deionized water group. For each group of 16 samples, nine cycles of erosion and nine cycles of erosion-abrasion [1 cycle=erosion (0.3% citric acid, pH 3.2, 5 min)+artificial saliva (1 h, pH 7.0)+abrasion (120 linear strokes in artificial saliva from Oral B medium soft brushes 300 g loading]. The change in the enamel surface was evaluated using optical profilometry. RESULTS: Duraphat® and Bifluorid10® applications had a median (IQR) step height of 4.21 um (1.59) and 5.01 um (1.02). This was statistically significantly less than Fluor-Protector® 6.83 um (1.25), copal ether 7.22 um (1.97) and water 7.39 um (1.96) (p<0.001). For erosion-abrasion, both Duraphat® and Bifluorid® had statistically lower step heights than the other products (p<0.01). CONCLUSIONS: The action of fluoride in a range of single-application topical varnishes was effective in reducing enamel wear from erosion and erosion-abrasion in this laboratory study.

Caries-preventive effectiveness of fluoride varnish as adjunct to oral health promotion and supervised tooth brushing in preschool children: a double-blind randomized controlled trial.

OBJECTIVES: To evaluate the effect of biannual fluoride varnish applications in preschool children as an adjunct to school-based oral health promotion and supervised tooth brushing with 1000ppm fluoride toothpaste. METHODS: 424 preschool children, 2-5 year of age, from 10 different pre schools in Athens were invited to this double-blind randomized controlled trial and 328 children completed the 2-year programme. All children received oral health education with hygiene instructions twice yearly and attended supervised tooth brushing once daily. The test group was treated with fluoride varnish (0.9% diflurosilane) biannually while the control group had placebo applications. The primary endpoints were caries prevalence and increment; secondary outcomes were gingival health, mutans streptococci growth and salivary buffer capacity. RESULTS: The groups were balanced at baseline and no significant differences in caries prevalence or increment were displayed between the groups after 1 and 2 years, respectively. There was a reduced number of new pre-cavitated enamel lesions during the second year of the study (p=0.05) but the decrease was not statistically significant. The secondary endpoints were unaffected by the varnish treatments. CONCLUSIONS: Under the present conditions, biannual fluoride varnish applications in preschool children did not show significant caries-preventive benefits when provided as an adjunct to school-based supervised tooth brushing with 1000ppm fluoride toothpaste. CLINICAL SIGNIFICANCE: In community based, caries prevention programmes, for high caries risk preschool children, a fluoride varnish may add little to caries prevention, when 1000ppm fluoride toothpaste is used daily.

Antibacterial effects of fluoride varnish compared with chlorhexidine plus fluoride in disabled children.

PURPOSE: To evaluate the effects of fluoride varnish vs a combination of chlorhexidine-thymol varnish plus a gel containing chlorhexidine and fluoride on oral hygiene and caries prevention in disabled children. MATERIALS AND METHODS: Ninety patients aged 3-17 years who were treated under general anaesthesia were randomly assigned into three groups as follows: group 1: Fluor Protector (0.1% fluoride varnish); group 2: Cervitec Plus (1% chlorhexidine- 1% thymol varnish) + Cervitec Gel (0.2% chlorhexidine-0.2% sodium fluoride); group 3: control (toothbrushing only). Mutans streptococci (MS) and lactobacilli (LB) levels, visible plaque index (VPI) and gingival bleeding index (GBI) were evaluated at four stages: T0, before general anaesthesia; T1, one month after treatment; T2, six months after treatment; T3, twelve months after treatment. The data were evaluated using Kruskal-Wallis and Mann-Whitney U-tests (P < 0.05). RESULTS: Groups 1 and 2 showed significantly lower scores than group 3 for all parameters at T1 and T2. No statistically significant difference was detected among any of the the groups at T3 (P > 0.05). CONCLUSION: The use of materials that include both fluoride and chlorhexidine as routine treatment of children with disability may increase the success of restorations by improving oral hygiene, reduce the need for future restorative treatments and thus the need for general anaesthesia.

Silylation improves the photodynamic activity of tetraphenylporphyrin derivatives in vitro and in vivo.

The effects of silyl and hydrophilic groups on the photodynamic properties of tetraphenylporphyrin (TPP) derivatives have been studied in vitro and in vivo. Silylation led to an improvement in the quantum yield of singlet oxygen sensitization for both sulfo and carboxy derivatives, although the silylation did not affect other photophysical properties. Silylation also improved the cellular uptake efficiency for both sulfo and carboxy derivatives, enhancing the in vitro photodynamic activity of the photosensitizer in U251 human glioma cells. The carboxy derivative (SiTPPC4 ) was found to show higher cellular uptake efficiency and in vitro photodynamic activity than the corresponding sulfo derivative (SiTPPS4 ), which indicates that the carboxy group is a more promising hydrophilic group than the sulfo group in the silylated porphyrin. SiTPPC4 was found to show high selective accumulation efficiency in tumors, although almost no tumor selectivity was observed for the nonsilylated porphyrin. The concentration of SiTPPC4 in tumors was 13 times higher than that in muscle 12 h after drug administration. We also studied tumor response after treatment and found that silylation enhanced in vivo photodynamic activity significantly. SiTPPC4 shows higher photodynamic activity than NPe6 with white light irradiation.

Prevention of enamel demineralization during orthodontic treatment: an in vitro comparative study.

AIM: Enamel demineralization is considered to be the most prevalent and significant iatrogenic effect associated with fixed orthodontic treatment and can seriously jeopardize both tooth longevity and dental esthetics. This in vitro study was undertaken to compare the effectiveness of four different commercially available surface treatment medicaments for the inhibition of enamel demineralization. METHODS: Seventy-five intact maxillary premolars extracted from patients undergoing orthodontic treatment were divided into five equal groups and were subjected to one of the following protocols: no treatment (control group) or treatment with one of the following four medicaments: fluoride varnish (Fluor Protector [FP]), casein phosphopeptide-amorphous calcium phosphate (GC Tooth Mousse [TM]), calcium sodium phosphosilicate (SHY-NM), and casein phosphopeptide-amorphous calcium phosphate with fluoride (GC Tooth Mousse Plus [TMP]). All the teeth were subjected to ten Cate demineralization solution?for 96 hours and subsequently evaluated under polarized light microscopy to obtain the mean depths of enamel demineralization. One-way analysis of variance and Bonferroni comparison tests were used to obtain statistically significant differences between the five different groups at P < .05. RESULTS: All four surface treatment medicaments provided statistically significant reduction in the depths of enamel demineralization as compared with the control group. FP provided the greatest protection of enamel surface in terms of reduction of lesion depth, followed by TMP, SHY-NM, and TM. CONCLUSIONS: The use of these commercially available medicaments could prove to be beneficial for patients undergoing orthodontic treatment and who are at a risk for developing enamel decalcification.

Recent progress of Shiga toxin neutralizer for treatment of infections by Shiga toxin-producing Escherichia coli.

Infection with Shiga toxin (Stx)-producing Escherichia coli (STEC), including O157:H7, causes bloody diarrhea and hemorrhagic colitis in humans, occasionally resulting in fatal systemic complications, such as neurological damage and hemolytic-uremic syndrome. Because Stx is a major virulence factor of the infectious disease, a series of Shiga toxin neutralizers with various structural characteristics has been developed as promising therapeutic agents. Most of these agents function to bind to the toxin directly and inhibit the binding to its receptor present on the target cells. Other neutralizers do not inhibit receptor binding but induce aberrant intracellular transport of the toxin, resulting in effective detoxification. Such a novel type of Stx neutralizer provides a new therapeutic strategy against STEC infections. Here, recent progress of the development of Stx neutralizers is reviewed.

Vascular protection and restorative therapy in ischemic stroke.

Possible strategies for treating stroke include: 1) thrombolytic therapy with tissue plasminogen activator (tPA): restoring cerebral blood flow in the acute phase of ischemic stroke but sometimes causing hemorrhagic transformation (HT); 2) stem cell therapy: the repair of disrupted neuronal networks with newly born neurons in the chronic phase of ischemic stroke. Firstly, we estimated the vascular protective effect of a free radical scavenger, edaravone, in the tPA-treated rat model of middle cerebral artery occlusion. Edaravone prevented dramatically decreased the hemorrhagic transformation and improved the neurologic score and survival rate of tPA-treated rats. Secondly, we attempted to restore brain tissue using a novel biomaterial, polydimethysiloxane-tetraethoxysilane (PDMS-TEOS) hybrid with or without vascular endothelial growth factor (VEGF), and we could show that implantation of a PDMS-TEOS scaffold with VEGF might be effective for treating old brain infarction or trauma. In the future, we will combine these strategies to develop more effective therapies for treatment of strokes.

Preventive effect of ozone on the development of white spot lesions during multibracket appliance therapy.

OBJECTIVE: To test the null hypotheses: (1) there is no difference in the caries protective effect of ozone and Cervitec/Fluor Protector during multibracket (MB) appliance therapy, and (2) DIAGNOdent and quantitative light-induced fluorescence (QLF) are not superior to a visual evaluation of initial caries lesions. MATERIALS AND METHODS: Twenty right-handed patients with a very poor oral hygiene who required full MB appliance therapy were analyzed during 26 months. In a split-mouth-design, the four quadrants of each patient were either treated with ozone, a combination of Cervitec and Fluor Protector, or served as untreated controls. The visible plaque index (VPI) and white spot formation were analyzed clinically. DIAGNOdent and QLF were used for a quantitative assessment of white spot formation. RESULTS: The average VPI in all four dental arch quadrants amounted to 55.6% and was independent of the preventive measure undertaken. In the quadrants treated with Cervitec/Fluor Protector, only 0.7% of the areas developed new, clinically visible white spots. This was significantly (P < .05) less than in the quadrants treated with ozone (3.2%). The lesions detected with QLF only partially corresponded to the clinically detected white spots, while DIAGNOdent proved to be unable to detect any changes at all. CONCLUSIONS: The caries protective effect of Cervitec/Fluor Protector during MB therapy was superior to ozone, and a visual evaluation of initial caries lesions was superior to both DIAGNOdent and QLF.

Inhibition of enamel demineralization by an enamel sealant, Pro Seal: an in-vitro study.

INTRODUCTION: Enamel demineralization adjacent to fixed orthodontic appliances compromises both esthetics and oral health. The purpose of this in-vitro study was to evaluate the effectiveness of a new enamel sealant, Pro Seal (Reliance Orthodontic Products, Itasca, Ill), on inhibiting enamel demineralization. Two materials that have demonstrated success in white spot prevention and do not require patient compliance were used for comparison. METHODS: Thirty-two noncarious extracted molars were divided into 4 groups and received 1 of the following treatments: no treatment (control), fluoride varnish (Fluor Protector; Ivoclar Vivadent, Amherst, Mass), unfilled resin sealant (Delton; Dentsply Professional, York, Pa), and filled resin sealant (Pro Seal). The teeth were subjected to 15,000 simulated brush strokes followed by acidic challenge for 96 hours. They were examined macroscopically and sectioned for quantitative examination with polarized light microscopy. RESULTS: All surface treatments provided statistically significant (P <.05) reductions in lesion depth compared with controls. Pro Seal performed significantly better (P <.05) than the other products, decreasing lesion depth by 97% compared with the controls and completely inhibiting lesion formation in 3 specimens. CONCLUSIONS: Pro Seal shows promise as an effective method of preventing enamel demineralization without patient compliance.

Effect of fluoride varnish on Streptococcus mutans counts in plaque of caries-free children using Dentocult SM strip mutans test: a randomized controlled triple blind study.

UNLABELLED: Dental caries is one of the most prevalent infectious diseases and although of multifactorial origin, Streptococcus mutans is considered the chief pathogen in its development. Fluoride is one of the most effective agents used for the reduction of dental caries apart from oral hygiene maintenance. AIMS: The aim of this study was to estimate the counts of Streptococcus mutans and to evaluate the effect of Fluor Protector fluoride varnish on these counts in the plaque of caries-free children using Dentocult SM Strip Mutans. MATERIALS AND METHODS: Thirty caries-free subjects were selected for the study based on the information obtained from a questionnaire and were randomly assigned to the control group consisting of ten subjects and the study group consisting of twenty subjects. Plaque samples were collected on the strips from the Dentocult SM kit and after incubation, the presence of Streptococcus mutans was evaluated using the manufacturer's chart. The study group was subjected to a Fluor Protector fluoride varnish application following which the samples were collected again after 24 hours. RESULTS: The average Streptococcus mutans counts in the primary dentition of caries-free children before and after the application of Fluor Protector fluoride varnish were 10(4)-10(5) colony forming units (CFU)/ml and <10(4) CFU/ml respectively. CONCLUSION: The results showed that the study group had a statistically significant reduction in the plaque Streptococcus mutans counts than the control group.

Effect of silanization on bond strengths of fiber posts to various resin cements.

OBJECTIVES: To investigate the effects of pretreatment (silanization) on bond strengths between 3 different types of fiber posts and 4 resin cements, respectively. METHOD AND MATERIALS: Prefabricated quartz-fiber (Unicore Post, Ultradent) and prefabricated glass-fiber (FRC Postec, Ivoclar Vivadent) posts with a cross-linked polymer matrix and individually formed glass-fiber posts with an interpenetrating polymer network (IPN Post, Stick Tech) (n = 160 each) were inserted into resin composite disks (2 mm thick) using the following resin cements and silane solutions: Panavia F/Porcelain Bond Activator (Kuraray), PermaFlo DC/Silane (Ultradent), Variolink II/Monobond S (Ivoclar Vivadent) and RelyX Unicem/Espe Sil (3M Espe). Nonsilanated posts served as controls. The push-out bond strengths were determined before (n = 10) and after (n = 10) thermocycling (2,000 cycles, 5 degrees C to 55 degrees C, dwelling time 30 seconds). RESULTS: Bond strengths (mean [SD]) were significantly affected by the resin cement (P < .001), the pretreatment (P < .001), and the type of post (P < .001), but not by thermocycling (P = .955, 4-way ANOVA). The IPN post demonstrated significantly higher bond strengths compared to the other posts (P < .05; Tukey B). Silanization significantly increased bond strengths (15.2 [5.2] MPa) compared to those of the control groups (13.9 [4.9] MPa). CONCLUSION: The type of fiber post revealed a significant influence on bond strengths, whereas the effects of silanization appeared to be clinically negligible.

Microleakage of Ormocer-based restorative material in primary teeth: an in vivo study.

This in vivo study aimed to compare, by means of dye penetration, the microleakage values of an Ormocer-based material (Admira) and a commonly-used composite resin (Restorative Z-100) and to assess the differences in the degree of microleakage according to the cavity wall location for both tested materials. No statistically significant differences were found in the degree of microleakage between the 2 materials or the location of cavity walls. Additional preventive measures should be considered to minimize leakage since none of the restorative systems used, eliminated microleakage.

Vascular endothelial growth factor promotes brain tissue regeneration with a novel biomaterial polydimethylsiloxane-tetraethoxysilane.

In the brain after infarction or trauma, the tissue eventually becomes pannecrotic and forms a cavity. In such situations, a scaffold is necessary for the implanted or migrated cells to produce new tissue. In this present study, therefore, we attempted to restore brain tissue using a novel biomaterial, polydimethylsiloxane-tetraethoxysilane (PDMS-TEOS) hybrid with or without vascular endothelial growth factor (VEGF), which is crucial for new vessel formation. When PDMS-TEOS scaffold was implanted into the artificial brain defect, it remained at the implanted site and kept the integrity of the brain shape. At 30 days after the implantation, the marginal territory of PDMS-TEOS scaffold became occupied by newly formed tissue. Immunohistochemical analysis revealed that the new tissue was constituted by astrocytes and endothelial cells. Addition of VEGF increased the newly produced tissue volume, and the immunohistochemical analysis showed that the numbers of astrocytes and endothelial cells were increased. Double staining with proliferation maker Ki67 demonstrated that VEGF significantly increased newly formed astrocytes and endothelial cells, indicating that addition of VEGF accelerated tissue restoration and angiogenesis. These findings show that implantation of PDMS-TEOS scaffold with VEGF might be effective for treating old brain infarction or trauma.