Cisplatin-loaded mesoporous polydopamine nanoparticles capped with MnO2 and coated with platelet membrane provide synergistic anti-tumor therapy.

A multifunctional nanoplatform was constructed in this work, with the goal of ameliorating the challenges faced with traditional cancer chemotherapy. Cisplatin (CP) was loaded into mesoporous polydopamine (mPDA) nanoparticles (NPs) with a drug loading of 15.8 ± 0.1 %, and MnO2 used as pore sealing agent. Finally, the NPs were wrapped with platelet membrane (PLTM). P-selectin on the PLTM can bind to CD44, which is highly expressed on the tumor cell membrane, so as to improve the targeting performance of the NPs. In addition, the CD47 on the PLTM can prevent the NPs from being phagocytosed by macrophages, which is conducive to immune escape. The final PLTM-CP@mPDA/MnO2 NPs were found to have a particle size of approximately 198 nm. MnO2 is degraded into Mn2+ in the tumor microenvironment, leading to CP release from the pores in the mPDA. CP both acts as a chemotherapy agent and can also increase the concentration of H2O2 in cells. Mn2+ can catalyze the conversion of H2O2 to OH, resulting in oxidative damage and chemodynamic therapy. In addition, Mn2+ can be used as a contrast agent in magnetic resonance imaging (MRI). In vitro and in vivo experiments were performed to explore the therapeutic effect of the NPs. When the concentration of CP is 30 µg/mL, the NPs cause approximately 50 % cell death. It was found that the PLTM-CP@mPDA/MnO2 NPs are targeted to cancerous cells, and in the tumor site cause extensive apoptosis. Tumor growth is thereby repressed. No negative off-target side effects were noted. MRI could be used to confirm the presence of the NPs in the tumor site. Overall, the nano-platform developed here provides cooperative chemotherapy and chemodynamic therapy, and can potentially be used for effective cancer treatment which could be monitored by MRI.

HPMC films functionalized by zein/carboxymethyl tamarind gum stabilized Pickering emulsions: Influence of carboxymethylation degree.

Pickering emulsions are promising systems to act as carriers of active hydrophobic components, and to improve compatibility and the water vapor barrier properties of bio-based films. This study aimed to investigated the effects of cinnamon essential oil Pickering emulsions (CEOEs) using zein/carboxymethyl tamarind gum as stabilizers on the mechanical, barrier, antibacterial and antioxidant properties of Hydroxypropyl methyl cellulose (HPMC) films, and assessed the influence of carboxymethylation degree. In addition, the effect of the packaging was studied on the shelf life of cherry tomatoes. Results showed that the droplet size reduced approximately from 93.03 to 10.59 µm with the increasing degree of substitution (DS), greatly facilitating the droplet uniform distribution in film matrix. Moreover, with the addition of CEOEs, significant increase was observed with the tensile strength from 8.46 to 25.41 MPa, and the water vapor permeability decreased from 6.18 × 10-10 to 4.24 × 10-10 g·m-1·s-1·Pa-1. The films exhibited good UV barrier properties without sacrificing the transparency after adding CEO. Furthermore, the antibacterial and antioxidant activities of the prepared films have also been greatly improved. Consequently, the CEOEs was an ideal alternative for incorporation with HPMC based films for increasing the shelf life of cherry tomatoes.

Sodium Fluoride and Sulfur Dioxide Derivatives Induce TGF-ß1-Mediated NBCe1 Downregulation Causing Acid-Base Disorder of LS8 Cells.

The aim of the present work was to assess whether the combination of sodium fluoride (NaF) and sulfur dioxide derivatives (SO2 derivatives) affects the expression of the electrogenic sodium bicarbonate cotransporter NBCe1 (SLC4A4), triggering an acid-base imbalance during enamel development, leading to enamel damage. LS8 cells was taken as the research objects and fluorescent probes, quantitative real-time polymerase chain reaction (qRT-PCR), western blot, and factorial analysis were used to clarify the nature of the fluoro-sulfur interaction and the potential signaling pathway involved in the regulation of NBCe1. The results showed that exposure to fluoride or SO2 derivatives resulted in an acid-base imbalance, and these changes were accompanied by inhibited expression of NBCe1 and TGF-ß1; these effects were more significant after fluoride exposure as compared to exposure to SO2 derivatives. Interestingly, in most cases, the toxic effects during combined exposure were significantly reduced compared to the effects observed with fluoride or sulfur dioxide derivatives alone. The results also indicated that activation of TGF-ß1 signaling significantly upregulated the expression of NBCe1, and this effect was suppressed after the Smad, ERK, and JNK signals were blocked. Furthermore, fluoride and SO2 derivative-dependent NBCe1 regulation was found to require TGF-ß1. In conclusion, this study indicates that the combined effect of fluorine and sulfur on LS8 cells is mainly antagonistic. TGF-ß1 may regulate NBCe1 and may participate in the occurrence of dental fluorosis through the classic TGF-ß1/Smad pathway and the unconventional ERK and JNK pathways.

Improving the valence self-reversible conversion of cerium nanoparticles on titanium implants by lanthanum doping to enhance ROS elimination and osteogenesis.

Equipped with anti-oxidative properties, cerium oxide nanoparticles (CNPs) are gradually being adopted over the years in the field of oxidative stress research. However, the effects of CNPs may be diminished when under the influence of prolonged and substantially elevated levels of oxidative stress. Therefore, it is imperative to enhance the efficacy of CNPs to resist oxidative stress. In this study, our approach involves the fabrication of titanium surface CNPs coatings doped with different concentrations of lanthanum ions (La3+) and the investigation of their local anti-oxidative stress potential. The physicochemical characterization showed that the La-CNPs groups had a substantial increase in the generation of oxygen vacancies within the CNPs structure with the increase of La doping concentration. In vitro findings proofed that the cytocompatibility of different La-CNPs coatings showed a trend of increasing first and then decreasing with the increase of La doping concentration under oxidative stress microenvironment. Among these groups, the 30 % La-CNPs group presented the best cell proliferation and osteogenic differentiation which could activate the FoxO1 pathway, then upregulated the expression of SOD1 and CAT, and finally resulted in the inhibition of ROS production. In vivo results further confirmed that the 30 % La-CNPs group showed significant osteogenic effects in two rat models (osteoporosis and diabetes models). In conclusion, we believe that the 30 % La-CNPs coating holds promising potential for its implant applications in patients with oxidative stress-related diseases.

Multifunctional TaCu-nanotubes coated titanium for enhanced bacteriostatic, angiogenic and osteogenic properties.

In this study, multifunctional tantalum copper composite nanotubes (TaCu-NTs) were coated on titanium for enhanced bacteriostatic, angiogenic and osteogenic properties. Three coatings of Ta, TaCu1 (Ta: Cu = 4:1 at.%), and TaCu2 (Ta: Cu = 1:1 at.%) were deposited on titanium by magnetron sputtering. The bare titanium and the three coatings were subsequently anodized into four kinds of nanotubes (NT) of TNT, Ta-NT, TaCu1-NT, and TaCu2-NT, respectively. The released copper ions measured by inductively coupled plasma atomic emission spectroscopy (ICP/AES) presented that TaCu2-NT coating released the highest amount of copper ions, which led to the best bacteriostasis against Escherichia coli and Staphylococcus aureus. Potentiodynamic polarization tests clarified that Ta-NT showed the highest corrosion resistance, followed by TaCu1-NT and TaCu2-NT. TaCu2-NT showed not only the best angiogenic property in terms of cell migration, tube formation, and real-time quantitative polymerase chain reaction (RT-qPCR) of human umbilical vein endothelial cells (HUVECs), but also the best osteogenic property in terms of cell viability, alkaline phosphatase activity, and mineralization of MC3T3-E1 cells. Therefore, TaCu2-NT coating has a greater potential than the other coatings of TNT, Ta-NT and TaCu1-NT in promoting bacteriostasis, angiogenesis and osteointegration for titanium implants.

JK-2 loaded electrospun membrane for promoting bone regeneration.

Hydrogen sulfide (H2S) has been as an essential gasotransmitter and a potential therapeutic approach for several biomedical treatments such as cardiovascular disorders, hypertension, and other diseases. The endogenous and exogenous H2S also plays a crucial role in the bone anabolic process and a protective mechanism in cell signalling. In this study, we have utilized two types of polymers, polycaprolactone (PCL) and gelatin (Gel), for the fabrication of JK-2 (H2S donor) loaded nanofibrous scaffold via electrospinning process for bone healing and bone tissue engineering. Comparing the PCL/Gel and PCL/Gel-JK-2 scaffolds, the latter demonstrated enhanced cell adhesion and proliferation capabilities. Furthermore, both experimental scaffolds have been subjected to an in vivo experiment for 4 and 8 weeks in a bone-defect model of a rabbit to determine their biological responses under physiological conditions. There was an obvious increase in bone regeneration in the PCL/Gel-JK-2 group compared to the control and PCL/Gel groups. These results indicate the use of PCL/Gel scaffolds loaded with JK-2 should be considered for possible bone regeneration.

Bioactive nanocomposite coatings under visible light illumination promoted surface-mediated gene delivery.

Gene delivery based on bioactive coatings on collagen has great potential for applications in bone repair. Meanwhile, controlled gene delivery at specific times/regions is essential for an efficient and complete bone reconstruction process. However, spatio-temporal regulation of gene release and delivery remains a great challenge. In this paper, we used visible light illumination to effectively regulate gene release and subsequent delivery into biological cells. A visible light responsive and bioactive nanocomposite coating (based on collagen/gold nanoparticles, e.g., Col/AuNPs) was prepared through hydrothermal and sol-gel processes and was used as a loading platform for complexes of enhanced green fluorescent protein and Lipofectamine2000 (LF/GFP). The results showed that the amount of immobilized LF/GFP was increased on Col/AuNPs and the release of pre-adsorbed LF/GFP was significantly enhanced in a spatio-temporal and controlled manner under visible light illumination. Moreover, the cellular intake of the released genes was improved, thus enhancing the gene expression efficiency of the cells. The mechanism of enhanced controlled gene delivery was attributed to the changes in collagen structures and rearrangement of cytoskeletal structures induced by the photothermal effect. The developed Col/AuNP composite coating is effective for both controlled surface-mediated gene delivery and gene-mediated bone repair.

Antibacterial and Osteogenic Functionalization of Titanium With Silicon/Copper-Doped High-Energy Shot Peening-Assisted Micro-Arc Oxidation Technique.

Antibacterial and osteogenic functionalization of titanium (Ti) implants will greatly expand their clinical indications in immediate implant therapy, accelerate osteointegration, and enhance long-term prognosis. We had recently shown that the high-energy shot peening (HESP)-assisted micro-arc oxidation (MAO) significantly improved the bioactivity and coating stability of Ti-based substrates. In this study, we further functionalized Ti with antibacterial and osteogenic properties by doping silicon (Si) and/or copper (Cu) ions into HESP/MAO-treated coatings. Physicochemical characterization displayed that the doping of Si and Cu in HESP/MAO-treated coatings (Si/Cu-MAO) did not significantly change their surface topography, roughness, crystal structure, coating thickness, bonding strength, and wettability. The results of X-ray photoelectron spectroscopy (XPS) showed that Si and Cu in the Si/Cu-MAO coating was in the form of silicate radical (SiO3 2-) and bivalent copper (Cu2+), respectively. The total amounts of Si and Cu were about 13.5 and 5.8 µg/cm2, which released about 33.2 and 31.3% within 14 day, respectively. Compared with the control group (MAO), Si doping samples (MAO-Si) significantly increased the cell viability, alkaline phosphatase (ALP) activity, mineralization and osteogenic genes (ALP, collagen I and osteocalcin) expression of MC3T3-E1 cells. Furthermore, the addition of Cu presented good bactericidal property against both Staphylococcus aureus and Streptococcus mutans (even under the co-culture condition of bacteria and MC3T3-E1 cells): the bacteriostatic rate of both bacteria was over 95%. In conclusion, the novel bioactive Si/Cu-MAO coating with antibacterial and osteogenic properties is a promising functionalization method for orthopedic and dental implants, especially in the immediate implant treatment with an infected socket.

Electrical Potential Specified Release of BSA/Hep/Polypyrrole Composite Film and Its Cellular Responses.

A facile strategy is needed for accurate time-space supply of suitable growth factors or drugs. Polypyrrole (PPy) was able to carry almost all kinds of negatively charged biomolecules through anodizing method, which made it an appropriate way for codeposition of multiple molecules. The difference in the conjugation between different molecules and PPy makes it possible for selective release when the redox state of PPy changes. In this work, bovine serum albumin (BSA) and heparin (Hep) were chosen to be the model molecules in view of their differences in the level of electronegativity and molecular weight. Double-layer deposition method was used to improve the biocompatibility of PPy/BSA/Hep film. It was found the content of BSA and Hep in the film can be controlled by regulating deposition current and time. BSA release was facilitated under positive voltage and then promote the proliferation of preosteoblasts, while Hep release was promoted under negative voltage and enhance cell differentiation. Our work provides a dual-molecule model in PPy for selective release and further explores the mechanism of release selectivity, this discovery has potential applications in tissue engineering and regenerative medicine.

Graphene/Si-Promoted Osteogenic Differentiation of BMSCs through Light Illumination.

Graphene (Gr) presents promising applications in regulating the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). Light illumination is regarded as a spatiotemporally controllable, easily applicable, and noninvasive mean to modulate material responses. Herein, Gr-transferred silicon (Gr/Si) with a Schottky junction is utilized to evaluate the visible-light-promoted osteogenic differentiation of BMSCs. Under light illumination, light-induced charges, owing to the formation of the Schottky junction at the interface of Gr and Si, accumulated on the surface and then changed the surface potential of Gr/Si. The Schottky junction and surface potential at the interface of Gr and Si was measured by photovoltaic test and scanning Kelvin probe microscopy. Alkaline phosphatase (ALP) activity and quantitative real-time polymerase chain reaction (PCR) measurement showed that such variations of surface improved the osteogenic differentiation of BMSCs, and the activation of the voltage-gated calcium channels through surface potential and accumulation of cytosolic Ca2+ could be the reason. Moreover, X-ray photoelectron spectroscopy characterization showed that surface charge could also affect BMSCs differentiation through the promotion or inhibition of the adsorption of osteogenic growth factors. Such light-promoted osteogenic differentiation of BMSCs on Gr/Si may have huge potential for biomedical materials or devices for bone regeneration application.

[Comparison of the effect of three nickel-titanium instruments on molar root canal curvature].

PURPOSE: To evaluate the influence of ProTaper, Mtwo, and M3 nickel-titanium instruments on root canal curvature during root canal preparation. METHODS: Forty-five molars with root canal therapy were randomly divided into 3 groups. The root canals were prepared by using ProTaper, Mtwo and M3 nickel-titanium instruments. The qualified rate and change of root canal curvature before and after preparation were compared using SPSS22.0 software package. RESULTS: There was no significant difference between the three groups in the qualification rate after root canal preparation and the effect of different preparatory devices on root canal curvature(P>0.05), but there was significant difference in the change of root canal curvature before and after preparation (P<0.05). CONCLUSIONS: The three kinds of nickel-titanium instruments can effectively form root canal and have no difference in root canal curvature， but the curvature of root canal is changed after preparation. It is important to prevent complications during curved root canal preparation.

[Comparison of clinical efficacy of CAD/CAM all -ceramic inlay and polymerid porcelain inlay in restoration of posterior Class II cavity].

PURPOSE: To compare the clinical efficacy of CAD/CAM all-ceramic inlay and polymerid porcelain inlay in restoring Class II cavity of posterior teeth. METHODS: Ninety-seven patients with 100 posterior teeth of ClassII cavity were recruited in this randomized control trial; Among them, 50 patients were grouped into CAD/CAM all-ceramic inlays and 47 patients were grouped into Ceramage polymerid porcelain inlay. According to the modified USPHS criteria, the incidence of postoperative sensitivity, prosthesis fracture, prosthesis falling off, and edge coloration were evaluated 12 months and 24 months after restoration. Chi-square test and Wilcoxon rank sum test were used for statistical analysis using SPSS 13.0 software package. RESULTS: Restoration in the 2 groups were successful, there was no significant difference at 12 months (P>0.05). Postoperative sensitivity and the incidence of prosthesis falling off in both groups were not significantly different (P>0.05); however, the number of prosthesis fracture of the polymerid porcelain was lower than that of the CAD/CAM all-ceramic inlays (P<0.05). The incidence of edge coloration of CAD/CAM all-ceramic inlays was lower than that of the polymerid porcelain at 24-month follow-up (P<0.05). CONCLUSIONS: Restoration with polymerid porcelain is more likely to have a higher success rate than those with CAD/CAM all-ceramic inlays. Patients undergoing CAD/CAM all-ceramic inlays have a lower incidence of edge coloration, compared with those undergoing polymerid porcelain.

[Influence of age on the effectiveness of revascularization in immature permanent teeth].

PURPOSE: To evaluate the effect of age on the potential of dental pulp regeneration in young permanent teeth with periapical periodontitis. METHODS: A total of 30 mandibular premolars from 9-18 years old patients with pulp necrosis were divided into 2 groups, group A (younger age group): 9-13 years old, and group B (older age group): 14-18 years old. Revascularization procedures were performed for all patients. Follow-up was done for up to 18 months. Standardized radiographs of cone-beam CT (CBCT) were digitally evaluated for increase in root length and thickness. The data were analyzed by nonparametric two sample rank sum test using SPSS13.0 software package. RESULTS: After 18 months of follow-up, the clinical symptoms of the two groups disappeared. The cure rate of group A was significantly higher than that of group B (P=0.003). Radiographic analysis showed that the root length and root canal wall thickness in group A was significantly greater than those in group B (P<0.05). CONCLUSIONS: Root canal revascularization can be widely used in the treatment of dental pulp necrosis in young permanent teeth. The closer the age is to the eruption time, the higher the potential of dental pulp regeneration, and the more suitable for root canal revascularization.

[Evaluation of the use of dental operating microscope in the management of blocked canals].

PURPOSE: This study was performed to evaluate the value of dental operating microscope(DOM) in treating blocked canals. METHODS: 161 blocked canals in 113 teeth were treated with ultrasonic instruments under DOM. The etiology of canal blockage included calcification, resinifying therapy and broken instruments. All canals were grouped based on the cause of blockage, teeth site and blockage location in canals, and then the success rates of negotiating ,using SPSS10.0 software package, were analyzed with X(2) test. RESULTS: The results showed that 131 canals were negotiated with a success rate of 81.37%.Blocked canals caused by calcification, resinifying therapy and broken instruments were managed with the success rate of 84.27%, 81.58% and 73.53%, respectively.There were no significant differences in the success rate(P>0.05). Blocked canals of anterior were managed successfully with a success rate of 93.48%,canals of premolar with a success rate of 84.61%,and canals of molar with a success rate of 72.37%. There were significant differences in the success rate between anterior and molar teeth(P<0.01).When the blockage was located in straight canals or above the root canal curvature,canals were negotiated with a success rate of 93.98>.However,the success rate decreased to 21.42> when the blockage located below the root canal curvature,and significant differences were found(P<0.01). CONCLUSIONS: It is an effective way to use dental operating microscope to treat blocked canals, but the therapeutic effects might be affected by sites of the teeth and the blockage location in canals.

[Evaluation of the clinical effect of the teeth with subgingivally involved defect conserved by crown lengthening surgery].

PURPOSE: To evaluate the clinical effect of the teeth with subgingivally involved defect which were conserved by crown lengthening surgery. METHODS: 62 teeth, with defect subgingivally from 1.5 mm to 4 mm, mobility degree(MD)0.05), but a significant increase about MD occurred in the major defect group one year after restoration (P<0.01), and there was significant correlation between MD of each stage after operation and PD of pre-operation in anterior teeth (r=0.489, 0.526, 0.531, P<0.01). CONCLUSIONS: According to the biological width principle, crown lengthening surgery may conserve these teeth with subgingivally involved defect, and has a good, long-time clinical effect. But MD showed an increasing trend after operation and significant cor.