Three-Dimensional Printed Poly (Lactic-co-Glycolic Acid)-Magnesium Composite Scaffolds for the Promotion of Osteogenesis Through Immunoregulation.

Scaffolds play an important role in bone tissue engineering. The ideal engineered scaffold needs to be biocompatible, bioactive, and able to regulate immune cells to enhance bone regeneration. In this study, magnesium (Mg)-contained poly(lactic-co-glycolic acid) (PLGA) scaffolds (hereinafter, referred to as PLGA-2Mg) were fabricated by 3-dimensional printing using a mixture of PLGA and MgSO 4 powder. Poly(lactic-co-glycolic acid) scaffolds (hereinafter, referred to as PLGA) were also fabricated by 3-dimensional printing and were used as control. The biocompatibility, immunoregulatory ability, and osteogenic properties of PLGA-2Mg were analyzed and compared with those of PLGA. The results indicate that the incorporation of Mg increased the Young modulus and surface roughness of the scaffold, but did not affect its degradation. The PLGA-2Mg further promoted the adhesion and proliferation of MC3T3-E1 cells compared with PLGA, which indicates its improved biocompatibility and bioactivity. In addition, PLGA-2Mg inhibited the polarization of RAW 264.7 cells toward the M1 phenotype by down-regulating the IL-1ß , IL-6 , and iNOs gene expression when challenged with lipopolysaccharide stimulation. In contrast, it promoted the polarization of RAW 264.7 cells toward the M2 phenotype by up-regulating the TGF-ß , IL-10 , and Arg-1 gene expression without lipopolysaccharide stimulation. Finally, MC3T3-E1 cells were cocultured with RAW 264.7 cells and scaffolds using a transwell system. It was found that the expression level of osteogenic-related genes ( ALP , COL-1 , BMP2 , and BSP ) was significantly upregulated in the PLGA-2Mg group compared with that in the PLGA group. Consequently, PLGA-2Mg with increased biocompatibility and bioactivity can promote osteogenesis through immunoregulation and has the potential to be used as a novel scaffold in bone tissue engineering.

Efficient and Regioselectivity-Tunable Metal-Free Polycycloaddition of Activated Azide and Alkynes.

The transition-metal catalyzed and metal-free click polymerizations have been developed as powerful tools for the construction of functional polymers with linear and hyperbranched structures. The latter provides a thorough solution for the completely removing metallic residues from the products encountered in the former. Compared to the activated alkyne-azide metal-free click polymerization, the activated azide-alkyne one is rarely studied. In this Communication, a perfluorophenyl-activated azide of hexane-1,6-diyl-bis(4-azido-2,3,5,6-tetrafluorobenzoate) is rationally designed and facilely prepared. Through systematical optimization of the reaction conditions, an efficient metal-free perfluorophenylazide-alkyne polycycloaddition is established, and polytriazoles with high molecular weights (up to 166 000) and excellent solubility are obtained in excellent yields (up to 93%) under mild reaction conditions. Interestingly, the regioselectivity of the reaction could be fine-tuned by the solvents and diyne monomers. Therefore, this work provides not only a powerful tool for the preparation of functional polytriazoles, but also an attractive method for fine-tuning their regioregularity.

A visual and organic vapor sensitive photonic crystal sensor consisting of polymer-infiltrated SiO2 inverse opal.

A photonic crystal (PC) sensor that can selectively detect organic vapors through visual color changes has been proposed. The sensor was fabricated by infiltrating a tetraphenylethene polymer (TPEP) into the voids of SiO2 inverse opal photonic crystal. When the sensor was exposed to tetrahydrofuran or acetone vapor, a red shift of the stopband of more than 50 nm could be clearly observed; meanwhile, the film's color changed from violet to cyan. Subsequently, when exposed to air, the stopband underwent a blue shift and the color returned to violet. The reason for the observed change is that a reversible adsorption-desorption process occurs on alternate exposure of the sensor to organic vapor and air, due to the high specific surface area of the inverse opal macroporous structure and the high affinity of TPEP to tetrahydrofuran and acetone. The adsorption of vapor analyte can increase the PC's effective refractive index, which will induce the stopband red shift and the resulting color change according to Bragg's Law. The reversible adsorption-desorption of organic vapors varied the effective refractive index of the sensor repeatedly, causing the reversible stopband shift and color change, and providing a general method for the design of visual vapor sensors.

Aggregation-induced emission of tetraphenylethene-hexaphenylbenzene adducts: effects of twisting amplitude and steric hindrance on light emission of nonplanar fluorogens.

A series of nonplanar tetraphenylethene (TPE)-hexaphenylbenzene (HPB) adducts was designed and synthesized by Diels-Alder reaction of the acetylene precursors and tetraphenylcyclopentadienone. All of the adducts showed aggregation-induced emission features. The twisting amplitude and steric hindrance of the TPE and HPB units were found to play a crucial role in their fluorescence behaviors in the aggregated state.

Ordered honeycomb structural interfaces for anticancer cells growth.

The patterned honeycomb structure film with the aggregation-induced emission property was prepared successfully by the breath figure method and photopolymerization method. Characterization of the HeLa and HepG2 cell culture on this surface indicates the porous honeycomb structures show anticancer cells growth function. So this kind of honeycomb structure will be promising for the control of cancer cell growth behaviors and achieving the application of anticancer.

Effect of the alumina micro-particle sizes on the thermal conductivity and dynamic mechanical property of epoxy resin.

Epoxy thermal conductive adhesives with high thermal conductivity and dynamic mechanical properties are important thermally conductive materials for fabricating highly integrated electronic devices. In this paper, micro-Al2O3 is used as a thermally conductive filler for the epoxy resin composite and investigated the effect of micron-sized alumina particle size on the thermal conductivity and dynamic mechanical property of epoxy resin by the transient planar hot plate method and DMA (Dynamic mechanical analysis). The experimental results show that with the same amount of alumina filling, the thermal conductivity and Tg (glass transition temperature) of epoxy/Al2O3 composite material decrease with the increase of alumina particle size. The maximum thermal conductivity of the composite material is 0.679 (W/mK), while the energy storage modulus of epoxy/Al2O3 composite material increases with the increase of alumina particle size, and the maximum energy storage modulus of the composite material is 160MPa. Compared with pure epoxy resin, the thermal conductivity and energy storage modulus have increased by 2.7 and 3.2 times, respectively. The epoxy/Al2O3 composite was applied to the COB (Chips On Board) type LED package, and the substrate temperature of the LED dropped to the lowest after 1.5 hours of operation using EP-A5 composite, and the temperature was stabilized at 38.2°C, indicating that the addition of 5-micron alumina composite has the best heat dissipation in the COB type LED package. These results are critical for the implementation of particulate-filled polymer composites in practical applications because relaxed material specifications and handling procedures can be incorporated in production environments to improve efficiency.

Conjugated hyperbranched poly(aryleneethynylene)s: synthesis, photophysical properties, superquenching by explosive, photopatternability, and tunable high refractive indices.

Triphenylamine (TPA)-based conjugated hyperbranched poly(aryleneethynylene)s (PAEs), hb-P1/2, hb-P1/3, and hb-P1/4, were synthesized with high molecular weights and good solubilities through Sonogashira coupling reactions. These PAEs exhibited outstanding thermal stabilities and different emission behaviors. Tetraphenylethene (TPE)-containing hb-P1/2 fluoresced faintly in THF, although its light emission was enhanced by aggregate formation in aqueous media or in thin films, thereby exhibiting an aggregation-induced emission-enhancement (AIEE) effect. Whereas 1,1,2,3,4,5-hexaphenylsilole (HPS)-bearing hb-P1/3 showed no significant change in emission intensity with increasing water content in aqueous media, hb-P1/4, which consisted of TPA-fluorenone donor-acceptor groups, presented almost identical absorptions, but both positive and negative solvatochromic emissions in various solvents. A superquenching effect was observed in the picric-acid-detection process by using nanosuspensions of hb-P1/2. All of the polymers possessed good film formability. UV irradiation of the thin films induced simultaneous photobleaching and cross-linking, thus making them applicable in the fabrication of 2D and 3D patterns. Furthermore, the polymer films also showed high refractive indices, which were tunable upon exposure to UV light.

[Effect of phospholipid composition on pharmaceutical properties and anti-tumor activity of stealth liposomes containing brucine].

OBJECTIVE: To compare the pharmaceutical properties and the anti-tumor activities of three kinds of stealth liposomes prepared with different phospholipid composition containing brucine. METHOD: Stealth liposomes with different phospholipids composition, such as soybean phosphatidycholine (SPC), hydrogenated soybean phosphatidylcholine (HSPC) and the complex of SPC and HSPC, were prepared by ammonium sulfate transmembrane gradient method. Pharmaceutical properties such as shape, encapsulation efficiency and size of three stealth liposomes were compared intensively. Anti-tumor activity of SPC, HSPC and novel stealth liposomes composed of both SPC and HSPC were compared by established mouse liver cancer H22 model. Meanwhile, the mice body weight and immune organ weight were also compared. RESULT: The encapsulation efficiency of novel, SPC and HSPC stealth liposomes were 77.7%, 64.8% and 74.8%, respectively. The mean diameters of them were less than 100 nm. The tumor inhibition rate of novel, HSPC and SPC stealth liposomes were 57.88%, 49.15%, 23.37%, respectively. The mice body weight, thymus gland index of three stealth liposomes group and spleen index of novel stealth liposomes group had no significant difference with the negative group while SPC and HSPC stealth liposomes group increased the spleen index. CONCLUSION: Phospholipids composition is the key factor which determines the antitumor activity of brucine-loaded stealth liposomes.

The suppressive effects of miR-508-5p on the odontogenic differentiation of human dental pulp stem cells by targeting glycoprotein non-metastatic melanomal protein B.

BACKGROUND: Although the involvement of glycoprotein non-metastatic melanomal protein B (GPNMB) in regulating the odontogenic differentiation of human dental pulp stem cells (hDPCs) has been identified, the underlying mechanisms are largely unknown. The purpose of this study is to investigate the effects of miR-508-5p on the GPNMB expression and the odontogenic differentiation of hDPCs. METHODS: In this study, hDPCs were isolated and identified by flow cytometric analysis. Based on bioinformatics analysis, dual luciferase reporter assay was performed to verify GPNMB acting as a target of miR-508-5p. The regulatory roles of miR-508-5p in odontogenetic differentiation of hDPCs were investigated through its inhibition or overexpression (miRNA mimics and miRNA inhibitors). qRT-PCR and Western blot analysis were used to detect the expression of odontogenetic marker genes and proteins. The assays of alkaline phosphatase (ALP) activity and Alizarin Red S staining were performed to evaluate the odontogenetic phenotype. RESULTS: We first found that the levels of miR-508-5p expression decreased gradually during odontogenesis of hDPCs, while the expressions of GPNMB were upregulated obviously. The suppressive effects of miR-508-5p on GPNMB were determined by oligonucleotide transfection in hDPCs and dual luciferase reporter assay in 293T cells. Subsequently, the significant inhibition of hDPC odontogenesis after the overexpression of miR-508-5p was observed, which is consistent with the decreased expression levels of several odontoblast-specific genes, such as dentin matrix protein 1 (DMP-1), dentin sialophosphoprotein (DSPP), and osteocalcin (OCN), as well as the decreased activity of ALP and weakened Alizarin Red S staining. Furthermore, ectopic expression of GPNMB (lacking 3'-UTR) rescued the effects of miR-508-5p on odontogenic differentiation. CONCLUSIONS: Our study demonstrated that miR-508-5p regulated the osteogenesis of hDPCs by targeting GPNMB and provided novel insight into the critical roles of microRNAs in hDPC differentiation.

Effects and complications of placement of motility coupling post in porous polyethylene orbital implants.

OBJECTIVE: To investigate the effects and complications of primary and secondary placements of motility coupling post (MCP) in the unwrapped porous polyethylene orbital implant (PPOI) following enucleation. METHODS: We investigated 198 patients who received PPOI implantation following the standard enucleation procedure in the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China, from 2002 to 2004. These patients were subgrouped into PPOI-only patients (112 cases, received PPOI following enucleation), primary MCP patients (46 cases, received primary placement of MCP during PPOI operation), and secondary MCP patients (40 cases, received secondary placement of MCP 6 months after the initial surgery). Effects and complications among these three groups were compared. RESULTS: The PPOI-only patients took shorter treatment course when compared with other two MCP groups (P<0.001), without significant difference noted between the two MCP groups. However, the two MCP groups had better prosthetic motility than PPOI-only group (P<0.001), without significant difference between the two MCP groups. In the early stage, 2 eyes in the PPOI-only group and 1 eye in the primary MCP group had PPOI infection. In PPOI-only group, 3 (2.68%) eyes had PPOI exposure, which occurred after fitting the prostheses; 4 eyes (8.70%) in primary MCP group and 1 eye (2.50%) in secondary MCP had PPOI exposure, which occurred before fitting the prostheses. After prosthesis was fit successfully, the excessive discharge and granuloma were 33.9% and 1.79% in PPOI group-only, 53.3% and 8.9% in primary MCP group, and 52.5% and 7.5% in secondary MCP group, respectively. CONCLUSION: Both primary and secondary placements of MCP into the PPOI following enucleation can help patients to obtain desirable prosthetic motility, but may be associated with more complications. The primary placement of MCP with skilled operation in selected patients is more recommendable than secondary placement.

Conjugated polyelectrolytes with aggregation-enhanced emission characteristics: synthesis and their biological applications.

Conjugated polyelectrolytes are promising candidates for the construction of fluorescent bioprobes. In this study, a series of water-soluble fluorescent polyelectrolytes have been designed and synthesized by means of the quaternization of their tetraphenylethene-containing polyyne precursors. The polyynes can be facilely prepared through Hay-Glaser polycoupling in high yields (up to 99%) with high molecular weights (up to 38,900). All the polymers exhibit a phenomenon of aggregation-induced or -enhanced emission. The fluorimetric titrations of biomolecules such as heparin, calf thymus DNA, RNA, bovine serum albumin, and human serum albumin to buffer solutions of the polyelectrolytes suggest that they are promising fluorescent bioprobes with high sensitivity and fast response. The emission intensity of the polyelectrolytes is enhanced by up to sevenfold upon binding with biomolecules through electrostatic and hydrophobic cooperative interactions. The polyelectrolytes can also serve as fluorescent visualizers for intracellular imaging with good biocompatibility and low autofluorescence interference.

Improved pharmacokinetics and reduced toxicity of brucine after encapsulation into stealth liposomes: role of phosphatidylcholine.

OBJECTIVE: Brucine was encapsulated into stealth liposomes using the ammonium sulfate gradient method to improve therapeutic index. MATERIALS AND METHODS: Four brucine stealth liposomal formulations were prepared, which were made from different phosphatidylcholines (PCs) with different phase transition temperatures (T(m)). The PCs used were soy phosphatidylcholine (SPC), dipalmitoyl phosphatidylcholine (DPPC), hydrogenated soy phosphatidylcholine (HSPC), and distearoyl phosphatidylcholine (DSPC). The stabilities, pharmacokinetics, and toxicities of these liposomal formulations were evaluated and compared. RESULTS: Size, zeta potential, and entrapment efficiency of brucine-loaded stealth liposomes (BSL) were not influenced by PC composition. In vitro release studies revealed that drug release rate increased with decreased T(m) of PCs, especially with the presence of rat plasma. After intravenous administration, the area under the curve (AUC) values of BSL-SPC, BSL-DPPC, BSL-HSPC, and BSL-DSPC in plasma were 7.71, 9.24, 53.83, and 56.83-fold as large as that of free brucine, respectively. The LD(50) values of brucine solution, BSL-SPC, BSL-DPPC, BSL-HSPC, and BSL-DSPC following intravenous injection were 13.17, 37.30, 37.69, 51.18, and 52.86 mg/kg, respectively. It was found in calcein retention experiments that the order of calcein retention in rat plasma was SPC < DPPC << HSPC < DSPC stealth liposomes. CONCLUSION: PC composition could exert significant influence on the stabilities, pharmacokinetics, and toxicities of brucine-loaded stealth liposomes. DSPC or HSPC with T(m) above 50°C should be used to prepare the stealth liposomal formulation for the intravenous delivery of brucine. However, it was found in the present paper that the pharmacokinetics and toxicity of BSL were not influenced by the PC composition when the T(m) of the PC was in the range of -20°C to 41°C.