Bactericidal strontium-releasing injectable bone cements based on bioactive glasses

Strontium-releasing injectable bone cements may have the potential to prevent implant-related infections through the bactericidal action of strontium, while enhancing bone formation in patients suffering from osteoporosis. A melt-derived bioactive glass (BG) series (SiO₂–CaO–CaF₂–MgO) with 0–50% of calcium substituted with strontium on a molar base were produced. By mixing glass powder, poly(acrylic acid) and water, cements were obtained which can be delivered by injection and set in situ, giving compressive strength of up to 35 MPa. Strontium release was dependent on BG composition with increasing strontium substitution resulting in higher concentrations in the medium. Bactericidal effects were tested on Staphylococcus aureus and Streptococcus faecalis; cell counts were reduced by up to three orders of magnitude over 6 days. Results show that bactericidal action can be increased through BG strontium substitution, allowing for the design of novel antimicrobial and bone enhancing cements for use in vertebroplasty or kyphoplasty for treating osteoporosis-related vertebral compression fractures.     

含锶硼酸盐基生物玻璃经晶化处理后对其溶解性能及体外生物活性的影响

通过对含锶硼酸盐基玻璃进行微晶化处理,以考察该玻璃由玻璃态转化为晶态时体外生物活性和降解性的改变。采用熔融法制备不同锶含量(n(SrO)=0、2%、6%)的硼硅酸盐生物玻璃,然后在700℃/4h条件下微晶化处理,分别获得微晶化前后的试样。将各组玻璃及微晶化的样品浸泡在类似于生理模拟液的0.02mol/L的K2HPO4溶液中(以1g玻璃对应100mL浸泡液的比例),置于37℃恒温条件下,进行体外生物矿化反应。用XRD和FT-IR对反应后产物进行表征,并测定不同浸泡时间下样品的质量损失率以及浸泡液的pH值。结果表明,微晶化处理前后的含锶的硼硅酸盐玻璃试样在浸泡实验中都可以转化成含锶羟基磷灰石,即微晶化后的试样仍然具有体外生物活性;并且微晶化后试样的离子溶出速度能够减缓,降低了原玻璃相对骨组织生长来说的较高的降解速度,可以更加匹配骨组织生长的周期。因此,微晶化处理硼硅酸盐玻璃可实现对降解速度的调控,使该微晶化的生物玻璃有可能在骨组织修复中得到临床应用。     

含锶硼硅酸盐生物玻璃的降解性能及体外生物活性

研究了含锶硼硅酸盐玻璃的体外生物活性和降解性。采用熔融法制备不同锶含量(SrO含量为0、2%、4%、6%、8%、10%、12%(摩尔分数))的硼硅酸盐生物玻璃粉末,粒径范围为150～300μm。将各组玻璃样品浸泡在0.02mol/L的K2HPO4溶液中,置于37℃恒温条件下,进行体外生物矿化反应。通过对反应样品的质量损失以及浸泡液pH值进行测定,并用XRD、FTIR以及SEM对反应过程和反应后产物进行表征。结果表明,含锶的硼硅酸盐玻璃在体外生物矿化反应中被生物降解,并转化为含锶羟基磷灰石,具有很好的生物活性和降解性;同时也观察到玻璃中引入锶元素后,在一定程度上控制玻璃的降解速度,进而控制硼的溶出速度,从一定程度上避免硼溶出速度过高可能带来的风险;ICP的结构也表明,当SrO为6%(摩尔分数),样品中硼元素溶出的速度最低。因此,用锶的含量可控制硼硅酸盐玻璃的降解速度,这种方法将在组织工程领域具有广阔的应用前景。     

可降解生物活性玻璃丝贯穿骨水泥的制备和性能研究

以硼硅酸盐玻璃丝作为增强材料,对具有较高孔隙率的骨水泥进行补强,利用SEM对骨水泥的显微结构进行了观察和分析,并对骨水泥的力学强度进行了测试。结果表明硼酸盐玻璃降解有助于环境中HAP的生成,30d后玻璃丝与骨水泥界面良好键合形成统一体,并且30d中骨水泥力学强度处于稳步增长态势。     

The effects of Sr concentration on physicochemical properties,bioactivity and biocompatibility of sub-micron bioactive glasses spheres

We synthetized a series of strontium-substituted submicron bioactive glasses spheres (Sr-SBG, SiO₂-P₂O₅-CaO-SrO) in which strontium was substituted for calcium on a mole percentage basis, then investigated the effect of strontium-substituted amount on morphologies, physicochemical properties, apatite-forming bioactivity of SBG and evaluated the proliferation, differentiation and mineralization of Sr-SBG with different strontium substitution amounts by co-cultured with human dental pulp cells (HDPCs). Results showed that Sr-SBG with different strontium substitution amounts were successfully fabricated and substituting different strontium amounts did not affect the morphology and particle size of SBG. All the Sr-SBG possessed good apatite-forming ability, but substituting a certain amount of strontium for calcium would weaken the apatite-forming ability of SBG. Additionally, all the Sr-SBG extractions promoted proliferation, early odontogenic differentiation and mineralization of HDPCs, however, the cell proliferation, differentiation and mineralization abilities would be reduced when the substituted amount of strontium was excess (15 mol%). This study suggests that Sr-SBG with moderate strontium substitution amounts can be used as a more promising biomaterial for dental repair.     

Influence of calcium and phosphorus release from bioactive glasses on viability and differentiation of dental pulp stem cells

The release of ions that can significantly contribute toward cellular response is an important characteristic of bioactive glasses (BG). Here, ionic extracts of three different compositions of BG powders in 60 mol% SiO₂, x mol% CaO (x = 28, 32 and 36), x mol% P₂O₅ (x = 12, 8 and 4) compositional system were utilized to study their effect on the viability, differentiation and mineralization of dental pulp stem cells (DPSCs) in vitro. ICP was applied to detect the exact ionic concentrations released from different composition of BG. DPSCs treated with conditioned media from the glass with 4 mol% P₂O₅ (BGCM1, media containing 44.01 ± 0.6 mg/L Si, 61.72 ± 0.1 mg/L Ca and 7.57 ± 0.01 mg/L P) were more metabolically active compared to conditioned media from the glass with 8 mol% P₂O₅ (BGCM2, media with 47.36 ± 0.7 mg/L Si, 57.4 ± 0.1 mg/L Ca and 14.54 ± 0.2 mg/L P), at all times tested, but in all cases the process was slower than the control. Cells exposed to media conditioned by the glass with 12 mol% P₂O₅ (BGCM3, 40.46 ± 0.5 mg/L Si, 61. 85 ± 0.3 mg/L Ca and 28.43 ± 0.3 mg/L P) responded differently, such that cells showed to be more metabolically active than control at day 3, but then similar to or lower than control at higher time points. Differentiation of DPSCs toward osteogenic lineage in the presence of BGCM was assessed by Alizarin red staining. Cells treated with high phosphate BGCM3 displayed a higher density of red mineralized nodules than cells treated with BGCM1 and BGCM2 after 21 days of culture in non-osteogenic medium. BGCM3 was therefore chosen for gene expression studies. Osteogenic differentiation of DPSCs in the presence and/or absence of BGCM3 or osteogenic supplements were studied by RT-PCR. Overall, the results demonstrated that, in the absence of osteogenic supplements, BGCM3 group showed a significantly higher mRNA expression levels for alkaline phosphatase at day 7, osteopontin and osteonectin at days 7 and 14, and a high level of collagen I at day 14, compared to negative control group (BM?). Overall, the results obtained from BGCM3 group are beneficial for the design and manufacture of scaffolds or particulates with tailored ion release for a range of bone repair applications.     

Preparation,characterization, in vitro bioactivity and protein loading/release property of mesoporous bioactive glass microspheres with different compositions

Mesoporous bioactive glass microspheres (MBGMs) with large mesopores have attracted considerable attention in the field of bone tissue regeneration and drug delivery systems due to their excellent bioactivity, biocompatibility and high specific area. In this study, a loose structure of MBGMs with adjustable chemical compositions was synthesized by the combination of sol-gel and water-in-oil (W/O) microemulsion. All the prepared MBGMs possessed a large mesopore diameter that increased with CaO content, a high surface area and good apatite-inducing formation ability. In vitro protein absorption and release assays demonstrated that the MBGMs exhibited decreased loading efficiency and burst release behavior as the CaO content increased. Additionally, an enhanced BSA-loading amount and prolonged release curve were obtained after the surfaces of MBGMs were modified by amine groups. Furthermore, the preliminary in vitro cell experiments showed that MBGMs exhibited good biocompatibility. The results indicated that MBGMs could be a promising candidate as a drug/protein carrier for bone tissue regeneration.     

Facile synthesis and in vitro bioactivity of radial mesoporous bioactive glass with high phosphorus and calcium content

A novel uniform monodispersed radial mesoporous bioactive glass nanosphere (MBG) with high phosphorus and calcium content has been successfully synthesized. The synthesis was first taken place in a cyclohexane-water biphasic stratification reaction system, which fabricated the radial mesoporous SiO₂-P₂O₅ nanosphere (SPN) using hexadecyltrimethyl ammonium bromide (CTAB) as a template agent and triethanolamine (TEA) as a hydrolysis catalyst. Solid reactions were then carried out to synthesize SiO₂-CaO-P₂O₅ MBG using SPN as both the silicon source and phosphorus source, and Ca(NO₃)₂ as the calcium source. The prepared MBG not only displayed the radial structure and high specific surface area (~321 m²/g), but also had high phosphorus and calcium content. The results of energy dispersive spectrometer (EDS) demonstrated that P₂O₅ content was enhanced by properly increasing the reaction temperature. The in vitro bioactivity test showed that MBG had an excellent ability of inducing apatite formation. Furthermore, the MBG showed excellent biocompatibility at a low concentration of 50–100 μg/mL in vitro, and it would have a promising prospect as drug delivery system for bone tissue regeneration.     

Fluorescence properties and energy transfer mechanism of Sm ion in lead telluroborate glasses

We report the fluorescence properties of Sm³⁺-doped lead telluroborate glasses of composition PbF₂.TeO₂.H₃BO₃.Sm₂O₃ as a function of Sm³⁺ concentration. A Judd-Ofelt scheme was used to determine the intensity parameters and radiative properties of Sm³⁺ ion. The emission and decay measurements were carried out at 402 nm excitation. Beyond 1.0 mol% Sm³⁺ concentration, the luminescence quenching is observed. The decay curves of ⁴G_5/2 level are well fitted to a single exponential function. The evaluated radiative properties suggest that the ⁴G_5/2 → ⁶H_7/2 transition is responsible for reddish-orange luminescence which might be used in the development of visible lasers.     

制备方法对高分子载药涂层结构和体外释放动力学的影响

分别采用浸涂法和喷涂法在316L不锈钢基体表面制备含雷帕霉素的丙烯酸树脂缓释涂层,并使用FTIR、SEM及DSC对涂层中雷帕霉素的物化状态进行了测试和分析,测试了上述两种方法制备的药物洗脱支架的体外药物释放动力学曲线,并分析了两种制备方法之间的差异.结果表明上述两种方法制备的含药涂层药物分布状态存在一定差异,药物释放速率有所不同,以浸涂法制备的含药涂层释放速率更快.     

Influence of surface modification on the apatite formation and corrosion behavior of Ti and Ti-15Mo alloy for biomedical applications

Commercially pure Ti and Ti-15Mo specimens were subjected to alkali-hydrogen peroxide and subsequent heat treatment to produce a nanoporous titanate gel layer with anatase phase. The surface morphology of the untreated, alkali-hydrogen peroxide treated and alkali-hydrogen peroxide heat treated specimens before and after 7 days of immersion in simulated body fluid was characterized using X-ray Diffractometer (XRD), Atomic Force Microscopy (AFM), Scanning Electron Microscopy (SEM) and Fourier Transform Infrared Spectroscopy (FT-IR). The formation of nanoporous titanate gel layer and the growth of apatite layer over the surface modified specimens after 7 days of immersion in simulated body fluid were confirmed. Further, the electrochemical corrosion behavior of all the specimens was examined using potentiodynamic polarization and electrochemical impedance spectroscopic techniques.     

添加Y对炮钢表面电弧离子镀(Ti,Al)N薄膜氧化性能的影响

利用电弧离子镀技术,在炮钢表面沉积TiAlN和TiAlYN两种薄膜,研究添加1%(原子分数)Y对(Ti,Al)N薄膜氧化性能的影响。两种沉积薄膜的样品在空气中850℃下氧化10h,用SEM、EDAX和XRD分别分析两种薄膜的形貌、成分及相组成。结果表明,在空气中850℃下氧化10h后,两种薄膜的氧化产物均为Al2O3和TiO2的混合氧化物;TiAlN薄膜的动力学曲线呈近似直线规律,而TiAlYN薄膜动力学曲线符合抛物线规律;前者表面氧化物晶粒粗大,而后者表面氧化物晶粒细小,且氧化膜厚度不足前者的一半;添加Y可以减少膜层表面液滴的数量,提高膜层的抗氧化性能。     

Influence of hydroxypropyl methylcellulose mixture,apparent viscosity,and tablet hardness on drug release using a 2(3) full factorial design

This study investigates the effects of three factors: (1) use of a mixture of two different grades of hydroxypropyl methylcellulose (HPMC), (2) apparent viscosity, and (3) tablet hardness on drug release profiles of extended-release matrix tablets. The lot-to-lot apparent viscosity difference of HPMC K15M on in vitro dissolution was also investigated. Four test formulations were made, each containing 10% of a very water-soluble active pharmaceutical ingredient (API), 32% HPMC K15M, or a mixture of HPMC K100LV and HPMC K100M, 56% diluents, and 2% lubricants. Each formulation was made at two hardness levels. A 2³ full factorial design was used to study various combinations of the three factors using eight experiments conducted in a randomized order. Dissolution studies were performed in USP apparatus I. The values of t_50% (time in which 50% drug is released) and t_lag (lag time, the time taken by the matrix tablet edges to get hydrated and achieve a state of quasi-equilibrium before erosion and the advance of solvent front through the matrix occur) were calculated from each dissolution profile. The similarity factor (f₂) was also calculated for each dissolution profile against the target dissolution profile. A simple Higuchi-type equation was used to analyze the drug release profiles. Statistical analysis using analysis of variance (ANOVA) and similarity factor (f₂) values calculated from the data indicated no significant difference among the t_50% values and dissolution profiles respectively for all formulations. Within the 3.3-6 kp hardness range investigated, dissolution rates were found to be independent of tablet hardness for all the formulations. Although significantly shorter lag times were observed for the tablets formulated with low- and high-viscosity HPMC mixtures in comparison to those containing a single grade of HPMC, this change had no significant impact on the overall dissolution profiles indicated by the similarity factor f₂ values. From this study it can be concluded that lot-to-lot variability in apparent viscosity of HPMC should not be a concern in achieving similar dissolution profiles. Also, results indicated that within the viscosity range studied (12,000-19,500 cps) an HPMC mixture of two viscosity grades can be substituted for another HPMC grade if the apparent viscosity is comparable. Also, the drug release is diffusion-controlled and depends mostly on the viscosity of the gel layer formed.     

Corrosion and ion release behavior of ultra-fine grained bulk pure copper fabricated by ECAP in Hanks solution as potential biomaterial for contraception

Ultra-fine grained (UFG) bulk pure copper has been successfully fabricated by equal-channel angular pressing (ECAP), with the grain size about 380 nm after 8 passes. The potentiodynamic polarization results of the ECAP copper specimens tested in Hanks solution revealed that the corrosion current of UFG copper is higher than that of the coarse grained copper. The cupric ion release behaviors of UFG copper immersed in Hanks solution for 30 days only displayed a burst release during the first 3 days (in comparison to the 1-2 months for the conventional Cu) from 115 μg/day to 12.5 μg/day, after which the ion release remained constant and slow. During the immersion experiments, Cu₂O was the only corrosion product found on the surface and it took 10 days or so to form a uniform Cu₂O layer. Uniform corrosive damage on the surface and few localized corrosion is observed. The above results indicate that UFG copper could have high potential as biomedical materials for contraception.     

Si nanocrystals formation in SiO2 by ion implantation: The effects of RTA and UV irradiation on photoluminescence

Si ion implantation was widely used to synthesize specimens of SiO₂ containing supersaturated Si and subsequent high temperature annealing induces the formation of embedded luminescent Si nanocrystals. In this work, the potentialities of excimer UV-light (172 nm, 7.2 eV) irradiation and rapid thermal annealing (RTA) to enhance the photoluminescence and to achieve low temperature formation of Si nanocrystals have been investigated. The Si ions were introduced at acceleration energy of 180 keV to fluence of 7.5 × 10¹⁶ ions/cm². The implanted samples were subsequently irradiated with an excimer-UV lamp. After the process, the samples were rapidly thermal annealed before furnace annealing (FA). Photoluminescence spectra were measured at various stages at the process. We found that the luminescence intensity is strongly enhanced with excimer-UV irradiation and RTA. Moreover, effective visible photoluminescence is found to be observed even after FA at 900 °C, only for specimens treated with excimer-UV lamp and RTA. Based on our experimental results, we discuss the effects of excimer-UV lamp irradiation and RTA process on Si nanocrystals related photoluminescence.     

Solventless dry powder coating for sustained drug release using mechanochemical treatment based on the tri-component system of acetaminophen,carnauba wax and glidant

Objective: Solventless dry powder coating methods have many advantages compared to solvent-based methods: they are more economical, simpler, safer, more environmentally friendly and easier to scale up. The purpose of this study was to investigate a highly effective dry powder coating method using the mechanofusion system, a mechanochemical treatment equipped with high compressive and shearing force.Materials and methods: Acetaminophen (AAP) and carnauba wax (CW) were selected as core particles of the model drug and coating material, respectively. Mixtures of AAP and CW with and without talc were processed using the mechanofusion system.Results: Sustained AAP release was observed by selecting appropriate processing conditions for the rotation speed and the slit size. The dissolution rate of AAP processed with CW substantially decreased with an increase in talc content up to 40% of the amount of CW loaded. Increasing the coating amount by two-step addition of CW led to more effective coating and extended drug release. Scanning electron micrographs indicated that CW adhered and showed satisfactory coverage of the surface of AAP particles.Conclusion: Effective CW coating onto the AAP surface was successfully achieved by strictly controlling the processing conditions and the composition of core particles, coating material and glidant. Our mechanochemical dry powder coating method using the mechanofusion system is a simple and promising means of solventless pharmaceutical coating.     

Ca2+对悬浮培养HEK293细胞的细胞团形成、细胞生长和代谢的影响

利用HEK293细胞在悬浮培养中具有聚集成团的体外培养特性,在250ml的Bellco的搅拌培养体系中,以细胞团粒径、细胞粒径、细胞数、细胞活力、葡萄糖比消耗速率 (qglc)、乳酸比生产速率 (qlac) 和乳酸对葡萄糖得率 (Ylac/glc) 为观察指标,考察了HEK293细胞在Ca2 浓度设置为0μmol/L、250μmol/L、500μmol/L、750μmol/L和1000μmol/L的搅拌培养体系中的细胞团形成、细胞生长和代谢.实验发现:培养基中的Ca2 浓度决定着HEK293细胞在悬浮培养中能否形成细胞团并影响着细胞团的粒径分布和细胞团内细胞相互连接的紧密程度;在250～1000μmol/L的Ca2 浓度范围内,HEK293细胞团的平均粒径与培养基中的Ca2 浓度成正比;Ca2 浓度对以细胞团的形式悬浮培养的HEK293细胞的生长和代谢无明显的影响.实验结果提示,Ca2 浓度是调节HEK293细胞团粒径分布、维持悬浮细胞团中HEK293细胞正常生长和代谢的有效控制参数.     

Influence of Ag thickness on electrical, optical and structural properties of nanocrystalline MoO3/Ag/ITO multilayer for optoelectronic applications

In this study, MoO₃/Ag/ITO/glass (MAI) nano-multilayer films were deposited by the thermal evaporation technique and then were annealed in air atmosphere at 200 °C for 1 h. The effects of Ag layer thickness on electrical, optical and structural properties of the MoO₃(45 nm)/Ag(5-20 nm)/ITO(45 nm)/glass nano-multilayer films were investigated. The sheet resistance decreased rapidly with increasing Ag thickness. Above a thickness of 10 nm, the sheet resistances became somewhat saturated to a value of 3(Ω/□). The highest transparency over the visible wavelength region of spectrum (85%) was obtained for 10 nm Ag layer thickness. Carrier mobility, carrier concentrations, transmittance and reflectance of the layers were measured. The allowed direct band-gap for an Ag thickness range 5-20 nm was estimated to be in the range 3.58-3.71 eV. The XRD pattern showed that the films were polycrystalline. X-ray diffraction has shown that Ag layer has a (111) predominant orientation when deposited. The figure of merit was calculated for MAI multilayer films. It has been found that the Ag layer thickness is a very important factor in controlling the electrical and optical properties of MAI multilayer films. The optimum thickness of the Ag layer for these films was determined. The results exhibit that the MAI transparent electrode is a good structure for use as the anode of optoelectronic devices.     

Influence of MO/MF2 modifiers (M = Ca,Sr, Ba) on spectroscopic properties of Eu3+ ions in germanate and borate glasses

Series of Eu³⁺-doped lead-free germanate and borate glasses were synthesized. The MO glass modifiers (M = Ca, Sr or Ba) were partially or totally substituted by MF₂ in chemical composition. In contrast to samples modified by CaO/CaF₂ or SrO/SrF₂, the germanate glass samples containing BaO and/or BaF₂ are fully amorphous, while the lead-free borate glasses are fully amorphous, independently from glass modifiers. Effect of glass modifiers on spectroscopic properties of Eu³⁺ were systematically investigated.For that reason, excitation and emission spectra of Eu³⁺ ions in examined systems were registered. Based on the emission spectra, ratio of integrated luminescence intensity of the ⁵D₀ → ⁷F₂ transition to that of the ⁵D₀ → ⁷F₁ transition (R factor) was calculated. Moreover, the luminescence decay curves were collected and the luminescence lifetimes of the ⁵D₀ excited state of Eu³⁺ ions were determined in function of MF₂ concentration.     

Effect of mixture composition on the formation of pinch points in condensers and evaporators for zeotropic refrigerant mixtures: Influence des compositions de mélanges zéotropiques sur la formation de points de pincement dans les condenseurs et les évaporateurs utilisant ces mélanges

In a recent study, it was shown by the authors that perfect glide matching of heat transfer fluid and the refrigerant is difficult in condensers and evaporators for many zeotropic mixtures and also that pinch points can occur in both the condensers and evaporators due to the non-linear variation of enthalpy during phase change. Also, a simple method was presented for predicting the occurrence of pinch points. In this paper, the influence of mixture composition on occurrence of pinch points is studied. From the thermodynamic analysis, it is shown that multi-component mixtures are preferable over many wide boiling binary mixtures for various applications from the point of view of pinch points and glide matching. The results are illustrated with a number of examples.