Modification of human cancellous bone using Thai silk fibroin and gelatin for enhanced osteoconductive potential

The modification of human cancellous bone (hBONE) with silk fibroin/gelatin (SF/G) using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC)/N-hydroxysuccini-mide (NHS) crosslinking was established. The SF/G solutions at a weight ratio of 50/50 and the solution concentrations of 1, 2, and 4 wt % were studied. SF/G sub-matrix was formed on the surface and inside pore structure of hBONE. All hBONE scaffolds modified with SF/G showed smaller pore sizes, less porosity, and slightly lower compressive modulus than unmodified hBONE. SF/G sub-matrix was gradually biodegraded in collagenase solution along 4 days. The hBONE scaffolds modified with SF/G, particularly at 2 and 4 wt % solution concentrations, promoted attachment, proliferation, and osteogenic differentiation of bone marrow-derived mesenchymal stem cells (MSC), comparing to the original hBONE. The highest cell number, ALP activity and calcium production were observed for MSC cultured on the hBONE scaffolds modified with 4 wt % SF/G. The mineralization was also remarkably induced in the cases of modified hBONE scaffolds as observed from the deposited calcium phosphate by EDS. The modification of hBONE with SF/G was, therefore, the promising method to enhance the osteoconductive potential of human bone graft for bone tissue engineering.     

Preparation and characterization of collagen microspheres for sustained release of VEGF

In this study, we prepared injectable collagen microspheres for the sustained delivery of recombinant human vascular endothelial growth factor (rhVEGF) for tissue engineering. Collagen solution was formed into microspheres under a water-in-oil emulsion condition, followed by crosslinking with water-soluble carbodiimide. Various sizes of collagen microspheres in the range of 1–30 μm diameters could be obtained by controlling the surfactant concentration and rotating speed of the emulsified mixture. Particle size proportionally decreased with increasing the rotating speed (1.8 μm per 100 rpm increase in the range of 300–1,200 rpm) and surfactant concentration (3.1 μm per 0.1% increase in the range of 0.1–0.5%). The collagen microspheres showed a slight positive charge of 8.86 and 3.15 mV in phosphate-buffered saline and culture medium, respectively. Release study showed the sustained release of rhVEGF for 4 weeks. Released rhVEGF was able to induce capillary formation of human umbilical vein endothelial cells, indicating the maintenance of rhVEGF bioactivity after release. In conclusion, the results suggest that the collagen microspheres have potential for sustained release of rhVEGF.     

Preparation and characterization of molecularly imprinted poly(hydroxyethyl methacrylate) microspheres for sustained release of gatifloxacin

Molecularly imprinted poly(hydroxyethyl methacrylate) microspheres (PHEMA MIPMs) were prepared via precipitation polymerization in this article, using gatifloxacin (GFLX), hydroxyethyl methacrylate (HEMA), and ethylene glycol dimethacrylate (EGDMA) as template molecule, functional monomer and cross-linker, respectively. The effects of reaction medium, initial total monomers, cross-linker and molecular imprinting on the polymerization were investigated systematically. The interaction between GFLX and HEMA in pre-solution was studied by UV–Visible spectrophotometer, both size and morphology of products were characterized by a scanning electron microscope. When the total initial monomer concentration was 1 vol%, EGDMA content was 70 mol%, a group of uniform PHEMA MIPMs were prepared at different GFLX/MAA molar ratios, with diameter range from 2.06 ± 0.07 to 2.82 ± 0.20 μm. The results of drug loading and in vitro release experiments demonstrated that PHEMA MIPMs could achieve a higher GFLX loading content and a more acceptable sustained release than non-imprinted ones.     

Controlled release of imatinib mesylate from PLGA microspheres inhibit craniopharyngioma mediated angiogenesis

Poly(lactic-co-glycolic acid) microspheres loaded with imatinib mesylate has been developed as a new therapeutic strategy to prevent craniopharyngioma recurrence. Microspheres composed of different lactic/glycolic acid ratios, molecular weights and drug compositions were synthesized and loaded with imatinib mesylate by modified double-emulsion/solvent evaporation technique and subsequently characterized by particle-size distribution, scanning electron microscopy, encapsulation efficiency and in vitro drug release. Inhibitory potential of imatinib containing microspheres on tumor neovascularization was investigated on craniopharyngioma tumor samples by rat cornea angiogenesis assay. Results showed that microspheres in different LA:GA ratios [LA:GA 50:50 (G50), 75:25 (G25), 85:15 (G15)] considerably reduced neovascularization induced by recurrent tumor samples in an in vivo angiogenesis assay (P < 0.01). Our data indicate that local delivery of imatinib mesylate to the post-surgical tumoral cavity using biodegradable microspheres may be a promising biologically selective approach to prevent the recurrence of craniopharyngiomas, via inhibition of neovascularization.     

Evaluation of microporous polycaprolactone matrices for controlled delivery of antiviral microbicides to the female genital tract

Acyclovir (ACV) as a model antiviral microbicide, was incorporated in controlled-release polycaprolactone (PCL) matrices designed for application as intra-vaginal ring inserts (IVRs). Microporous materials incorporating acyclovir up to a level of ~10 % w/w were produced by rapidly cooling suspensions of drug powder in PCL solution followed by solvent extraction from the hardened matrices. Around 21, 50 and 78 % of the drug content was gradually released from matrices over 30 days in simulated vaginal fluid at 37 °C, corresponding to drug loadings of 5.9, 7.0 and 9.6 % w/w. The release behaviour of matrices having the lowest drug loading followed a zero order model, whereas, the release kinetics of 7.0 and 9.6 % ACV-loaded PCL matrices could be described effectively by the Higuchi model, suggesting that Fickian diffusion is controlling drug release. Corresponding values of the diffusion co-efficient for ACV in the PCL matrices of 3.16 × 10^?9 and 1.07 × 10^?8 cm²/s were calculated. Plaque reduction assays provided an IC₅₀ value of 1.09 μg/mL for acyclovir against HSV-2 and confirmed the antiviral activity of released acyclovir against HSV-2 replication in primate kidney cells (Vero) at levels ~70 % that of non-formulated acyclovir at day 30. Estimated minimum in vivo acyclovir concentrations produced by a PCL IVR (19 μg/mL) exceeded by a factor of 20 the IC₅₀ value against HSV-2 and the reported ACV vaginal concentrations in women (0.5–1.0 μg/mL) following oral administration. These findings recommend further investigations of PCL matrices for vaginal delivery of antiviral agents in the treatment and prevention of sexually transmitted infections such as AIDS.     

Bioactivity of porous biphasic calcium phosphate enhanced by recombinant human bone morphogenetic protein 2/silk fibroin microsphere

To prepare a bioactive bone substitute, which integrates biphasic calcium phosphate (BCP) and rhBMP-2/silk fibroin (SF) microsphere, and to evaluate its characteristics. Hydroxyapatite and β-tricalcium phosphate were integrated with a ratio of 60–40 %. RhBMP-2/SF (0.5 μg/1 mg) microsphere was prepared, and its rhBMP-2-release kinetics was assed. After joining pore-forming agent (Sodium chloride, NaCl), porous BCP/rhBMP-2/SF were manufactured, and its characteristics and bioactivity in vitro were evaluated. Mean diameter of rhBMP-2/SF microsphere was 398.7 ± 99.86 nm, with a loading rate of 4.53 ± 0.08 %. RhBMP-2 was released in a dual-phase pattern, of which fast-release (nearly half of protein released) focused on the initial 3 days, and slow-release sustained more than 28 days. With the increase in concentration of NaCl, greater was porosity and pore size, but smaller mechanical strength of BCP/rhBMP-2/SF. Material with 150 % (w/v) NaCl had an optimal performance, with a porosity of 78.83 %, pore size of 293.25 ± 42.77μm and mechanical strength of 31.03 MPa. Proliferation of human placenta-derived mesenchymal stem cells (hPMSCs) on leaching extract medium was similar to the normal medium (P = 0.89), which was better than that on control group (P = 0.03). Activity of alkaline phosphatase on BCP/rhBMP-2/SF surface was higher than on pure BCP at each time point except at 1 day (P < 0.05). RhBMP-2 has a burst release on early times and a sustaining release on later times. BCP/rhBMP-2/SF with 150 % (w/v) pore-forming agent has excellent porosity, pore size and mechanical strength. The biomaterial induces proliferation and differentiation hPMSCs effectively.     

Preparation of alginate–CaCl2 microspheres as resveratrol carriers

Resveratrol-loaded calcium alginate microspheres for prolonged drug release were prepared by ionic gelation of alginate with calcium chloride (CaCl₂). Further, resveratrol-loaded calcium alginate microspheres were developed using two concentrations of alginate (0.5 and 1 % w/v) and CaCl₂ (0.5 and 1 M) and an encapsulator equipped with a 300-μm nozzle. The mean particle size of the microspheres was between 175.52 and 244.03 μm, and an encapsulation efficiency (EE) of over 95 % was observed. FTIR spectroscopy indicated a polyelectrolyte interaction between alginate and CaCl₂; alginate microsphere thermograms were analyzed by differential scanning calorimetry. X-ray diffraction shows the crystalline change of microspheres by cross linking. The release profiles and EE increased depending on the CaCl₂ concentration, and a slow initial burst release was observed on freeze-dried microspheres. These results indicate that resveratrol-loaded calcium alginate microspheres can be used as a potential resveratrol delivery system in the food industry.     

Fluxless bonding of silicon wafers to molybdenum substrates using electroplated tin-rich solder

A novel fluxless bonding process of silicon wafer on molybdenum substrate is successfully developed. Si-to-Mo bonding can be used for packaging power devices, especially when a device consists of an entire wafer. 300 Å Cr layer and 1,000 Å Au layer are first deposited on Si wafers and Mo substrates. The Cr/Au dual layer is used as underbump metallurgy and seed layer of electroplating. To reduce plastic shear strain on the solder in a bonded pair, thick Sn layer (70 μm) is electroplated over Mo substrates having Cr/Au structure, followed immediately by thin (0.1 μm) Ag layer. This Ag layer acts as the capping layer to prevent inner Sn from oxidation. The bonding process is performed in 50 millitorrs vacuum to inhibit oxidation. The bonding condition is 290 °C for 15 min without the use of any flux. The bonding layer thickness is controlled at 50 μm by small spacers placed between Si wafer and Mo substrate. Microstructure and composition of the joints are studied under scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDX). Scanning acoustic microscopy (SAM) is also used to verify the quality of joints over the entire sample. Without using any flux, high quality and uniform bonding layer is achieved. The composition of the joint is more than 97 at.% Sn. No intermetallic compound layers exist in the joint. This novel fluxless bonding process should be valuable in packaging large high power devices.     

Preparation and characterization of protein-loaded polyanhydride microspheres

Poly(1,3-bis-(p-carboxyphenoxy propane)-co-(sebacic anhydride) (P(CPP-SA)) have the anhydride bonds in copolymer backbone, which are available for degradation on the base of passive hydrolysis. This chemical structure made it degraded within a short time in linear degradation rate. For this property, polyanhydrides are one of the most suitable biodegradable polymers employed as drug carriers. This paper aimed at researching the erosion and degradation of P(CPP-SA) microspheres with CPP/SA monomer ratios of 20:80, 35:65 and 50:50. In vitro protein release from the microspheres was also investigated in this paper. Human serum albumin (HSA) was used as the model protein. In this research, the microspheres degradation and drug release rate from microspheres can be adjusted by altering the CPP/SA ratios of P(CPP-SA). The features of surface erosion were observed in SEM. The structural integrity of HSA extracted from microspheres was detected by gel permeation chromatography, compared with native HSA. The results showed HSA remained its molecule weight after encapsulated.     

Preparation, evaluation and bioavailability studies of indomethacin-bees wax microspheres

The present study envisages the preparation of microspheres containing indomethacin (IM) as model drug and bees wax as carrier, and to compare the in vitro release and pharmacokinetics of prepared IM formulation with commercially available oral formulation Microcid^®SR. The microsphere formulations were prepared by meltable emulsified dispersion and cooling induced solidification. Surface morphology of microspheres has been evaluated using scanning electron microscopy (SEM). The SEM images revealed the spherical shape of microspheres and more than 98.0% of the isolated microspheres were in the size range 115–855 μm. Differential scanning calorimetry (DSC) and Fourier transform infrared (FTIR) spectroscopy studies indicated that the drug after encapsulation with bees wax was stable and compatible. A single dose randomized complete cross over study of IM (75 mg) microspheres was carried out on 8 healthy Albino sheeps. Plasma IM concentrations and other pharmacokinetic parameters obtained were statistically analyzed. The T _max, C _max, AUC_O-24 and T _1/2 values of Microcid^®SR and optimized formulation were 3.0 h, 2038 ± 51.31 ng/ml, 9528 ± 129.65 ng/ml h^?1, and 2.59 ± 0.02 h^?1; and 3.2 h, 1940 ± 22.61 ng/ml, 8751 ± 41.32 ng/ml h^?1, and 2.68 ± 0.02 h^?1, respectively. Beeswax microspheres showed controlled release and it can be concluded that both the prepared formulation and Microcid^®SR are bioequivalent.     

Preparation,characterization, and in vivo evaluation of insulin-loaded PLA–PEG microspheres for controlled parenteral drug delivery

Aim: The aim of this study was to prepare insulin-loaded poly(lactic acid)–polyethylene glycol microspheres that could control insulin release at least for 1 week and evaluate their in vivo performance in a streptozotocin-induced diabetic rat model. Methods: The microspheres were prepared using a water-in-oil-in-water double emulsion solvent evaporation technique. Different formulation variables influencing the yield, particle size, entrapment efficiency, and in vitro release profiles were investigated. The pharmacokinetic study of optimized formulation was performed with single dose in comparison with multiple dose of Humulin® 30/70 as a reference product in streptozotocin-induced diabetic rats. Results: The optimized formulation of insulin microspheres was nonporous, smooth-surfaced, and spherical in structure under scanning electron microscope with a mean particle size of 3.07 ×μm and entrapment efficiency of 42.74% of the theoretical amount incorporated. The in vitro insulin release profiles was characterized by a bimodal behavior with an initial burst release because of the insulin adsorbed on the microsphere surface, followed by slower and continuous release corresponding to the insulin entrapped in polymer matrix. Conclusions: The optimized formulation and reference were comparable in the extent of absorption. Consequently, these microspheres can be proposed as new controlled parenteral delivery system.     

Multiparticulate Drug Delivery System for the Treatment of Diabetes Mellitus: In Vitro and In Vivo Evaluation

Biodegradable microspheres of poly(?)caprolactone were prepared by solvent evaporation method for controlled release of repaglinide. The prepared microspheres were spherical in shape having smooth surface. The average diameter was in the range of 24 to 31.04 µm. Drug entrapment efficiency of the prepared microspheres was in the range of 68.81% to 79.30%. Differential scanning calorimetry and x-ray diffraction analyses indicated the amorphous dispersion of drug in the microspheres. The drug release was continued up to 24 h depending upon the formulation variables; drug release was slow from the microspheres which were prepared with higher concentration of polymer and as the initial drug loading was increased, the drug release was also increased. A non-Fickian transport was the mechanism of drug release for all the microspheres. The in vivo anti-diabetic activity performed on steptozotocin induced rats indicated that the plain repaglinide has shown maximum percentage of reduction in blood glucose at the end of 3 h and then the percentage of reduction in blood glucose was decreased. While in case of rats treated with PCL5 microspheres, the percentage of reduction in glucose level was slow as compared to plain repaglinide within 3 h, but it was gradually increased to 74.86% at the end of 24 h.     

Three-dimensional profilometric assessment of Er:YAG laser irradiated unsintered zirconia

This study evaluated the effects of different Er:YAG laser pulse width protocols on surface roughness, loss of volume of the material, and the step height formed of pre-sintered yttrium-stabilized tetragonal zirconia polycrystalline (Y-TZP) by three-dimensional profilometric assessment. Blocks of pre-sintered Y-TZP were cut providing 63 standard 5-mm-thick samples which were divided by surface treatment, as follows (n = 9): G50 (100 mJ/10 Hz/1 W-50 μs); G100 (?100 μs); G300 (?300 μs); G600 (?600 μs); G1000 (?1000 μs); GTC (tribochemical silica coating); and GNC (untreated). After treated or not, samples were sintered according to the manufacturer’s recommendations. Roughness, volume loss and step height were analyzed by 3D profilometric assessment with confocal laser microscopy. ANOVA and Tukey’s test (p < 0.05) detected that irradiated groups showed increased roughness in the groups G50, G100, G300, and G600 when compared to GTC and GNC groups. The G1000 group showed a completely flat and unfavorable surface for retention. The groups G50, G100, and G300 showed great loss of volume and the step height formed, which can lead to a gap on the crowns. In G600 was observed satisfactory roughness with little loss of volume and the step height formed similar to GTC. Irrespective of laser protocol, any of the specimens showed the presence of cracks. It is suggested that the pulse width 600 μs (G600) is the most suitable pulse width protocol as an alternative surface treatment, promoting micro-retention, with little loss of volume of material, comparable to silica coating treatment.     

Encapsulation and characterization of controlled release flurbiprofen loaded microspheres using beeswax as an encapsulating agent

The aim of the present study was to extend the use of flurbiprofen in clinical settings by avoiding its harmful gastric effects. For this purpose, we designed the controlled release solid lipid flurbiprofen microspheres (SLFM) by emulsion congealing technique. Drug was entrapped into gastro resistant biodegradable beeswax microspheres which were prepared at different drug/beeswax ratios 1:1, 1:2 and 1:3 using gelatin and tween 20 as emulsifying agents. The effect of emulsifiers and the effect drug/beeswax ratios were studied on hydration rate, encapsulating efficiency, micromeritic properties, scanning electron microscopy (SEM), fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), X-ray diffraction (X-RD) analysis and in vitro drug release at pH 1.2 for 2 h and at pH 6.8 for 10 h. SEM revealed that microspheres made with tween 20 were smooth while microspheres made with gelatin showed porous morphology, however, they were all spherical in nature. The practical yield (recovery) showed a dependence on drug-beeswax ratio and it was variable from 53 to 84%. High loading encapsulating efficiency of flurbiprofen from 8 to 94% was achieved. FTIR and DSC analysis confirmed the absence of any drug polymer interaction indicating drug stability during microencapsulation. X-RD of pure flurbiprofen shows sharp peaks, which decreases on encapsulation, indicating decrease in the crystallinity of drug in microspheres. The micromeritic studies confirmed the presence of excellent and good flow properties of microspheres. Entrapment efficiency, morphology, practical yield, hydration rate, flow properties demonstrated their dependence on the HLB value of emulsifiers and emulsifiers with higher HLB were found more appropriate for effective microencapsulation of flurbiprofen. The release kinetics followed zero order mechanism of drug release at pH 6.8. Release pattern depends on the morphology of flurbiprofen microspheres and amount of beeswax used in the microspheres preparation. The microspheres prepared with high HLB values i.e., tween 20 showed effective control of drug release from microspheres. The absence of drug release at pH 1.2 proved the suitability of beeswax for its use as a gastro resistant material.     

Preparation of methotrexate-loaded, large, highly-porous PLLA microspheres by a high-voltage electrostatic antisolvent process

A high-voltage (10 kV) electrostatic antisolvent process was used to prepare methotrexate (MTX)-loaded, large, highly-porous poly-l-lactide (PLLA) microspheres. MTX solution in dimethyl sulfoxide (DMSO) and PLLA solution in dichloromethane (DCM) were homogeneously mixed, and then ammonium bicarbonate (AB) aqueous solution was added. The mixed solution was emulsified by ultrasonication with Pluronic F127 (PF127) as an emulsion stabilizer. The emulsion was electrosprayed by the specific high-voltage apparatus and dropped into a 100 mL of ethanol, which acted as an antisolvent for the solute and extracted DMSO and DCM, causing the co-precipitation of PLLA and MTX, thus forming microspheres with AB aqueous micro-droplets uniformly inlaid. The obtained MTX–PLLA microspheres were subsequently lyophilized to obtain large, highly-porous MTX–PLLA microspheres, which exhibited an identifiable spherical shape and a rough surface furnished with open pores, with a mean particle size of 25.0 μm, mass median aerodynamic diameter of 3.1 ± 0.2 μm, fine-particle fraction of 57.1 ± 1.6 %, and porosity of 81.8 %; furthermore, they offered a sustained release of MTX. X-ray diffraction and Fourier transform-infrared spectra revealed that no crystallinity or alteration of chemical structure occurred during the high-voltage electrostatic antisolvent process, which in this study was proved to have great potential for preparing highly-porous drug-loaded polymer microspheres for use in pulmonary drug delivery.     

A silk fibroin/chitosan scaffold in combination with bone marrow-derived mesenchymal stem cells to repair cartilage defects in the rabbit knee

Bone marrow-derived mesenchymal stem cells (BMSCs) were seeded in a three-dimensional scaffold of silk fibroin (SF) and chitosan (CS) to repair cartilage defects in the rabbit knee. Totally 54 rabbits were randomly assigned to BMSCs + SF/CS scaffold, SF/CS scaffold and control groups. A cylindrical defect was created at the patellofemoral facet of the right knee of each rabbit and repaired by scaffold respectively. Samples were prepared at 4, 8 and 12 weeks post-surgery for gross observation, hematoxylin–eosin and toluidine blue staining, type II collagen immunohistochemistry, Wakitani histology. The results showed that differentiated BMSCs proliferated well in the scaffold. In the BMSCs + SF/CS scaffold group, the bone defect was nearly repaired, the scaffold was absorbed and immunohistochemistry was positive. In the SF/CS scaffold alone group, fiber-like tissues were observed, the scaffold was nearly degraded and immunohistochemistry was weakly positive. In the control group, the defect was not well repaired and positive immunoreactions were not detected. Modified Wakitani scores were superior in the BMSCs + SF/CS scaffold group compared with those in other groups at 4, 8 and 12 weeks (P < 0.05). A SF/CS scaffold can serve as carrier for stem cells to repair cartilage defects and may be used for cartilage tissue engineering.     

Carboxymethyldextran/magnetite hybrid microspheres designed for hyperthermia

Recently, organic–inorganic hybrids composed of derivatives of dextran, a polysaccharide, and magnetite nanoparticles have attracted much attention as novel thermoseeds. If they can be fabricated into microspheres of size 20–30 μm, they are expected to show not only hyperthermia effects but also embolization effects in human liver and kidney cancers. In this study, we examined the fabrication of carboxymethyldextran/magnetite microspheres using a water/oil emulsion as the reaction medium. Improvement of the chemical stability of the microcapsules by coating with silica using a sol–gel process was also investigated. The obtained hollow microspheres contained particles of size 20–30 μm. Silica coating using an appropriate catalyst for hydrolysis and polycondensation of alkoxysilanes was found to be effective for preventing dissolution and collapse in simulated body environments.     

Composite chitosan and calcium sulfate scaffold for dual delivery of vancomycin and recombinant human bone morphogenetic protein-2

A biodegradable, composite bone graft, composed of chitosan microspheres embedded in calcium sulfate, was evaluated in vitro for point-of-care loading and delivery of antibiotics and growth factors to prevent infection and stimulate healing in large bone injuries. Microspheres were loaded with rhBMP-2 or vancomycin prior to mixing into calcium sulfate loaded with vancomycin. Composites were evaluated for set time, drug release kinetics, and bacteriostatic/bactericidal activity of released vancomycin, induction of ALP expression by released rhBMP-2, and interaction of drugs on cells. Results showed the composite set in under 36 min and released vancomycin levels that were bactericidal to S. aureus (>MIC 8–16 μg/mL) for 18 days. Composites exhibited a 1 day-delayed release, followed by a continuous release of rhBMP-2 over 6 weeks; ranging from 0.06 to 1.49 ng/mL, and showed a dose dependent release based on initial loading. Released rhBMP-2 levels were, however, too low to induce detectable levels of ALP in W20-17 cells, due to the affinity of rhBMP-2 for calcium-based materials. With stimulating amounts of rhBMP-2 (>50 ng/mL), the ALP response from W-20-17 cells was inhibited when exposed to high vancomycin levels (1,800–3,600 μg/mL). This dual-delivery system is an attractive alternative to single delivery or preloaded systems for bone regeneration since it can simultaneously fight infection and deliver a potent growth factor. Additionally, this composite can accommodate a wide range of therapeutics and thus be customizable for specific patient needs, however, the potential interactive effects of multiple agents must be investigated to ensure that functional activity is not altered.     

Development of Micro-SQUID Magnetometers for Investigation of Quantum Tunneling of Magnetization in Nanometer-Size Magnetic Materials

We report development of micro superconducting quantum interference device (μ-SQUID) magnetometers for investigation of quantum tunneling of magnetization in μm- and nm-size magnetic materials. Both high- and low-temperature superconductor (HTS and LTS) based μ-SQUID magnetometers were fabricated and a three dimensional magnetic coil system was constructed for this purpose. The HTS-μ-SQUIDs with a hole of 4×9 μm² work at temperatures between 4.2 and 70 K and in magnetic fields up to 120 mT. A magnetization measurement of a ferrimagnetic micro-crystal was carried out at 35 K with an accuracy of 10^?9 emu. The development of LTS-μ-SQUIDs has been started in order to study much smaller magnetic materials in a mK temperature range. We present a preliminary result on the LTS-μ-SQUID with a hole of 1×1 μm². The critical current as a function of applied magnetic field shows the SQUID modulation at 4.2 K and up to 30 mT. The heat release associated with the present measurement method is estimated to be on the order of several microwatts.     

Strontium-substituted,luminescent and mesoporous hydroxyapatite microspheres for sustained drug release

The multifunctional strontium (Sr)-substituted hydroxyapatite microsphere was prepared via hydrothermal method, in which the luminescent and controlled drug release functions can be realized. The structure and morphology of the as-prepared microspheres were studied by using XRD, FTIR, SEM, TEM, HR-TEM, BET method. The optical properties was investigated by using photoluminescence (PL) and XPS measurement. Then, the as-prepared multifunctional microspheres were performed as a drug delivery carrier using vancomycin as a model drug. The experimental results show that the composition, morphology, luminescent properties and drug storage/release behaviour were obviously influenced by the amount of Sr. The microspheres with Sr²⁺/(Ca²⁺ + Sr²⁺) = 0.3 of Sr substitution showed the maximum specific surface area, best pore structure and strongest PL intensity. All the samples presented remarkable sustained drug release kinetics. In addition, the PL intensity of SrHA in the drug delivery system increased with the cumulative release time (amount) of vancomycin, which would make the drug release might be possibly tracked by the change of the luminescent intensity. Our study indicated a potential prospect that the fabricated multifunctional SrHA mesoporous microspheres might be applied in the field of bone regeneration and drug delivery.