Porous nanofibrous dressing enables mesenchymal stem cell spheroid formation and delivery to promote diabetic wound healing

Delayed and nonhealing of diabetic wounds imposes substantial economic burdens and physical pain on patients.Mesenchymal stem cells(MSCs)promote diabetic wound healing.Particularly when MSCs aggregate into multicellular spheroids,their therapeutic effect is enhanced.However,traditional culture platforms are inadequate for the efficient preparation and delivery of MSC spheroids,resulting in inefficiencies and inconveniences in MSC spheroid therapy.In this study,a three-dimensional porous nanofibrous dressing(NFD)is prepared using a combination of electrospinning and homogeneous freeze-drying.Using thermal crosslinking,the NFD not only achieves satisfactory elasticity but also maintains notable cytocompatibility.Through the design of its structure and chemical composition,the NFD allows MSCs to spontaneously form MSC spheroids with controllable sizes,serving as MSC spheroid delivery systems for diabetic wound sites.Most importantly,MSC spheroids cultured on the NFD exhibit improved secretion of vascular endothelial growth factor,basic fibroblast growth factor,and hepatocyte growth factor,thereby accelerating diabetic wound healing.The NFD provides a competitive strategy for MSC spheroid formation and delivery to promote diabetic wound healing.

Spatiotemporal pharmacometabolomics based on ambient mass spectrometry imaging to evaluate the metabolism and hepatotoxicity of amiodarone in HepG2 spheroids

Three-dimensional(3D)cell spheroid models combined with mass spectrometry imaging(MSI)enables innovative investigation of in vivo-like biological processes under different physiological and pathological conditions.Herein,airflow-assisted desorption electrospray ionization-MSI(AFADESI-MSI)was coupled with 3D HepG2 spheroids to assess the metabolism and hepatotoxicity of amiodarone(AMI).High-coverage imaging of>1100 endogenous metabolites in hepatocyte spheroids was achieved using AFADESI-MSI.Following AMI treatment at different times,15 metabolites of AMI involved in Ndesethylation,hydroxylation,deiodination,and desaturation metabolic reactions were identified,and according to their spatiotemporal dynamics features,the metabolic pathways of AMI were proposed.Subsequently,the temporal and spatial changes in metabolic disturbance within spheroids caused by drug exposure were obtained via metabolomic analysis.The main dysregulated metabolic pathways included arachidonic acid and glycerophospholipid metabolism,providing considerable evidence for the mechanism of AMI hepatotoxicity.In addition,a biomarker group of eight fatty acids was selected that provided improved indication of cell viability and could characterize the hepatotoxicity of AMI.The combination of AFADESI-MSI and HepG2 spheroids can simultaneously obtain spatiotemporal information for drugs,drug metabolites,and endogenous metabolites after AMI treatment,providing an effective tool for in vitro drug hepatotoxicity evaluation.

Ca^(2+)-induced myelin pathology precedes axonal spheroid formation and is mediated in part by store-operated Ca^(2+)entry after spinal cord injury

The formation of axonal spheroid is a common feature following spinal cord injury.To further understand the source of Ca^(2+)that mediates axonal spheroid formation,we used our previously characterized ex vivo mouse spinal cord model that allows precise perturbation of extracellular Ca^(2+).We performed twophoton excitation imaging of spinal cords isolated from Thy1YFP+transgenic mice and applied the lipophilic dye,Nile red,to record dynamic changes in dorsal column axons and their myelin sheaths respectively.We selectively released Ca^(2+)from internal stores using the Ca^(2+)ionophore ionomycin in the presence or absence of external Ca^(2+).We reported that ionomycin dose-dependently induces pathological changes in myelin and pronounced axonal spheroid formation in the presence of normal 2 m M Ca^(2+)artificial cerebrospinal fluid.In contrast,removal of external Ca^(2+)significantly decreased ionomycin-induced myelin and axonal spheroid formation at 2 hours but not at 1 hour after treatment.Using mice that express a neuron-specific Ca^(2+)indicator in spinal cord axons,we confirmed that ionomycin induced significant increases in intra-axonal Ca^(2+),but not in the absence of external Ca^(2+).Periaxonal swelling and the resultant disruption in the axo-myelinic interface often precedes and is negatively correlated with axonal spheroid formation.Pretreatment with YM58483(500 n M),a well-established blocker of store-operated Ca^(2+)entry,significantly decreased myelin injury and axonal spheroid formation.Collectively,these data reveal that ionomycin-induced depletion of internal Ca^(2+)stores and subsequent external Ca^(2+)entry through store-operated Ca^(2+)entry contributes to pathological changes in myelin and axonal spheroid formation,providing new targets to protect central myelinated fibers.

Primary porcine hepatocytes with portal vein serum cultured on microcarriers or in spheroidal aggregates

AIM To develop a culture mode providingdurable biomaterials with high yields andactivities used in bioartificial liver.METHODS Hepatocytes were isolated from awhole pig liver by Seglen’s method of orthotopicperfusion with collagenase.In culture onmicrocarriers,primary porcine hepatocyteswere inoculated at a concentration of 5×10~7/mLinto the static culture systems containing 2 g/LCytodex-3,then supplemented with 100 mL/Lfetal calf serum(FCS)or 100 mL/L porcineportal vein serum(PPVS)respectively.Inspheroidal aggregate culture hepatocytes wereinoculated into 100 mL siliconized flasks at aconcentration of 5.0×10~6/mL.RESULTS In culture on microcarriershepatocytes tended to aggregate on Cytodex-3obviously after being inoculated.Typical multi-cellular aggregated spheroids could be found inthe two systems 24 h-48 h after hepatocyteswere cultured.The morphological charact-eristics and synthetic functions were maintainedfor 5 wk in FCS culture system and 8 wk in PPVSculture system.In spheroidal aggregate cultureabout 80%-90% isolated hepatocytes becameaggregated spheroids 24h after cultured insuspension and mean diameter of the spheroidswas 100μm.The relationship among thehepatocytes resembled that in the liver in vivo.Synthetic functions of albumin and urea of the spheroids were twice those of hepatocytescultured on monolayers.CONCLUSION As high-yields and high-activitymodes of culture on microcarriers or inspheroidal aggregate culture with portal veinserum are promising to provide biomaterials forbioartificial liver(BAL)efficiently.

Effect of Plasma Spheroidization Process on the Microstructure and Crystallographic Phases of Silica, Alumina and Nickel Particles

During the plasma spheroidization process powders undergo different changes in their microstructures and crystal phases. In this paper, simple calculation of heat transfer between the plasma and a suspended particle was performed based on three hypotheses for the purpose of guiding experiments. Experimental investigation of the crystal phases and microstructural changes during the plasma processing was made using silica, alumina and nickel powders as starting materials. It has been revealed from the experimental results that these materials undergo different changes in crystal phases and microstructures, and these changes are essentially determined by the structures, properties and aggregate states of the starting materials.

New Spheroidizing Technique of Ultra-High Carbon Steel With Aluminum Addition

A new spheroidizing process of ultra-high carbon steel （UHCS） containing C 1.55%, Cr 1.45%, and Al 1.5% in mass percent has been proposed. The effect of processing parameters on the microstructure was analyzed. The UHCS produced by this new process has a microstructure with recrystallized ferrite matrix and fine and uniform carbide particles. After this spheroidizing, the UHCS exhibits good mechanical properties at ambient temperature, for example σb= 1 100 MPa, σs =915 MPa, δ=8% and high ratio of σs/σb.

Spheroidization and Ostwald Growth of Carbide in Isothermal Process of Hot-Deformed High Carbon Chromium Cast Steel

In isothermal spheroidizing process,the spheroidization and growth of the carbide formed in hot-deformed high-carbon chromium cast steel at high temperature were investigated.The results showed that the spheroidizing growth of carbide proceeds in such a way that the bigger carbide particles swallow the smaller ones,and the short rhabdoid carbides dissolve and are spheroidized by itself.When the samples were held at 720℃ for more than 3 h,the spheroidization is not obvious.The feature of the process is the size increment and the amount decrement of carbide particles.The empirical equation for growth rate of carbides was obtained.The volume fraction of carbides keeps constant.The growth process agrees well with Ostwald Ripening Law.

Numerical Simulation of Shrinkage Cavity Formation in Spheroidal Graphite Iron Castings Based on Micro Modeling

A micro-modeling method (MM) for the quantitative prediction of the shrinkage cavity formation in SGiron castings is proposed. The mathematical models describing the volume changes during the solidification ofspheroidal graphite cast iron are established based on the models of solidification kinetics. The shrinkage cavityformation of T-shaped SG iron castings is calculated with MM method. The calculated results are compared with theexperimental results. It is shown that the predicted size, shape and distribution of shrinkage cavity by MM methodare in good agreement with the measured results.

Study on the RF inductively coupled plasma spheroidization of refractory W and W-Ta alloy powders

Spherical powders with good flowability and high stacking density are mandatory for powder bed additive manufacturing. Nevertheless, the preparation of spherical refractory tungsten and tungsten alloy powders is a formidable task. In this paper, spherical refractory metal powders processed by high-energy stir ball milling and RF inductively coupled plasma were investigated. By utilizing the technical route, pure spherical tungsten powders were prepared successfully, the flowability increased from 10.7 s/50 g to 5.5 s/50 g and apparent density increased from 6.916 g cm-3 to 11.041 g cm-3. Alloying element tantalum can reduce the tendency to micro- crack during tungsten laser melting and rapid solidification process. Spherical W-6Ta （%wt） powders were prepared in this way, homogeneous dispersion of tantalum in a tungsten matrix occurred but a small amount of flake-like shape particles appeared after high-energy stir ball milling. The flake-like shape particles can hardly be spheroidized in subsequent RF inductively coupled plasma process, might result from the unique suspended state of flaky particles under complex electric and magnetic fields as well as plasma-particle heat exchange was different under various turbulence models. As a result, the flake-like shape particles cannot pass through the high-temperature area of thermal plasma torch and cannot be spheroidized properly.

DETERMINATION OF EFFECTIVE MODULI FOR FOAM PLASTICS BASED ON THREE PHASE SPHEROIDAL MODEL

The relations of bulk modulus, shear modulus, Young's modulus and the Poisson's ratio with porosity of foam plastics are determined by a three phase spheroidal model commonly used in Composite Mechanics. The results are compared with those using differential scheme. It is shown that the material properties derived from the present model normally are larger than those obtained by differential scheme for foam plastics with identical porosity. The differences in shear moduli and Young's moduli obtained by the two methods are small but they are larger for bulk moduli of incompressible matrix and Poisson's ratios. The Young's moduli of high density foam plastics derived by the present model agree better with experimental ones.

Formation mechanism of spheroidal carbide in ultra-low carbon ductile cast iron

The formation mechanism of the spheroidal carbide in the ultra-low carbon ductile cast iron fabricated by the metal mold casting technique was systematically investigated. The results demonstrated that the spheroidal carbide belonged to eutectic carbide and crystallized in the isolated eutectic liquid phase area. The formation process of the spheroidal carbide was related to the contact and the intersection between the primary dendrite and the secondary dendrite of austenite. The oxides of magnesium, rare earths and other elements can act as heterogeneous nucleation sites for the spheroidal carbide. It was also found that the amount of the spheroidal carbide would increase with an increase in carbon content. The cooling rate has an important influence on the spheroidal carbide under the same chemical composition condition.

Solving ground eigenvalue and eigenfunction of spheroidal wave equation at low frequency by supersymmetric quantum mechanics method

The spheroidal wave functions are found to have extensive applications in many branches of physics and mathematics. We use the perturbation method in supersymmetric quantum mechanics to obtain the analytic ground eigenvalue and the ground eigenfunction of the angular spheroidal wave equation at low frequency in a series form. Using this approach, the numerical determinations of the ground eigenvalue and the ground eigenfunction for small complex frequencies are also obtained.

USING HIGH Mg-CONTENT CORED-WIRE TO SPHEROIDIZE AND DESULPHURIZE DUCTILE IRON MELT IN INDUSTRIAL EXPERIMENTS

Mg-content cored-wire was used to desulphurize and spheroidize ductile iron melt in industrial experiments. The optimal feeding speed and suitable treatment temperature were determined in the experiments. And cored-wire method and pouring method were compared. Conclusions have been drawn that, under these conditions in the experiments, the optimal feeding speed is 15m/min, treatment temperature should be as low as possible, 1400-1450℃ generally; and cored-wire method can act more effective in ductile iron melt desulphurization and spheroid than pouring method.

Spheroidization of molybdenum powder by radio frequency thermal plasma

To control the morphology and particle size of dense spherical molybdenum powder prepared by radio frequency（RF） plasma from irregular molybdenum powder as a precursor, plasma process parameters were optimized in this paper. The effects of the carrier gas flow rate and molybdenum powder feeding rate on the shape and size of the final products were studied. The molybdenum powder morphology was examined using high-resolution scanning electron microscopy. The powder phases were analyzed by X-ray diffraction. The tap density and apparent density of the molybdenum powder were investigated using a Hall flow meter and a Scott volumeter. The optimal process parameters for the spherical molybdenum powder preparation are 50 g/min powder feeding rate and 0.6 m^3/h carrier gas rate. In addition, pure spherical molybdenum powder can be obtained from irregular powder, and the tap density is enhanced after plasma processing. The average size is reduced from 72 to 62 μm, and the tap density is increased from 2.7 to 6.2 g/cm^3. Therefore, RF plasma is a promising method for the preparation of high-density and high-purity spherical powders.

Spheroidization process in large-deformed high-carbon steel

In this study,the spheroidization process of large-deformed steel under various conditions was researched.Steel with a high carbon content （1.0％ C） was first treated thermomechanically using multipass rolling.Then it underwent spheroidization treatments at different heating temperatures,using various heating times and cooling rates.Spheroidization processes with a lower heating temperature,shorter heating time,or faster cooling rate than those of the traditional process all showed good results,indicating that the spheroidization process was promoted significantly by the large deformation process.Grain refinement and fragmentation of cementite,along with the large deformation process,promoted this spheroidization process.

Some paradoxical observations about spheroidal graphite degeneracy

Differential thermal analysis experiments have been performed on samples machined from Y2-blocks cast with different high-silicon spheroidal graphite irons. Depending on magnesium, silicon, cerium and antimony content, the as-cast microstructure showed various levels of chunky graphite in the central part of the blocks. In contrast, the microstructure of the materials after remelting and resolidification during differential thermal analysis consisted of lamellar or compacted graphite. The formation of chunky graphite in the as-cast microstructure is rationalized using an index or silicon equivalent that has been recently suggested. The differences in the microstructures after differential thermal analysis are discussed in terms of available free magnesium. Emphasis is finally put on the striking differences in characteristic size of the microstructures made of compacted graphite as compared to lamellar graphite and chunky graphite. This leads to tentative conclusions about growth of compacted and chunky graphite which would be worthy of further experimental investigations.

RESEARCH OF THE FEEDING SPEED ADOPTING CORED-WIRE METHOD TO SPHEROIDIZE DUCTILE IRON MELT

For settling the question of feeding speed in applying the cored-wire method to spheroidize ductile iron melt, ANSYS software was applied to simulate the heat transfer and mass transfer, and the melt time of the steel strip in the iron melt was determined by linking the heat transfer and mass transfer, and then the feeding speed was calcufated. Conclusions have been drawn that the iron layer was formed on the surface of the cored-wire during the wire-feeding process. The thickness is 0.073 mm when the temperature of the iron melt is 1500℃, the time from formation to remelting of the iron layer is 0.063 s. When the temperature of the iron melt is below 1500℃, the time taken for the steel strip to melt is rapidly shortened. When the temperature of the iron melt is above 1500℃, the variation amplitude of the steel strip melt change with time is gradually diminished. The melt time of the steel strip is rapidly increased with the increase of the steel strip thickness. When the temperature of the iron melt is 1500℃ and the carbon content is 4%, the melt time of a steel strip, which has a thickness of 0.5 mm, is thrice that of a steel strip whose thickness is 0.3 mm. The calculation results of the feeding speed are basically in agreement with the applied feeding speed in the factory.

Influence of boron on ferrite formation in copper-added spheroidal graphite cast iron

This paper reviews the original work of the authors published recently,describing the influence of B on the matrix of the Cuadded spheroidal graphite cast iron.The effect of Cu has been corrected as a ferrite formation promoter in the matrix of the grey cast iron by the usage of high-purity material.Also,this paper focuses on the ferrite formation and the observation of the Cu distribution in the B-added and B-free Cu-containing spheroidal graphite cast iron.The Cu film on the spheroidal graphite can be successfully observed in the B-free sample using a special etching method.However,in the B-added sample,no Cu film could be found,while the secondary graphite was formed on the surface of the spheroidal graphite.The interaction between B and Cu is stressed as a peculiar phenomenon by the employment of a contrast experiment of B and Mn.The heat treatment could make Cu precipitate more significantly in the eutectic cells and in the matrix in the form of large Cu particles because of the limited solubility of Cu.

Effect of the feeding rate on microstructure and properties of plasma spheroidized GH4169 powder

The growing interest in additive manufacturing of GH4169 alloy was accompanied by the demand on spherical GH4169 powders with high performance.The powder particles were treated by radio frequency plasma with the different feeding rates.The microstructure and morphology,the particle size distribution of as-treated powders were studied by scanning electron microscopy and laser particle size analysis.It was demonstrated that GH4169 powders with extremely fine followability were obtained by radio frequency plasma spheroidization technology.With the same plasma parameters,the spheroidization efficiency of the particles varied with the feeding rates.When the rate of the powder feeding rates was too small,the excessive absorption of the heating by the powders caused vaporization,then the collection decreased.When the feeding rates was too large,the powder particles were insufficiently absorbed,resulting in defects in the powders.The microstructure of the as-treated spherical particles was mainly cell crystals,columnar crystals,and even microcrystals.Under the suitable plasma parameters,the resulting powders haved a slightly increased average particle size,excellent spheroidization,surface smoothness,followability,and bulk ratio.