Small Microparticles Research Articles

Indoor Airborne Microplastics: Human Health Importance and Effects of Air Filtration and Turbulence

Microplastics (MPs) are omnipresent particles that receive special attention because of their persistent nature and their potential impact on human disease and on the environment. Most MPs are generated by the degradation of larger plastic items such as clothing, car tires, and discarded plastic materials. In indoor environments, where human beings spend most of their time, aerial MP levels are higher, and the majority are fibers produced from textiles. Airborne MPs indoors are a greater potential danger to humans than MPs ingested in food and drink. Fragments small enough to remain substantially suspended in the air column, the small airborne microparticles that are measured as PM10 and PM2.5, become available for assimilation by human beings through respiration, potentially producing various health problems. Larger MPs act by ingestion and skin contact. MPs can carry microorganisms and micropollutants adsorbed to their surfaces, facilitating their uptake and survival within the human body. Indoor airborne MPs thus represent emerging pollutants of fast-growing concern that are especially important as potential invaders of the human respiratory system, reaching the alveoli of the lungs and finally entering the circulatory system and other tissues. Since this direct human exposure to MP contamination via indoor air is so important, we discuss in this article the ways in which MP concentration and dispersal in indoor air can be affected by air turbulence that is induced by anthropogenic objects such as air conditioners, filters, and purifiers. Much evidence is equivocal and further research is necessary.

Graph‐theoretical chirality measure and chirality–property relations for chemical structures with multiscale mirror asymmetries

AbstractChirality is an essential geometric property unifying small molecules, biological macromolecules, inorganic nanomaterials, biological microparticles, and many other chemical structures. Numerous chirality measures have attempted to quantify this geometric property of mirror asymmetry and to correlate these measures with physical and chemical properties. However, their utility has been widely limited because these correlations have been largely notional. Furthermore, chirality measures also require prohibitively demanding computations, especially for chiral structures comprised of thousands of atoms. Acknowledging the fundamental problems with quantification of mirror asymmetry, including the ambiguity of sign‐variable pseudoscalar chirality measures, we revisit this subject because of the significance of quantifying chirality for quantitative biomimetics and describing the chirality of nanoscale materials that display chirality continuum and scale‐dependent mirror asymmetry. We apply the concept of torsion within the framework of differential geometry to the graph theoretical representation of chiral molecules and nanostructures to address some of the fundamental problems and practical limitations of other chirality measures. Chiral gold clusters and other chiral structures are used as models to elaborate a graph‐theoretical chirality (GTC) measure, demonstrating its applicability to chiral materials with different degrees of chirality at different scales. For specific cases, we show that GTC provides an adequate description of both the sign and magnitude of mirror asymmetry. The direct correlations with macroscopic properties, such as chiroptical spectra, are enhanced by using the hybrid chirality measures combining parameters from discrete mathematics and physics. Taking molecular helices as an example, we established a direct relation between GTC and optical activity, indicating that this chirality measure can be applied to chiral metamaterials and complex chiral constructs.

Clinical significance of small extracellular vesicles in cholangiocarcinoma.

Cholangiocarcinoma is an aggressive and heterogeneous malignancy originating from the bile duct epithelium. It is associated with poor prognosis and high mortality. The global incidence of cholangiocarcinoma is rising, and there is an urgent need for effective early diagnosis and treatment strategies to reduce the burden of this devastating tumor. Small extracellular vesicles, including exosomes and microparticles, are nanoscale vesicles formed by membranes that are released both normally and pathologically from cells, mediating the intercellular transfer of substances and information. Recent studies have demonstrated the involvement of small extracellular vesicles in numerous biological processes, as well as the proliferation, invasion, and metastasis of tumor cells. The present review summarizes the tumorigenic roles of small extracellular vesicles in the cholangiocarcinoma microenvironment. Owing to their unique composition, accessibility, and stability in biological fluids, small extracellular vesicles have emerged as ideal biomarkers for use in liquid biopsies for diagnosing and outcome prediction of cholangiocarcinoma. Specific tissue tropism, theoretical biocompatibility, low clearance, and strong biological barrier penetration of small extracellular vesicles make them suitable drug carriers for cancer therapy. Furthermore, the potential value of small extracellular vesicle-based therapies for cholangiocarcinoma is also reviewed.

Biomaterial-mediated intracellular control of macrophages for cell therapy in pro-inflammatory and pro-fibrotic conditions

Macrophages are key modulators of all inflammatory diseases and essential for their resolution, making macrophage cell therapy a promising strategy for regenerative medicine. However, since macrophages change rapidly in response to microenvironmental cues, their phenotype must be controlled post-administration. We present a tunable biomaterial-based strategy to control macrophages intracellularly via small molecule-releasing microparticles. Poly(lactic-co-glycolic acid) microparticles encapsulating the anti-inflammatory and anti-fibrotic drug dexamethasone were administered to macrophages in vitro, with uptake rates controlled by different loading regimes. Microparticle dose and dexamethasone content directly affected macrophage phenotype and phagocytic capacity, independent of particle content per cell, leading to an overall pro-reparative, anti-inflammatory, anti-fibrotic phenotype with increased phagocytic and ECM degrading functionality. Intracellularly controlled macrophages partially maintained this phenotype in vivo in a murine pulmonary fibrosis model, with more prominent effects in a pro-fibrotic environment compared to pro-inflammatory. These results suggest that intracellular control using biomaterials has the potential to control macrophage phenotype post-administration, which is essential for successful macrophage cell therapy.

Aging microplastics enhances the adsorption of pharmaceuticals in freshwater

Plastic pollution is an increasing environmental concern. Pollutants such as microplastics (< 5 mm) and pharmaceuticals often co-exist in the aquatic environment. The current study aimed to elucidate the interaction of pharmaceuticals with microplastics and ascertain how the process of photo-oxidation of microplastics affected the adsorption of the pharmaceuticals. To this end, a mixture containing ibuprofen, carbamazepine, fluoxetine, venlafaxine and ofloxacin (16 μmol L−1 each) was placed in contact with one of six either virgin or aged microplastic types. The virgin microplastics were acquired commercially and artificially aged in the laboratory. Polypropylene, polyethylene, polyethylene terephthalate, polyamide, polystyrene, and polyvinyl chloride microparticles at two sizes described as small (D50 < 35 μm) and large (D50 95–157 μm) were evaluated. Results demonstrated that the study of virgin particles may underestimate the adsorption of micropollutants onto microplastics. For virgin particles, only small microparticles of polypropylene, polyethylene, polyvinyl chloride, and both sizes of polyamide adsorbed pharmaceuticals. Aging the microplastics increased significantly the adsorption of pharmaceuticals by microplastics. Fluoxetine adsorbed onto all aged microplastics, from 18 % (large polyethylene terephthalate) to 99 % (small polypropylene). The current investigation highlights the potential of microplastics to act as a vector for pharmaceuticals in freshwater, especially after aging.

A Low-Cost Laser-Prototyped Microfluidic Device for Separating Cells and Bacteria

Simple and rapid fabrication of microfluidic devices can enable widespread implementation of lab-on-chip devices in resource-limited environments. However, currently most of the microfluidic devices are fabricated in cleanroom facilities that are well-funded and not accessible to most of the researchers in developing countries. Herein, a simple, low-cost, and reliable method is shown to fabricate microfluidic devices for separating cells and bacteria-size microparticles. For this purpose, serpentine and spiral microfluidic channels are designed and fabricated using rapid laser prototyping. This single inlet microfluidic device is shown to successfully separate yeast cells and smaller microparticles with an efficiency of 85% which is very promising for many lab-on-chip applications including cell-based diagnostics and therapeutics.

Antimicrobial and Flame-Retardant Coatings Prepared from Nano- and Microparticles of Unmodified and Nitrogen-Modified Polyphenols.

The purpose of this study was to elucidate the structures and functional properties of tannin- and lignin-derived nano- and microparticles and the coatings prepared from them. Nanoparticles prepared from technical lignins and water-insoluble tannin obtained from softwood bark showed large differences in the suspension testing of antibacterial efficacy against methicillin-resistant Staphylococcus aureus (MRSA) bacteria. A common factor among the most effective lignin nanoparticles was a relatively low molar mass of the lignin, but that alone did not guarantee high efficacy. Tannin nanoparticles showed good antibacterial activity both in suspension testing and as coatings applied onto cellulose. The nanoparticles of nitrogen-modified tannin and the small microparticles of nitrogen-modified kraft lignin exhibited promising flame-retardant parameters when applied as coatings on cellulose. These results illustrate the potential of nano- and microsized particles of unmodified and chemically modified polyphenols to provide functional coatings to cellulosic substrates for environments and applications with high hygiene and fire safety requirements.

Microencapsulation of Piscirickettsia salmonis Antigens for Fish Oral Immunization: Optimization and Stability Studies.

The development of fish oral vaccines is of great interest to the aquaculture industry due to the possibility of rapid vaccination of a large number of animals at reduced cost. In a previous study, we evaluated the effect of alginate-encapsulated Piscirickettsia salmonis antigens (AEPSA) incorporated in feed, effectively enhancing the immune response in Atlantic salmon (Salmo salar). In this study, we seek to characterize AEPSA produced by ionic gelation using an aerodynamically assisted jetting (AAJ) system, to optimize microencapsulation efficiency (EE%), to assess microparticle stability against environmental (pH, salinity and temperature) and gastrointestinal conditions, and to evaluate microparticle incorporation in fish feed pellets through micro-CT-scanning. The AAJ system was effective in obtaining small microparticles (d &lt; 20 μm) with a high EE% (97.92%). Environmental conditions (pH, salinity and temperature) generated instability in the microparticles, triggering protein release. 62.42% of the protein content was delivered at the intestinal level after in vitro digestion. Finally, micro-CT-scanning images confirmed microparticle incorporation in fish feed pellets. In conclusion, the AAJ system is effective at encapsulating P. salmonis antigens in alginate with a high EE% and a size small enough to be incorporated in fish feed and produce an oral vaccine.

ACECLOFENAC SOLUBILITY ENHANCEMENT BY SONO-PRECIPITATION METHOD: FORMULATION OPTIMIZATION, CHARACTERIZATION AND IN-VITRO EVALUATION

Aceclofenac is a commonly used NSAID drug for treatment of pain and inflammation. Aceclofenac has poor water solubility, hence it corresponds to BCS class II drug. Poor solubility leads to poor oral bioavailability, so a challenge for drug delivery. The objective of the present research work is to improve solubility of aceclofenac by using a novel combination of anti-solvent and sono-precipitation technique. Sonoprecipitation has several advantages over conventional methods, like it is cost effective, produces small particle, process is clean, etc. To make this formulation, we dissolved aceclofenac in ethanol and applied 250W sonification for 5 sec followed by 5 sec of interval. This process was repeated for 12 mins and produced micro-sized Aceclofenac dispersion. Further, we characterized and evaluated Aceclofenac dispersion by X-ray powder diffraction (XRPD), Fourier transform infrared (FT-IR) spectroscopy, differential scanning calorimetric (DSC) and in vitro solubility and dissolution rate. The results shows that sonoprecipitation process led to the development of partially amorphous microparticles. The particle size range of 1-3 μm with mean diameter of 1.59 μm. The in-vitro studies indicated that the saturation solubility and dissolution rate of aceclofenac microcrystals were enhanced by 2.5 folds and 2-fold respectively, as compared to crude aceclofenac. In conclusion, the process of combining the antisolvent precipitation under sonication produced small, uniform, and stable aceclofenac microparticles with enhanced dissolution, solubility, and bioavaibility.

Enhanced self-cleaning performance of bio-inspired micropillar-arrayed surface by shear

Inspired by the sliding behavior of gecko feet during climbing, the contribution of the shear effect to the self-cleaning performance of a bio-inspired micropillar-arrayed surface is studied through a load-shear-pull contact process. It is found that self-cleaning efficiency can be enhanced significantly by shear. The efficiency also depends on microparticle size. For the case of relatively large and small microparticles, self-cleaning efficiency increases first and then almost keeps a constant with the increase of shear distance at different preloads. For medium microparticles, shear can effectively improve self-cleaning efficiency only when the preload is small. The mechanical mechanism under such enhancement is mainly due to the varying contact states between microparticles and micropillars with the shear distance. When the shear distance is large enough, the final self-cleaning efficiency is not sensitive to shear distance anymore because the contact state reaches dynamic equilibrium. Based on such a self-cleaning mechanism of large microparticles, a simple and effective manipulator that can efficiently transfer solid particles is further proposed.

Small tumour microparticle enhances drug delivery efficiency and therapeutic antitumour efficacy

BackgroundTargeted delivery of chemotherapeutic drugs to tumour cells is a major challenge for cancer chemotherapy. Recent studies show that tumour cell-derived microparticles can be used as vectors to package chemotherapeutic drugs, and selectively deliver drugs to tumour cells. Nevertheless, since the particle size range of microparticles is relatively wide, the sizes may exhibit different pharmacokinetic characteristics in the body, which will have a great impact on the application of drug-loaded microparticles. Here in this report, we compare the characteristics, distribution in vivo and antitumour efficacy of small microparticles (SMPs, ≤ 200 nm) and large microparticles (LMPs, > 200 nm) which loaded with methotrexate, in order to screen out more suitable carrier sizes.ResultsIn vivo and in vitro studies have proved that the drug-loaded vesicles of SMPs (mainly 100–200 nm) are more reasonable, and the drug content and maintenance in tumour tissues. The time is significantly higher than that of LMPs (mainly 400–500 nm). At the same time, we found that SMPs can be better taken up and processed by DC cells to promote the proliferation of specific T cells. SMPs show obvious advantages in both drug delivery and immune activation, which is verified by the comparison of the efficacy of SMPs and LMPs in the treatment of solid tumours in mice.ConclusionsThe present data demonstrate that the SMPs had a higher cumulative concentration in tumour tissue, and the tumour suppressive effect was also significantly better than that of LMPs. It provides important process parameters for the drug-loaded vesicle delivery system. Future works will aim to expand production scale and improve the separation and purification process of the microparticles. Although the research and application of drug-loaded vesicles derived from tumour cells is still in its infancy, it has broad prospects for tumour therapy.

Adsorption of cyanotoxins on polypropylene and polyethylene terephthalate: Microplastics as vector of eight microcystin analogues

Plastics are utilised globally but are of environmental concern due to their persistence. The global presence of microplastics (particles <5 mm in all dimensions) in freshwater environments is increasingly reported, as has the presence of cyanobacterial toxins, including the microcystins. We elucidated the potential role of microplastics as a vector for eight microcystin analogues. Two sizes of polypropylene (PP) and polyethylene terephthalate (PET) microparticles were evaluated. The median particle size distribution (D50) was 8–28 μm for small particles, and 81–124 μm for large particles. Additionally, microcystin-LR and -LF were evaluated individually using small PP and PET to elucidate the adsorption behaviour in the absence of competition. Microcystin hydrophobicity, polymer material, and particle size were key factors influencing adsorption to the plastic microparticles. The small size PP microparticles demonstrated a high affinity for the 8 microcystin analogues. The proportion of microcystin adsorbed onto the small particles of PP after 48 h contact was between 83 and 100%, depending on the analogue. Of all analogues investigated, only microcystin-LW and -LF adsorbed onto the larger sized PP and PET microparticles. Individually, greater amounts of MC-LF adsorbed onto the small PET (19%) compared to when it was present in the mixture of microcystins (11%). While MC-LR did not adsorb onto small PET microparticles in the mixture, 5% adsorption was observed when individually in contact with small PET microparticles. The results demonstrated that microplastics can adsorb eight different microcystin analogues and that more hydrophobic analogues are more likely to adsorb than less hydrophobic analogues.

Comparative study of natural disintegrants, selection criteria for superdisintegrants

Natural super disintegrants have been used for fast dissolving tablets because they are biodegradable, chemically inert, non-harmful, more affordable and widely available. The natural polymer improves the properties of the tablet as it is commonly used as diluents and binders. Super explosives are those substances that promote rapid decomposition in a lesser amount compared to explosives. Super disintegrants are the vehicles added to the tablet formulation to promote the breakdown of tablets and capsules into small microparticles in aqueous media, leading to an increase in surface area and promoting rapid drug release. Some research is going to develop safe and effective medication with super disintegrating agents that can be dissolved rapidly to treat the disease.

An overview of Natural Superdisintegrants

The oral route is the most convenient route of administration for various drugs. It is viewed as the most convenient, most secure, and economical route for patients. Fast disintegrating tablets are popular these days as they disintegrate in the mouth within a few seconds without the use of water. The burdens of regularly used medications in pediatric and geriatric patients have been overwhelmed by quick-dissolving tablets. Natural superdisintegrants have been used for fast-dissolving tablets because they are biodegradable, chemically inert, non-harmful, more affordable, and generally accessible. Natural polymer improves the properties of the tablet as it is commonly used as diluents and binders. Natural super disintegrants decrease the release time and give healthful results to the patients. Most polymers are obtained from nature, they are cost-effective, non-toxic, and non-irritants. Disintegration is the most important step for releasing the drug from the tablet matrix to decrease the disintegration time. In this, drug and polymers come in contact with water, it swells, hydrate, and react chemically to release the drug in the mouth and gastrointestinal tract. Superdisintegrants are those substances that encourage the quick breaking down with a lesser amount contrasted with disintegrants. The quick disintegrants tablets are set up by utilizing suitable polymers which rely on the Physico-chemical properties of drugs and excipients, for example, drug and polymer compatibility, hardness and thickness of tablet, nature of drug and excipients, PH of drug and release parameters of drug formulation. Superdisintegrants are the vehicles added to tablet formulation to advance the breaking of tablets and capsules into small microparticles in aqueous media resulting in to increase in the surface area and promote quick drug release. The disintegrants have a significant capacity to oppose the efficacy of tablet binders and compression forces to form the tablet. Commonly there are three methods to incorporate disintegrants into the tablet: A. Inner addition, B. External expansion, C. Internal, and external addition. Most of the regularly based tablets are those expected to be swallow, disintegrate and release medicaments in the gastrointestinal tract but over a while tablets are manufactured to deliver medicaments in the mouth and gastrointestinal tract within few seconds of swallowing. It has been demonstrated that characteristic polymers are more effective than synthetic polymers. Some research is going to develop safe and effective medication with super disintegrating agents that can be dissolved rapidly to treat the disease.

Increased anti-inflammatory activity and enhanced phytochemical concentrations in superfine powders obtained by controlled differential sieving process from four medicinal plants.

Anti-inflammatory effect of Rosa canina, Salix alba, Scrophularia nodosa and Hedera helix were studied in LPS-stimulated primary peripheral blood mononuclear cells (PBMCs) from mice (n=18) by comparing homogeneous powders of small microparticles (50-100 μm, 100-180 μm and 180-315 μm) obtained from plants via a controlled differential sieving process (CDSp) versus total plant materials obtained via hydroethanolic (HE) extraction. Further, phytochemical composition of the fine powders and HE extracts was determined by LC-PDA-ESI/MS analyses. Results showed that a one-hour pretreatment of PBMCs with fine powders, particularly those with superfine particle sizes (i.e. 50-100 μm and 100-180 μm), significantly inhibited TNFα, IL-1β, IL-6 and NO production in LPS-stimulated PBMCs, by at least ca. 20% more than HE extracts (all, p<0.05). For each of the plants studied, their superfine powdered fractions were more concentrated in phenolic contents than their HE extracts. Overall, our results further confirm CDSp, as an environmentally friendly method, for improving the concentration of bioactive compounds as well as their biological activities.

Influence of Nano- and Small Microplastics on Ciliated Protozoan Spirostomum ambiguum (Müller, 1786) Ehrenberg, 1835

This study evaluated the uptake of secondary nano- and small microparticles by the protozoan Spirostomum ambiguum, comparing edible (baker’s yeasts) and inedible (red latex) particles. Secondary nano- and microplastic particles were prepared from household materials made of four different polymers and served to the protozoans separately and as two-component mixtures in different proportions. The number and content of food vacuoles formed by the protozoan were analyzed using a digital microscope. The microscopic results showed that the protozoans ingested the secondary microplastic particles to a similar degree as the latex microspheres but to a lesser extent compared to the nutritional food—baker’s yeasts. At the microplastic concentrations of 1000 and 10,000 particles mL−1, no food vacuoles were observed inside the cells, which may be a finding of great ecological importance. In the protozoans served two-component mixtures, both microplastics and yeasts were found in the vacuoles formed by the organisms. The egestion of two-component vacuoles by the protozoans was slower than that of vacuoles containing a single component.

Self-Cleaning Performance of the Micropillar-Arrayed Surface and Its Micro-Scale Mechanical Mechanism

The exceptional adhesive ability of geckos remains almost uninfluenced by contaminated surfaces, showing that the adhesion system of geckos has self-cleaning properties. Although there have been several studies on the self-cleaning performance of geckos and gecko-inspired synthetic adhesives, the microscale mechanical mechanism of self-cleaning is still unclear. In the present study, a micropillar-arrayed surface is fabricated using a template molding method to investigate its self-cleaning performance in a load-pull contact process. The effects of preload, microparticle size on self-cleaning properties are studied. The self-cleaning efficiency of the micropillar-arrayed surface is found to increase with an increase in the microparticle size. For large and small microparticles, self-cleaning efficiency increases with an increase in the preload. For medium microparticles, self-cleaning efficiency first increases and then decreases as the preload increases. The mechanical mechanism underlying such self-cleaning performance is further elucidated; it is mainly attributed to the competition among the elastic energy stored in the micropillars induced by the bending deformation, the interfacial adhesion energy between the microparticles and the deformed micropillars, and the interfacial adhesion energy between the microparticles and substrate, as well as the varying contact states between the microparticles and the deformed micropillars. The preload can not only change the contact states between the microparticles and the micropillar-arrayed surface but also influence the bending elastic energy stored in the micropillars. The results obtained in the present study can help deeply understand the self-cleaning mechanism of micropillar-arrayed surfaces as well as provide a guideline for designing functional surfaces with high self-cleaning efficiency.

Tumor Microenvironment and Clonal Monocytes of Chronic Myelomonocytic Leukemia Induce a Procoagulant Climate within the Tumor Niche

Context:Chronic myelomonocytic leukemia (CMML) is a myeloid hematological malignancy close to myelodysplastic syndromes (MDS) (Itzykson, Leukemia 2013).The role of tumor microenvironment (TME) in the pathogenesis of MDS is increasingly highlighted, particularly the interactions between mesenchymal stem cells (MSCs) and hematopoietic tumor cells within the endosteal niche (Raaijmakers, Nature 2010). Studies about CMML TME focused on the vascular niche and demonstrated an increased angiogenesis and higher medullar vascular endothelial growth factor rates (Aguayo, Blood 2000; Bellamy, Blood 2001). MSCs have been less studied in the specific subset of CMML.Moreover, cancer is associated with a procoagulant state participating in tumor development and metastasis process (d'Asti, Meth Mol Biol 2016). Monocytes are important cells regarding coagulation as they shed procoagulant, tissue factor (TF)-bearing microparticles (del Conde, Blood 2005).We hypothesized that MSCs and clonal monocytes induce a procoagulant “climate” within the tumor endosteal niche in CMML patients, via the extracellular vesicles (EVs) they release. This procoagulant state could participate to tumor development.Methods:We isolated MSCs from CMML (n=3) and control (n=3) patients' marrow aspirations, monocytes from CMML (n=3) and reactional monocytosis (n=4) patients' blood. We also cultured HL60 cell line as a reference, as HL60-derived EVs are procoagulant (Gheldof, Thromb Res 2014).HL60 and MSCs were cultured with classical conditions and incubated in a medium free of serum EVs 72 hours before EVs collect. Monocytes were cultured for 40 hours in a serum-free medium to induce vesiculation and prevent contamination from serum EVs.EVs were extracted by sequential centrifugations of culture supernatant. The pellets obtained after 10 000 g and 100 000 g ultra-centrifugations corresponded to the « medium EVs » containing mostly microparticles and « small EVs » respectively, containing exosomes along with small microparticles (Tkach, Cell 2016).Concentration, mean size and size distribution of these EVs were analyzed by Nanoparticle Tracking Analysis (NS300, Malvern, UK). We tested always the same number of EVs for hemostasis tests.The exploration of coagulation was mainly performed with thrombin generation assay (TGA). Phospholipids were systematically added so that the phospholipid concentration would not limit the coagulation reaction.A fibrinolysis assay was performed on EVs deriving from MSCs and HL60 with a new technique currently developed: fibrinography. Relying on fibrin properties of light diffusion, it is a structural analysis of the nanostructure of the fibrin clot displaying the number of protofibrils per fibrin fiber during the coagulation and lysis reactions.Results:We showed that the vesiculation rate of MSCs (i.e. the number of EVs released by one cell) is significantly higher than the vesiculation rate of HL60 cells and monocytes (p = 0.02). The mean size of medium EVs (226 nm) was significantly higher than the mean size of small EVs (188 nm, p = 0.01).TGA data are shown in the figure 1. With poor-platelet normal plasma, we showed that CMML MSCs but not control MSCs have a higher procoagulant activity than HL60 cells and 0.5pM of TF (Fig. 1A). We also demonstrated that small EVs derived from CMML monocytes and MSCs, but not from control cells, display a procoagulant activity (Fig. 1B and 1C).TGA experiments were repeated with FVII-deficient plasma and did not display any thrombin generation when EVs were added. This implies that EVs procoagulant activity is mediated by TF present in the EVs.Fibrinography coagulation data confirmed the TGA results and displayed a higher sensitivity than TGA during the early phase of coagulation. Analysis of fibrinolysis data showed a longer clot lysis time in presence of CMML small or medium EVs (p = 0.02) compared to healthy controls, corresponding to a higher clot resistance to fibrinolysis (Fig. 2).Conclusion:Overall, our findings reveal a procoagulant “climate” within the endosteal tumor niche in CMML mediated by clonal monocytes but also TME. This may induce a net of fibrin in the tumor hematopoietic niche, which could participate in leukemia progression. [Display omitted] DisclosuresPark:Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; Hospira/Pfizer: Research Funding; Celgene: Research Funding.

Using embedded alginate microparticles to tune the properties of in situ forming poly(N-isopropylacrylamide)-graft-chondroitin sulfate bioadhesive hydrogels for replacement and repair of the nucleus pulposus of the intervertebral disc.

Low back pain is a major public health issue associated with degeneration of the intervertebral disc (IVD). The early stages of degeneration are characterized by the dehydration of the central, gelatinous portion of the IVD, the nucleus pulposus (NP). One possible treatment approach is to replace the NP in the early stages of IVD degeneration with a hydrogel that restores healthy biomechanics while supporting tissue regeneration. The present study evaluates a novel thermosensitive hydrogel based on poly(N‐isopropylacrylamide‐graft‐chondroitin sulfate) (PNIPAAM‐g‐CS) for NP replacement. The hypothesis was tested that the addition of freeze‐dried, calcium crosslinked alginate microparticles (MPs) to aqueous solutions of PNIPAAm‐g‐CS would enable tuning of the rheological properties of the injectable solution, as well as the bioadhesive and mechanical properties of the thermally precipitated composite gel. Further, we hypothesized that the composite would support encapsulated cell viability and differentiation. Structure‐material property relationships were evaluated by varying MP concentration and diameter. The addition of high concentrations (50 mg/mL) of small MPs (20 ± 6 μm) resulted in the greatest improvement in injectability, compressive mechanical properties, and bioadhesive strength of PNIPAAm‐g‐CS. This combination of PNIPAAM‐g‐CS and alginate MPs supported the survival, proliferation, and differentiation of adipose derived mesenchymal stem cells toward an NP‐like phenotype in the presence of soluble GDF‐6. When implanted ex vivo into the intradiscal cavity of degenerated porcine IVDs, the formulation restored the compressive and neutral zone stiffnesses to intact values and resisted expulsion under lateral bending. Overall, results indicate the potential of the hydrogel composite to serve as a scaffold for supporting NP regeneration. This work uniquely demonstrates that encapsulation of re‐hydrating polysaccharide‐based MPs may be an effective method for improving key functional properties of in situ forming hydrogels for orthopedic tissue engineering applications.

A review: An overview of Natural Superdisintegrants

The oral route is the most convenient route of administration for various drugs. It is viewed as the most convenient, most secure, and economical route for patients. Fast disintegrating tablets are popular these days as they disintegrate in the mouth within a few seconds without the use of water. The burdens of regularly used medications in pediatric and geriatric patients have been overwhelmed by quick-dissolving tablets. Natural superdisintegrants have been used for fast-dissolving tablets because they are biodegradable, chemically inert, non-harmful, more affordable, and generally accessible. Natural polymer improves the properties of the tablet as it is commonly used as diluents and binders. Natural super disintegrants decrease the release time and give healthful results to the patients. Most polymers are obtained from nature, they are cost-effective, non-toxic, and non-irritants. Disintegration is the most important step for releasing the drug from the tablet matrix to decrease the disintegration time. In this, drug and polymers come in contact with water, it swells, hydrate, and react chemically to release the drug in the mouth and gastrointestinal tract. Superdisintegrants are those substances that encourage the quick breaking down with a lesser amount contrasted with disintegrants. The quick disintegrants tablets are set up by utilizing suitable polymers which rely on the Physico-Chemical properties of drugs and excipients, for example, drug and polymer compatibility, hardness and thickness of tablet, nature of drug and excipients, PH of drug and release parameters of drug formulation. Superdisintegrants are the vehicles added to tablet formulation to advance the breaking of tablets and capsules into small microparticles in aqueous media resulting in to increase in the surface area and promote quick drug release. The disintegrants have a significant capacity to oppose the efficacy of tablet binders and compression forces to form the tablet. Commonly there are three methods to incorporate disintegrants into the tablet: A. Inner addition, B. External expansion, C. Internal, and external addition. Most of the regularly based tablets are those expected to be swallow, disintegrate and release medicaments in the gastrointestinal tract but over a while tablets are manufactured to deliver medicaments in the mouth and gastrointestinal tract within few seconds of swallowing. It has been demonstrated that characteristic polymers are more effective than synthetic polymers. Some research is going to develop safe and effective medication with super disintegrating agents that can be dissolved rapidly to treat the disease.