Novel preparation of controlled porosity particle/fibre loaded scaffolds using a hybrid micro-fluidic and electrohydrodynamic technique.

The purpose of this research was to produce multi-dimensional scaffolds containing biocompatible particles and fibres. To achieve this, two techniques were combined and used: T-Junction microfluidics and electrohydrodynamic (EHD) processing. The former was used to form layers of monodispersed bovine serum albumin (BSA) bubbles, which upon drying formed porous scaffolds. By altering the T-Junction processing parameters, bubbles with different diameters were produced and hence the scaffold porosity could be controlled. EHD processing was used to spray or spin poly(lactic-co-glycolic) (PLGA), polymethysilsesquioxane (PMSQ) and collagen particles/fibres onto the scaffolds during their production and after drying. As a result, multifunctional BSA scaffolds with controlled porosity containing PLGA, PMSQ and collagen particles/fibres were obtained. Product morphology was studied by optical and scanning electron microscopy. These products have potential applications in many advanced biomedical, pharmaceutical and cosmetic fields e.g. bone regeneration, drug delivery, cosmetic cream lathers, facial scrubbing creams etc

Preparation of monodisperse microbubbles using an integrated embedded capillary T-junction with electrohydrodynamic focusing.

This work investigates the generation of monodisperse microbubbles using a microfluidic setup combined with electrohydrodynamic processing. A basic T-junction microfluidic device was modified by applying an electrical potential difference across the outlet channel. A model glycerol air system was selected for the experiments. In order to investigate the influence of the electric field strength on bubble formation, the applied voltage was increased systematically up to 21 kV. The effect of solution viscosity and electrical conductivity was also investigated. It was found that with increasing electrical potential difference, the size of the microbubbles reduced to ~25% of the capillary diameter whilst their size distribution remained narrow (polydispersity index ~1%). A critical value of 12 kV was found above which no further significant reduction in the size of the microbubbles was observed. The findings suggest that the size of the bubbles formed in the T-junction (i.e. in the absence of the electric field) is strongly influenced by the viscosity of the solution. The eventual size of bubbles produced by the composite device, however, was only weakly dependent upon viscosity. Further experiments, in which the solution electrical conductivity was varied by the addition of a salt indicated that this had a much stronger influence upon bubble size

Alginate foam-based three-dimensional culture to investigate drug sensitivity in primary leukaemia cells

The development of assays for evaluating the sensitivity of leukaemia cells to anti-cancer agents is becoming an important aspect of personalized medicine. Conventional cell cultures lack the three-dimensional (3D) structure of the bone marrow (BM), the extracellular matrix and stromal components which are crucial for the growth and survival of leukaemia stem cells. To accurately predict the sensitivity of the leukaemia cells in an in vitro assay a culturing system containing the essential components of BM is required. In this study, we developed a porous calcium alginate foam-based scaffold to be used for 3D culture. The new 3D culture was shown to be cell compatible as it supported the proliferation of both normal haematopoietic and leukaemia cells. Our cell differential assay for myeloid markers showed that the porous foam-based 3D culture enhanced myeloid differentiation in both leukaemia and normal haematopoietic cells compared to two-dimensional culture. The foam-based scaffold reduced the sensitivity of the leukaemia cells to the tested antileukaemia agents in K562 and HL60 leukaemia cell line model and also primary myeloid leukaemia cells. This observation supports the application of calcium alginate foams as scaffold components of the 3D cultures for investigation of sensitivity to antileukaemia agents in primary myeloid cells

The comparision of glybenclamide and metformin-loaded bacterial cellulose/gelatin nanofibres produced by a portable electrohydrodynamic gun for diabetic wound healing

Wound dressings made from natural polymers are an important aspect of biomaterials. Protein-based materials are less likely to instigate an immunogenic response and have the capacity to degrade in vivo, also without triggering an inflammatory response. Therefore, gelatin (GEL) was chosen and combined with bacterial cellulose (BC) to produce nanofibres and the potential of an all-natural polymer construct was determined. GEL and BC were successfully electrospun with metformin (Met) and glybenclamide (Gb) using a portable, point of need electrospinning set up. The virgin fibre group exhibited a significant effect on the proliferation of L929 (mouse fibroblast) cells but all fibre samples can safely be applied on wound site without risk of cytotoxicity. According to the results obtained by animal tests, the GEL-BC-Gb group showed better recovery than the GEL-BC-Met group. Diabetic wounds treated with GEL-BC-Met were characterized by moderate re-epithelialization and partially organized granulation tissue. Moderate to complete re-epithelialization and well-formed granulation tissue were observed in diabetic wounds treated with GEL-BC-Gb. The histologic scores obtained on day 14 confirmed that the GEL-BC-Gb group played a stronger wound-healing role compared to the GEL-BC-Met group. The highest decrease of TNF-α level was observed in the GEL-BC-Gb group at the end of the experiment but there is no significant difference between drug-loaded fibre groups. Therefore, topical administration of Met and Gb in a sustained release form has a high potential for diabetic wound healing with high bioavailability and fewer systemic side effects but Gb showed better improvement according to the results of the animal tests

Drug Delivery Strategies for Platinum Based Chemotherapy

Few chemotherapeutics have had such an impact on cancer management as cis-diamminedichloridoplatinum(II) (CDDP), also known as cisplatin. The first member of the platinum based drug family, CDDP's potent toxicity in disrupting DNA replication has led to its widespread use in multi-drug therapies, with particular benefit in patients with testicular cancers. However, CDDP also produces significant side effects that limit the maximum systemic dose. Various strategies have been developed to address this challenge including encapsulation within micro- or nanocarriers and the use of external stimuli such as ultrasound to promote uptake and release. The aim of this article is to look at these strategies and recent scientific and clinical developments

Electrohydrodynamic encapsulation of cisplatin in poly (lactic-co-glycolic acid) nanoparticles for controlled drug delivery

Targeted delivery of potent, toxic chemotherapy drugs, such as cisplatin, is a significant area of research in cancer treatment. In this study, cisplatin was successfully encapsulated with high efficiency (>70%) in poly (lactic-co-glycolic acid) polymeric nanoparticles by using electrohydrodynamic atomization (EHDA) where applied voltage and solution flow rate as well as the concentration of cisplatin and polymer were varied to control the size of the particles. Thus, nanoparticles were produced with three different drug:polymer ratios (2.5, 5 and 10wt% cisplatin). It was shown that smaller nanoparticles were produced with 10wt% cisplatin. Furthermore, these demonstrated the best sustained release (smallest burst release). By fitting the experimental data with various kinetic models it was concluded that the release is dependent upon the particle morphology and the drug concentration. Thus, these particles have significant potential for cisplatin delivery with controlled dosage and release period that are crucial chemotherapy parameters

Differential interaction with TREM2 modulates microglial uptake of modified Aβ species.

Funder: Canadian Institutes of Health Research; Id: http://dx.doi.org/10.13039/501100000024Funder: Alzheimer's Association (Zenith Award)Funder: UK Alzheimer Society and ARUKFunder: Wellcome Trust Collaborative Award in ScienceRare coding variants of the microglial triggering receptor expressed on myeloid cells 2 (TREM2) confer an increased risk for Alzheimer's disease (AD) characterized by the progressive accumulation of aggregated forms of amyloid β peptides (Aβ). Aβ peptides are generated by proteolytic processing of the amyloid precursor protein (APP). Heterogeneity in proteolytic cleavages and additional post-translational modifications result in the production of several distinct Aβ variants that could differ in their aggregation behavior and toxic properties. Here, we sought to assess whether post-translational modifications of Aβ affect the interaction with TREM2. Biophysical and biochemical methods revealed that TREM2 preferentially interacts with oligomeric Aβ, and that phosphorylation of Aβ increases this interaction. Phosphorylation of Aβ also affected the TREM2 dependent interaction and phagocytosis by primary microglia and in APP transgenic mouse models. Thus, TREM2 function is important for sensing phosphorylated Aβ variants in distinct aggregation states and reduces the accumulation and deposition of these toxic Aβ species in preclinical models of Alzheimer's disease

TREM2 is required for microglial instruction of astrocytic synaptic engulfment in neurodevelopment

Variants in the microglial receptor TREM2 confer risk for multiple neurodegenerative diseases. However, it remains unknown how this receptor functions on microglia to modulate these diverse neuropathologies. To understand the role of TREM2 on microglia more generally, we investigated changes in microglial function in Trem2−/− mice. We found that loss of TREM2 impairs normal neurodevelopment, resulting in reduced synapse number across the cortex and hippocampus in 1-month-old mice. This reduction in synapse number was not due directly to alterations in interactions between microglia and synapses. Rather, TREM2 was required for microglia to limit synaptic engulfment by astrocytes during development. While these changes were largely normalized later in adulthood, high fat diet administration was sufficient to reinitiate TREM2-dependent modulation of synapse loss. Together, this identifies a novel role for microglia in instructing synaptic pruning by astrocytes to broadly regulate appropriate synaptic refinement, and suggests novel candidate mechanisms for how TREM2 and microglia could influence synaptic loss in brain injury and disease

Instance reduction for one-class classification

Instance reduction techniques are data preprocessing methods originally developed to enhance the nearest neighbor rule for standard classification. They reduce the training data by selecting or generating representative examples of a given problem. These algorithms have been designed and widely analyzed in multi-class problems providing very competitive results. However, this issue was rarely addressed in the context of one-class classification. In this specific domain a reduction of the training set may not only decrease the classification time and classifier’s complexity, but also allows us to handle internal noisy data and simplify the data description boundary. We propose two methods for achieving this goal. The first one is a flexible framework that adjusts any instance reduction method to one-class scenario by introduction of meaningful artificial outliers. The second one is a novel modification of evolutionary instance reduction technique that is based on differential evolution and uses consistency measure for model evaluation in filter or wrapper modes. It is a powerful native one-class solution that does not require an access to counterexamples. Both of the proposed algorithms can be applied to any type of one-class classifier. On the basis of extensive computational experiments, we show that the proposed methods are highly efficient techniques to reduce the complexity and improve the classification performance in one-class scenarios

Study on the effects of preheated wall/plates in microthruster systems

In the present paper, effects of pre-heated walls/plates on microthrusters performance are studied using a DSMC/NS solver. Three microthruster configuration types are studied. Type 1 is a cold gas microthrster. Microthruster type 2 has pre-heated walls. Pre-heated plates are inserted inside the chamber of microthruster type 3. It is observed that in microthruster type 2 the flow is accelerated and the specific impulse is elevated. However, by insertion of the pre-heated plates in microthruster type 3, viscous effects have stronger negative influence and the thrust is decreased. By implementing temperature gradients on walls in type 2 and on plates in type 3, it is observed that a higher temperature gradient enhances performance parameters of microthruters. Among all types of microthrusters, microthruster type 2 with pre-heated walls has the highest thrust and specific impulse. Microthruster type 3 with a temperature gradient of 300-500K has the minimum thrust due to a considerable decrease in the mass flow rate