Highly Porous and Drug-Loaded Amorphous Solid Dispersion Microfiber Scaffolds of Indomethacin Prepared by Melt Electrowriting

Melt electrowriting (MEW) is an additive manufacturing technology enabling the production of highly porous microfiber scaffolds, suggested in particular for use in biomedical applications, including drug delivery. Indomethacin (IND) is a nonselective anti-inflammatory drug, for which sublingual delivery could offer advantages such as rapid absorption by the veins in the mouth floor while overcoming the side effects of peroral delivery such as damage to the gastrointestinal mucosa barrier. This study introduces MEW as a processing method to obtain rapid-dissolving drug-releasing scaffolds, containing IND as a model drug, for sublingual drug delivery applications. For this, an amorphous solid dispersion (ASD) of IND in combination with a poly(2-oxazoline)-based amphiphilic triblock copolymer excipient is introduced, enabling ultra-high drug loading. We prepared highly porous, melt electrowritten drug-loaded scaffolds with different polymer/IND w/w ratios up to 1:2 and assessed their morphology, amorphicity, and IND release rate. The results show completely amorphous dispersion of the polymer and drug after MEW processing resulting in smooth and uniform fibers and rapid dissolution of the drug loaded scaffold. These first water-soluble melt electrowritten IND-loaded microfiber scaffolds break ground as a model for rapid sublingual delivery of ultra-high drug-loaded ASDs.Peer reviewe

Melt electrowriting of poly(vinylidene difluoride) using a heated collector

Previous research on the melt electrowriting (MEW) of poly(vinylidene difluoride) (PVDF) resulted in electroactive fibers, however, printing more than five layers is challenging. Here, we investigate the influence of a heated collector to adjust the solidification rate of the PVDF jet so that it adheres sufficiently to each layer. A collector temperature of 110 degrees C is required to improve fiber processing, resulting in a total of 20 fiber layers. For higher temperatures and higher layers, an interesting phenomenon occurred, where the intersection points of the fibers coalesced into periodic spheres of diameter 206 +/- 52 mu m (26G, 150 degrees C collector temperature, 2000 mm/min, 10 layers in x- and y-direction).The heated collector is an important component of a MEW printer that allows polymers with a high melting point to be processable with increased layers.Peer reviewe

Membership and behavior of ultra-low-diversity pathogen communities present in the gut of humans during prolonged critical illness.

UnlabelledWe analyzed the 16S rRNA amplicon composition in fecal samples of selected patients during their prolonged stay in an intensive care unit (ICU) and observed the emergence of ultra-low-diversity communities (1 to 4 bacterial taxa) in 30% of the patients. Bacteria associated with the genera Enterococcus and Staphylococcus and the family Enterobacteriaceae comprised the majority of these communities. The composition of cultured species from stool samples correlated to the 16S rRNA analysis and additionally revealed the emergence of Candida albicans and Candida glabrata in ~75% of cases. Four of 14 ICU patients harbored 2-member pathogen communities consisting of one Candida taxon and one bacterial taxon. Bacterial members displayed a high degree of resistance to multiple antibiotics. The virulence potential of the 2-member communities was examined in C. elegans during nutrient deprivation and exposure to opioids in order to mimic local conditions in the gut during critical illness. Under conditions of nutrient deprivation, the bacterial members attenuated the virulence of fungal members, leading to a "commensal lifestyle." However, exposure to opioids led to a breakdown in this commensalism in 2 of the ultra-low-diversity communities. Application of a novel antivirulence agent (phosphate-polyethylene glycol [Pi-PEG]) that creates local phosphate abundance prevented opioid-induced virulence among these pathogen communities, thus rescuing the commensal lifestyle. To conclude, the gut microflora in critically ill patients can consist of ultra-low-diversity communities of multidrug-resistant pathogenic microbes. Local environmental conditions in gut may direct pathogen communities to adapt to either a commensal style or a pathogenic style.ImportanceDuring critical illness, the normal gut microbiota becomes disrupted in response to host physiologic stress and antibiotic treatment. Here we demonstrate that the community structure of the gut microbiota during prolonged critical illness is dramatically changed such that in many cases only two-member pathogen communities remain. Most of these ultra-low-membership communities display low virulence when grouped together (i.e., a commensal lifestyle); individually, however, they can express highly harmful behaviors (i.e., a pathogenic lifestyle). The commensal lifestyle of the whole community can be shifted to a pathogenic one in response to host factors such as opioids that are released during physiologic stress and critical illness. This shift can be prevented by using compounds such as Pi-PEG15-20 that interrupt bacterial virulence expression. Taking the data together, this report characterizes the plasticity seen with respect to the choice between a commensal lifestyle and a pathogenic lifestyle among ultra-low-diversity pathogen communities that predominate in the gut during critical illness and offers novel strategies for prevention of sepsis

Ecological Conditions and Distribution of Gemor Tree Species in Central and East Kalimantan

The aim of this study was to determine the ecological conditions and distribution of gemor bark producing tree species at Tuanan village in Kapuas District, Central Kalimantan Province and Long Daliq village in Kutai Barat, East Kalimantan Province. In order to collect adequate vegetation data, several obser vation plots were laid out by using purposive sampling. Primary and secondary data were collected from the plot areas by obser ving directly the habitat and its ecological condition of vegetation. It was revealed that the gemor tree species tended to grow well on the habitats which have a thin layer of peat (< 2 m), pH 3 – 4 and in a humid climatic condition. Two gemor bark producing tree species were identidfied in the study areas, namely Nothaphoebe coriacea (Kosterm.) Kosterm. and N. umbelliflora Blume. The similarity level of vegetation composition at both sites (Kapuas and Kutai Barat Districts) was low. The tree species richness in the plot areas of Tuanan in Kapuas District, Central Kalimantan (82 species, 57 genera and 28 families) was higher than that found in Long Daliq, Kutai Barat District, East Kalimantan (38 species, 26 genera and 19 families)

Sex Impact on Knee and Ankle Muscle Extensor Forces During Loaded Running

Background: This study determined whether the knee and ankle muscle extensor forces increase when running with a body-borne load and whether these forces differ between the sexes. Methods: Thirty-six (twenty male and sixteen female) adults had the knee and ankle extensor force quantified when running 4.0 m/s with four body-borne loads (20, 25, 30, and 35 kg). Peak normalized (BW) and unnormalized (N) extensor muscle force, relative effort, and joint angle and angular velocity at peak muscle force for both the ankle and the knee were submitted to a mixed model ANOVA. Results: Significant load by sex interactions for knee unnormalized extensor force (p = 0.025) and relative effort (p = 0.040) were observed, as males exhibited greater knee muscle force and effort than females and increased their muscle force and effort with additional load. Males also exhibited greater ankle normalized and unnormalized extensor force (p = 0.004, p \u3c 0.001) and knee unnormalized force than females (p = 0.005). The load increased the normalized ankle and knee muscle force (p \u3c 0.001, p = 0.030) and relative effort (p \u3c 0.001, p = 0.044) and the unnormalized knee muscle force (p = 0.009). Conclusion: Running with a load requires greater knee and ankle extensor force, but males exhibited greater increases in muscle force, particularly at the knee, than females

Relationships between Obesity, Cardiorespiratory Fitness, and Cardiovascular Function

Background. Obesity and low cardiorespiratory fitness (CRF) have been shown to independently increase the risk of CVD mortality. The aim of this study was to investigate the relationship between CRF, body fatness and markers of arterial function. Method and Results. Obese (9 male, 18 female; BMI 35.3 ± 0.9 kg·m−2) and lean (8 male, 18 female; BMI 22.5 ± 0.3 kg·m−2) volunteers were assessed for body composition (DXA), cardiorespiratory fitness (predicted V˙O2max), blood pressure (BP), endothelial vasodilatator function (FMD), and arterial compliance (AC) (via radial artery tonometry). The obese group had more whole body fat and abdominal fat (43.5 ± 1.2% versus 27.2 ± 1.6%; P < .001 and 48.6 ± 0.9% versus 28.9 ± 1.8%; P < .001, resp.), and lower FMD (3.2 ± 0.4% versus 5.7 ± 0.7%; P < .01) than the lean subjects, but there was no difference in AC. AC in large arteries was positively associated with CRF (R = 0.5; P < .01) but not with fatness. Conclusion. These results indicate distinct influences of obesity and CRF on blood vessel health. FMD was impaired with obesity, which may contribute to arterial and metabolic dysfunction. Low CRF was associated with reduced elasticity in large arteries, which could result in augmentation of aortic afterload

The Impact of Including Carbonyl Iron Particles on the Melt Electrowriting Process

Melt electrowriting, a high-resolution additive manufacturing technique, is used in this study to process a magnetic polymer-based blend for the first time. Carbonyl iron (CI) particles homogenously distribute into poly(vinylidene fluoride) (PVDF) melts to result in well-defined, highly porous structures or scaffolds comprised of fibers ranging from 30 to 50 mu m in diameter. This study observes that CI particle incorporation is possible up to 30 wt% without nozzle clogging, albeit that the highest concentration results in heterogeneous fiber morphologies. In contrast, the direct writing of homogeneous PVDF fibers with up to 15 wt% CI is possible. The fibers can be readily displaced using magnets at concentrations of 1 wt% and above. Combined with good viability of L929 CC1 cells using Live/Dead imaging on scaffolds for all CI concentrations indicates that these formulations have potential for the usage in stimuli-responsive applications such as 4D printing.Peer reviewe

Melt electrowriting of poly(vinylidene fluoride-co-trifluoroethylene) : Melt electrowriting of poly(vinylidene fluoride-co-trifluoroethylene)

Poly(vinylidene fluoride-co-trifluoroethylene) (P(VDF-co-TrFE)) is an electroactive polymer with growing interest for applications in biomedical materials and flexible electronics. In this study, a solvent-free additive manufacturing technique called melt electrowriting (MEW) has been utilized to fabricate well-defined microperiodic structures of the copolymer (P(VDF-co-TrFE)). MEW of the highly viscous polymer melt was initiated using a heated collector at temperatures above 120 °C and required remarkably slow collector speeds below 100 mm min−1. The fiber surface morphology was affected by the collector speed and an increase in β-phase was observed for scaffolds compared to the unprocessed powder. Videography shows vibrations of the P(VDF-co-TrFE) jet previously unseen during MEW, probably due to repeated charge buildup and discharge. Furthermore, piezo-force microscopy measurements demonstrated the electromechanical response of MEW-fabricated fibers. This research therefore achieves the melt electrohydrodynamic processing of fibers with micrometer resolution into defined structures with an important electroactive polymer. © 2021 The Authors. Polymer International published by John Wiley & Sons Ltd on behalf of Society of Industrial Chemistry.Peer reviewe