Mouse embryo assay to evaluate polydimethylsiloxane (PDMS) embryo-toxicity

In vitro embryo culture to support In Vitro Fertilization (IVF) procedures is a well-established but still critical technique. In the last decade first attempts to use microfluidic devices in IVF have shown positive results, enabling to control the culture conditions and to preserve the quality of the embryos during their development. In this study we completed an industry standard mouse embryo assay (MEA) to exclude potential toxic effects of PDMS

Organs-on-chip models of the female reproductive system

Microfluidic-based technology attracts great interest in cell biology and medicine, in virtue of the ability to better mimic the in vivo cell microenvironment compared to conventional macroscale cell culture platforms. Recent Organs-on-chip (OoC) models allow to reproduce in vitro tissue and organ-level functions of living organs and systems. These models have been applied for the study of specific functions of the female reproductive tract, which is composed of several organs interconnected through intricate endocrine pathways and communication mechanisms. To date, a disease and toxicology study of this system has been difficult to perform. Thus, there is a compelling need to develop innovative platforms for the generation of disease model and for performing drug toxicity/screening in vitro studies. This review is focused on the analysis of recently published OoC models that recreate pathological and physiological characteristics of the female reproductive organs and tissues. These models aim to be used to assess changes in metabolic activity of the specific cell types and the effect of exposure to hormonal treatment or chemical substances on some aspects of reproduction and fertility. We examined these models in terms of device specifications, operating procedures, accuracy for studying the biochemical and functional activity of living tissues and the paracrine signalling that occurs within the different tissues. These models represent a powerful tool for understanding important diseases and syndromes affecting women all around the world. Immediate adoption of these models will allow to clarify diseases, causes and adverse events occurring during pregnancy such as pre-eclampsia, infertility or preterm birth, endometriosis and infertility

The WINPack 1 a novel wearable system for heart rate and vital signs monitoring

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Ultrasonographic mound height as predictor of vesicoureteral reflux resolution after endoscopic treatment in children

Purpose: Endoscopic dextranomer/hyaluronic acid copolymer (Dx/HA) injection is a safe and efficacious treatment option for vesicoureteral reflux (VUR) in children. Endoscopic appearance, hydrodistention and amount of injected Dx/HA have been demonstrated not to be reliable predictors of outcome. Aim of this study was to evaluate Dx/HA mounds on ultrasound scans (US) and find out any eventual correlation with reflux resolution. Methods: We selected patients treated with endoscopic injection for moderate to high VUR, renal scaring or repeated infections under antibiotic prophylaxis. Success was defined by absence of VUR at control 3. months after surgery; at 3. months we also measured mound height ultrasonographically. Results: We considered a total of 32 children (15 male, 17 female; 53 ureters) with a median age of 3. years (±. 24. months). Overall success rate was 77% per ureter. Success rate correlates directly with age and inversely with VUR grade. Mound height is the major predictive parameter for reflux resolution (sensitivity 100%, specificity 65.9%); mean mound heights of success-group vs. persistence-of-reflux group were 9.97. ±. 1.61. mm and 7.29. ±. 1.74. mm respectively (p. <. 0.0005). Conclusion: A mound measuring at least 9.8. mm at post-operative US scan is a predictor of reflux resolution. Age and grade also seems to influence success rate

Evaluation of friction enhancement through soft polymer micro-patterns in active capsule endoscopy

Capsule endoscopy is an emerging field in medical technology. Despite very promising innovations, some critical issues are yet to be addressed, such as the management and possible exploitation of the friction in the gastrointestinal environment in order to control capsule locomotion more actively. This paper presents the fabrication and testing of bio-inspired polymeric micro-patterns, which are arrays of cylindrical pillars fabricated via soft lithography. The aim of the work is to develop structures that enhance the grip between an artificial device and the intestinal tissue, without injuring the mucosa. In fact, the patterns are intended to be mounted on microfabricated legs of a capsule robot that is able to move actively in the gastrointestinal tract, thus improving the robot’s traction ability. The effect of micro-patterned surfaces on the leg-slipping behaviour on colon walls was investigated by considering both different pillar dimensions and the influence of tissue morphology. Several in vitro tests on biological samples demonstrated that micro-patterns of pillars made from a soft polymer with an aspect ratio close to 1 enhanced friction by 41.7% with regard to flat surfaces. This work presents preliminary modelling of the friction and adhesion forces in the gastrointestinal environment and some design guidelines for endoscopic devices

Assessment of the Fitbit Charge 2 for monitoring heart rate

Fitness trackers are devices or applications for monitoring and tracking fitness-related metrics such as distance walked or run, calorie consumption, quality of sleep and heart rate. Since accurate heart rate monitoring is essential in fitness training, the objective of this study was to assess the accuracy and precision of the Fitbit Charge 2 for measuring heart rate with respect to a gold standard electrocardiograph. Fifteen healthy participants were asked to ride a stationary bike for 10 minutes and their heart rate was simultaneously recorded from each device. Results showed that the Fitbit Charge 2 underestimates the heart rate. Although the mean bias in measuring heart rate was a modest -5.9 bpm (95% CI: -6.1 to -5.6 bpm), the limits of agreement, which indicate the precision of individual measurements, between the Fitbit Charge 2 and criterion measure were wide (+16.8 to -28.5 bpm) indicating that an individual heart rate measure could plausibly be underestimated by almost 30 bpm

Adhesion and proliferation of skeletal muscle cells on single layer poly(lactic acid) ultra-thin films

An increasing interest in bio-hybrid systems and cell-material interactions is evident in the last years. This leads towards the development of new nano-structured devices and the assessment of their biocompatibility. In the present study, the development of free-standing single layer poly(lactic acid) (PLA) ultra-thin films is described, together with the analysis of topography and roughness properties. The biocompatibility of the PLA films has been tested in vitro, by seeding C2C12 skeletal muscle cells, and thus assessing cells shape, density and viability after 24, 48 and 72 h. The results show that free-standing flexible PLA nanofilms represent a good matrix for C2C12 cells adhesion, spreading and proliferation. Early differentiation into myotubes is also allowed. The biocompatibility of the novel ultra-thin films as substrates for cell growth promotes their application in the fields of regenerative medicine, muscle tissue engineering, drug delivery, and-in general-in the field of bio-hybrid devices

Potential of Manuka Honey as a Natural Polyelectrolyte to Develop Biomimetic Nanostructured Meshes With Antimicrobial Properties

The use of antibiotics has been the cornerstone to prevent bacterial infections; however, the emergency of antibiotic-resistant bacteria is still an open challenge. This work aimed to develop a delivery system for treating soft tissue infections for: (1) reducing the released antimicrobial amount, preventing drug-related systemic side effects; (2) rediscovering the beneficial effects of naturally derived agents; and (3) preserving the substrate functional properties. For the first time, Manuka honey (MH) was proposed as polyelectrolyte within the layer-by-layer assembly. Biomimetic electrospun poly(εcaprolactone) meshes were treated via layer-by-layer assembly to obtain a multilayered nanocoating, consisting of MH as polyanion and poly-(allylamine-hydrochloride) as polycation. Physicochemical characterization demonstrated the successful nanocoating formation. Different cell lines (human immortalized and primary skin fibroblasts, and primary endothelial cells) confirmed positively the membranes cytocompatibility, while bacterial tests using Gram-negative and Gram-positive bacteria demonstrated that the antimicrobial MH activity was dependent on the concentration used and strains tested

The use of a novel microfluidic culture device and predictive metabolic profiling as a means to improve murine embryo developmental competence in vitro

Successful embryo development in vitro is directly dependent on the provision of an optimal culture environment that supports coordinated embryonic cell division, metabolism, and genetic and epigenetic development. A number of attempts have been made over recent years to use microfluidic devices in IVF as a means to control the culture environment and so improve embryo developmental competence (quality) in vitro. In this study we have designed, engineered and tested a novel microfluidic device for the in vitro production of murine embryos from the 1 cell zygote stage to the blastocyst stage. Soft lithography was used to prepare microfluidic devices in polydimethylsiloxane (PDMS). The microfluidic device consists of a 400 nL circular chamber (radius 750 mm) where 10 embryos can be loaded, kept in static culture for the full period of culture and visualized by optical and fluorescent microscopy. A series of 2 experiments were conducted to evaluate the efficacy of our microfluidic device for mouse embryo culture. Cryopreserved, IVF-derived, mouse embryos of strain C57BL/6N, provided by MRC Harwell, UK were cultured in KSOM media. Microfluidic culture was used in conjunction with non-invasive analysis of glucose (G), pyruvate (P) and lactate (L) metabolism in spent zygote culture media as a means to improve embryo quality. In both experimental series, data from microfluidic cultures were compared to equivalent end point analyses of control embryos grown in conventional microdrop cultures under oil. Experiment 1: 2 cell embryos were thawed and cultured in groups of 8-10 in microfluidic devices (n=46) or 10µl control (n=32) drops for 3 days at 37oC under 5%CO2/5%O2/N2 balance. Embryos were removed to individual culture drops for 24h for analysis of energy substrate turnover using the method of Guerif et al. (PLOS ONE, 2013) followed by transfer to fibronectin-coated dishes for assessment of attachment and outgrowth according to the method of Hannan et al. (Endocrinology, 152 (12), p4948-4956, 2011). Blastocyst grade, hatching, attachment, outgrowth rates, and pyruvate and glucose consumption were assessed and were similar between device and control groups (P>0.05). However, lactate output was significantly reduced following device culture vs controls (4.1±0.8 vs 1.4±0.3 pmol/embryo/hr, P=<0.0001). GPL metabolism did not predict embryo attachment or outgrowth in either culture environment. Experiment 2: 1 cell zygotes were cultured individually overnight for analysis of GPL metabolism and assigned to culture groups based on pyruvate consumption, with 1 device and 1 microdrop group per tertile per culture with 10 embryos per group (total n=60 device and n=60 control). Following group culture, individual blastocyst pyruvate consumption was reduced (5.4±2.2 vs 12±1.5 pmol/embryo/hr, P=<0.0001). Pyruvate consumption tertile was unaffected by device culture. Device culture was non-toxic and did not affect embryo development. However, blastocyst pyruvate consumption and lactate output were reduced compared to controls. This may suggest microfluidic culture can be utilised to achieve a controlled, moderate metabolic phenotype, reducing variation between embryo metabolism