An in vitro experimental model to predict the mechanical behaviour of macroporous scaffolds implanted in articular cartilage

A model is proposed to assess mechanical behaviour of tissue engineering scaffolds and predict their performance in vivo during tissue regeneration. To simulate the growth of tissue inside the pores of the scaffold, the scaffold is swollen with a Poly (Vinyl alcohol) solution and subjected to repeated freezing and thawing cycles. In this way the Poly (Vinyl alcohol) becomes a gel whose stiffness increases with the number of freezing and thawing cycles. Mechanical properties of the construct immersed in water are shown to be determined, in large extent, by the water mobility constraints imposed by the gel filling the pores. This is similar to the way that water mobility determines mechanical properties of highly hydrated tissues, such as articular cartilage. As a consequence, the apparent elastic modulus of the scaffold in compression tests is much higher than those of the empty scaffold or the gel. Thus this experimental model allows assessing fatigue behaviour of the scaffolds under long-term dynamic loading in a realistic way, without recourse to animal experimentation.The UPV group acknowledges the support of the Spanish MICINN through project MAT2010-21611-C03-01. CIBER-BBN is an initiative funded by the VI National R&D&i Plan 2008-2011, Iniciativa Ingenio 2010, Consolider Program. CIBER Actions are financed by the Instituto de Salud Carlos III with assistance from the European Regional Development Fund. The authors thank the microscopy service of Universitat Politecnica de Valencia for useful help and advice and Ricardo Perez Feito for technical assistance in the experimental set up.Vikingsson, LKA.; Gallego Ferrer, G.; Gómez-Tejedor, JA.; Gómez Ribelles, JL. (2014). An in vitro experimental model to predict the mechanical behaviour of macroporous scaffolds implanted in articular cartilage. Journal of the Mechanical Behavior of Biomedical Materials. 32:125-131. https://doi.org/10.1016/j.jmbbm.2013.12.024S1251313

Dipolar interactions and anisotropic magnetoresistance in metallic granular systems

We revisit the theory of magnetoresistance for a system of nanoscopic magnetic granules in metallic matrix. Using a simple model for the spin dependent perturbation potential of the granules, we solve Boltzmann equation for the spin dependent components of the non equilibrium electronic distribution function. For typical values of the geometric parameters in granular systems, we find a peculiar structure of the distribution function of conduction electrons, which is at variance with the two-current model of conduction in inhomogeneous systems. Our treatment explicitly includes the effects of dipolar correlations yielding a magnetoresistance ratio which contains, in addition to the term proportional to the square of uniform magnetization (), a weak anisotropic contribution depending on the angle between electric and magnetic fields, and arising from the anisotropic character of dipolar interactions.Comment: 9 pages, 2 figures, accepted in PR

Prediction of the in vivo mechanical behavior of biointegrable acrylic macroporous scaffolds

[EN] This study examines a biocompatible scaffold series of random copolymer networks P(EA-HEA) made of Ethyl Acrylate, EA, and 2-Hydroxyl Ethyl Acrylate, HEA. The P(EA-HEA) scaffolds have been synthesized with varying crosslinking density and filled with a Poly(Vinyl Alcohol), PVA, to mimic the growing cartilaginous tissue during tissue repair. In cartilage regeneration the scaffold needs to have sufficient mechanical properties to sustain the compression in the joint and, at the same time, transmit mechanical signals to the cells for chondrogenic differentiation. Mechanical tests show that the elastic modulus increases with increasing crosslinking density of P(EA-HEA) scaffolds. The water plays an important role in the mechanical behavior of the scaffold, but highly depends on the crosslinking density of the proper polymer. Furthermore, when the scaffold with hydrogel is tested it can be seen that the modulus increases with increasing hydrogel density. Even so, the mechanical properties are inferior than those of the scaffolds with water filling the pores. The hydrogel inside the pores of the scaffolds facilitates the expulsion of water during compression and lowers the mechanical modulus of the scaffold. The P(EA-HEA) with PVA shows to be a good artificial cartilage model with mechanical properties close to native articular cartilage.This work was funded by the Spanish Ministry of Economy and Competitiveness (MINECO) through the project MAT2013-46467-C4-1-R (including the FEDER financial support). CIBER-BBN is an initiative funded by the VI National R&D&i Plan 2008-2011, Iniciativa Ingenio 2010, Consolider Program. CIBER actions are financed by the Instituto de Salud Carlos III with assistance from the European Regional Development Fund. The authors acknowledge the assistance and advice of Electron Microscopy Service of the UPV.Vikingsson, L.; Antolinos Turpín, CM.; Gómez-Tejedor, JA.; Gallego Ferrer, G.; Gómez Ribelles, JL. (2016). Prediction of the in vivo mechanical behavior of biointegrable acrylic macroporous scaffolds. Materials Science and Engineering: C. 61:651-658. https://doi.org/10.1016/j.msec.2015.12.068S6516586

The feasibility of testing whether Fasciola hepatica is associated with increased risk of verocytotoxin producing Escherichia coli O157 from an existing study protocol

The parasite Fasciola hepatica is a major cause of economic loss to the agricultural community worldwide as a result of morbidity and mortality in livestock, including cattle. Cattle are the principle reservoir of verocytotoxigenic Escherichia coli O157 (VTEC O157), an important cause of disease in humans. To date there has been little empirical research on the interaction between F. hepatica and VTEC O157. It is hypothesised that F. hepatica, which is known to suppress type 1 immune responses and induce an anti-inflammatory or regulatory immune environment in the host, may promote colonisation of the bovine intestine with VTEC O157. Here we assess whether it is statistically feasible to augment a prospective study to quantify the prevalence of VTEC O157 in cattle in Great Britain with a pilot study to test this hypothesis. We simulate data under the framework of a mixed-effects logistic regression model in order to calculate the power to detect an association effect size (odds ratio) of 2. In order to reduce the resources required for such a study, we exploit the fact that the test results for VTEC O157 will be known in advance of testing for F. hepatica by restricting analysis to farms with a VTEC O157 sample prevalence of >0% and <100%. From a total of 270 farms (mean 27 cows per farm) that will be tested for VTEC O157, power of 87% can be achieved, whereby testing of F. hepatica would only be necessary for an expected 50 farms, thus considerably reducing costs. Pre-study sample size calculations are an important part of any study design. The framework developed here is applicable to the study of other co-infections

A patient-derived explant (PDE) model of hormone-dependent cancer

Breast and prostate cancer research to date has largely been predicated on the use of cell lines in vitro or in vivo. These limitations have led to the development of more clinically relevant models, such as organoids or murine xenografts that utilize patient-derived material; however, issues related to low take rate, long duration of establishment, and the associated costs constrain use of these models. This study demonstrates that ex vivo culture of freshly resected breast and prostate tumor specimens obtained from surgery, termed patient-derived explants (PDEs), provides a high-throughput and cost-effective model that retains the native tissue architecture, microenvironment, cell viability, and key oncogenic drivers. The PDE model provides a unique approach for direct evaluation of drug responses on an individual patient's tumor, which is amenable to analysis using contemporary genomic technologies. The ability to rapidly evaluate drug efficacy in patient-derived material has high potential to facilitate implementation of personalized medicine approaches.Margaret M. Centenera, Theresa E. Hickey, Shalini Jindal, Natalie K. Ryan, Preethi Ravindranathan, Hisham Mohammed, Jessica L. Robinson, Matthew J. Schiewer, Shihong Ma, Payal Kapur, Peter D. Sutherland, Clive E. Hoffmann, Claus G. Roehrborn, Leonard G. Gomella, Jason S. Carroll, Stephen N. Birrell, Karen E. Knudsen, Ganesh V. Raj, Lisa M. Butler, Wayne D. Tille

Author Correction: A chickpea genetic variation map based on the sequencing of 3,366 genomes

In Extended Data Fig. 1 of this Article, the labels ‘Market class’ and ‘Biological status’ were inadvertently swapped. In the corresponding figure legend, “Track 1: Biological status; Track 2: Market class;” should have been “Track 1: Market class; Track 2: Biological status;”. The original Article has been corrected online

Sensitization in transplantation: Assessment of Risk 2022 Working Group meeting report

The Sensitization in Transplantation: Assessment of Risk workgroup is a collaborative effort of the American Society of Transplantation and the American Society of Histocompatibility and Immunogenetics that aims at providing recommendations for clinical testing, highlights gaps in current knowledge, and proposes areas for further research to enhance histocompatibility testing in support of solid organ transplantation. This report provides updates on topics discussed by the previous Sensitization in Transplantation: Assessment of Risk working groups and introduces 2 areas of exploration: non-human leukocyte antigen antibodies and utilization of human leukocyte antigen antibody testing measurement to evaluate the efficacy of antibody-removal therapies

Genotoxic effect induced by hydrogen peroxide in human hepatoma cells using comet assay

Background: Hydrogen peroxide is a common reactive oxygen intermediate generated by variousforms of oxidative stress. Aims: The aim of this study was to investigate the DNA damage capacity ofH2O2 in HepG2 cells. Methods: Cells were treated with H2O2 at concentrations of 25 μM or 50 μM for5 min, 30 min, 40 min, 1 h or 24 h in parallel. The extent of DNA damage was assessed by the cometassay. Results: Compared to the control, DNA damage by 25 μM and 50 μM H2O2 increasedsignificantly with increasing incubation time up to 1 h, but it was not increased at 24 h. Conclusions:Our Findings confirm that H2O2 is a typical DNA damage inducing agent and thus is a good modelsystem to study the effects of oxidative stress. DNA damage in HepG2 cells increased significantlywith H2O2 concentration and time of incubation but later decreased likely due to DNA repairmechanisms and antioxidant enzyme