This work shows the ability to reversibly modulate the hydrophilicity of the hydrogels doped with iron oxide nanoparticles (MNPs) in a noninvasive way when exposed to a cyclic variation of the ...intensity (ON/OFF) of an external magnetic field. A reversible switching of surface contact angles was observed for magnetic PVA hydrogels when exposed to consecutive variation of the magnetic field intensity between 0 and 0.08 T. Motivated by the magnetic dependence of the hydrophilicity of these hybrid hydrogels, the impact of the magnetic field on protein sorption was also evaluated. The noninvasive regulation of protein sorption-released mechanisms was achieved by ON/OFF magnetic field switches, suggesting the possible influence of magnetic-induced hydrogel shrinking effect and changes of surface wettability on protein sorption. The capacity to magnetically modulate surface wettability and protein sorption make these magnetic hydrogels promising candidates for development of functional devices for tissue engineering, drug release applications, or biosensor systems, where the control of protein sorption and mobility are essential steps to improve the efficiency of these processes.
Mesenchymal stem/stromal cells (MSCs) have been increasingly used in clinical trials for low-back pain (LBP) and intervertebral disc (IVD) degeneration with promising results. Their action mechanisms ...are not fully understood, but they reduce IVD pro-inflammatory markers in a pro-inflammatory/degenerative IVD microenvironment. In this study the therapeutic potential of the MSC secretome, as an alternative cell-free approach for treating degenerated IVDs, was examined. Human bone marrow-derived MSC secretome (MSCsec) was collected after 48 h of preconditioning in IL-1β (10 ng/mL) and low oxygen (6 % O2), mimicking the degenerative IVD. IL-1β-pre-conditioning of MSCs increased secretion of pro-inflammatory markers hIL-6, hIL-8, hMCP-1, etc. The therapeutic effect of MSCsec was tested in a pro-inflammatory/degenerative IVD ex vivo model. MSCsec down-regulated IVD gene expression of pro-inflammatory cytokines (bIL-6, bIL-8) and matrix degrading enzyme bMMP1, while bMMP3 and bTIMP2 were up-regulated, at 48 h. After 14 d, MSCsec-treated IVDs revealed increased aggrecan deposition, although no differences in other ECM components were observed. Protein analysis of the MSCsec-treated IVD supernatant revealed a significant increase of CXCL1, MCP-1, MIP-3α, IL-6, IL-8 and GRO α/β/γ (related to TNF, NOD-like receptor and neutrophil chemotaxis signalling), and a decrease of IFN-γ, IL-10, IL-4, IL-5 and TNF-α (associated with T-cell receptor signalling). MSCsec-treated IVD supernatants did not promote angiogenesis and neurogenesis in vitro. Overall, MSCsec can be a safe therapeutic approach, presenting a strong immunomodulatory role in degenerated IVD while potentiating aggrecan deposition, which can open new perspectives on the use of MSCsec as a cell-based/ cell-free therapeutic approach to LBP.
This work presents the development of multivariate statistically-based models for monitoring several key performance parameters of membrane bioreactors (MBR) for wastewater treatment. This ...non-mechanistic approach enabled the deconvolution of 2D fluorescence spectroscopy data, a powerful technique that has previously been shown to capture important information regarding MBR performance. Projection to latent structure (PLS) modelling was used to integrate 2D fluorescence data, after compression through parallel factor analysis (PARAFAC), with operation and analytical data to describe an MBR fouling indicator (transmembrane pressure, TMP), five descriptors of the effluent quality (total COD, soluble COD, concentration of nitrite and nitrate, total nitrogen and total phosphorus in the permeate) and the biomass concentration in the bioreactor (MLSS). A multilinear correlation was successfully established for TMP, CODtp and CODsp, whereas the optimised models for the remaining outputs included quadratic and interaction terms of the compressed 2D fluorescence matrices. Additionally, the coefficients of the optimised models revealed important contributions of some of the input parameters to the modelled outputs. This work demonstrates the applicability of 2D fluorescence and statistically-based models to simultaneously monitor multiple key MBR performance parameters with minimal analytical effort. This is a promising approach to facilitate the implementation of MBR technology for wastewater treatment.
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► Statistically-based models were developed for monitoring a membrane bioreactor. ► 2D fluorescence data was incorporated in addition to operation and analytic data. ► PLS modelling was applied, after PARAFAC compression of fluorescence data. ► Indicators of permeability, effluent quality and biomass were successfully modelled. ► Multiple performance descriptors can be simultaneously monitored with few analysis.
The aim is to determine the prevalence of active infection by herpes simplex virus type 2 (HSV‐2) among Mexican women with high‐risk human papillomavirus (HR‐HPV) cervical infection, recruited from ...public gynecology and colposcopy services. In a cross‐sectional study, HSV‐2 antibodies, HSV‐2 DNA, and HR‐HPV DNA were quantified. Significant differences in HSV‐2 seroprevalence and HSV‐2 active infection rates were found between negative and positive HR‐HPV cases. HSV‐2 seroprevalence was 28.15% and 16.1% (P = .0001), while HSV‐2 active infection rates were 6.83% and 0.62% (P = .001) for positive and negative HR‐HPV groups, respectively. The risk of HSV‐2 seropositivity was 1.7 times greater for HR‐HPV‐positive cases (P = .02). Similarly, HR‐HPV‐positive cases were nine times more likely to have an HSV‐2 active infection than HR‐HPV‐negative cases (P = .03). High HSV‐2/h‐HPV coinfection rates were observed among women recruited from public gynecology and colposcopy services. The main factors related to an HSV‐2 active infection are a history of risky sexual behavior and HR‐HPV infection. The prevalence of HSV‐2 active infection among positive HR‐HPV subjects indicate that these infections constitute an important group of STIs in Mexico.
Research Highlights
The current study included data from seroprevalence of HSV‐2 infection and the rate of HSV‐2 active infection among women recruited from public gynecology and colposcopy services and determined the demographic, clinical, and sexual behavior characteristics associated to HSV‐2 seroprevalence and active infection.
This study provides information about High HSV‐2/HR‐HPV coinfection rates are observed among women recruited from public gynecology and colposcopy services indicating that these infections constitute an important group of sexually‐transmitted infections in Mexico.
The growing prevalence of vascular diseases worldwide has emphasized the need for novel tissue-engineered options concerning the development of vascularized 3D constructs. This study reports, for the ...first time, the use of external magnetic fields to stimulate mesenchymal stromal cells (MSCs) to increase the production of vascular endothelial growth factor-A (VEGF-A). Polyvinylalcohol and gelatin-based scaffolds, containing iron oxide nanoparticles, were designed for optimal cell magnetic stimulation. While the application of static magnetic fields over 24 h did not impact on MSCs proliferation, viability and phenotypic identity, it significantly increased the production of VEGF-A and guided MSCs morphology and alignment. The ability to enhance MSCs angiogenic potential was demonstrated by the increase in the number of new vessels formed in the presence of MSCs conditioned media through in vitro and in vivo models. Ultimately, this study uncovers the potential to manipulate cellular processes through short-term magnetic stimulation.
This work explores the unique features of magnetic-responsive hydrogels to obtain liposomal hydrogel delivery platforms capable of precise magnetically modulated drug release based on the mechanical ...responses of these hydrogels when exposed to an external magnetic field. Magnetic-responsive liposomal hydrogel delivery systems were prepared by encapsulation of 1,2-dipalmitoyl-sn-glycero-3-phosphocoline (DPPC) multilayered vesicles (MLVs) loaded with ferulic acid (FA), i.e., DPPC:FA liposomes, into gelatin hydrogel membranes containing dispersed iron oxide nanoparticles (MNPs), i.e., magnetic-responsive gelatin. The FA release mechanisms and kinetics from magnetic-responsive liposomal gelatin were studied and compared with those obtained with conventional drug delivery systems, e.g., free liposomal suspensions and hydrogel matrices, to access the effect of liposome entrapment and magnetic field on FA delivery. FA release from liposomal gelatin membranes was well described by the Korsmeyer-Peppas model, indicating that FA release occurred under a controlled diffusional regime, with or without magnetic stimulation. DPPC:FA liposomal gelatin systems provided smoother controlled FA release, relative to that obtained with the liposome suspensions and with the hydrogel platforms, suggesting the promising application of liposomal hydrogel systems in longer-term therapeutics. The magnetic field, with low intensity (0.08 T), was found to stimulate the FA release from magnetic-responsive liposomal gelatin systems, increasing the release rates while shifting the FA release to a quasi-Fickian mechanism. The magnetic-responsive liposomal hydrogels developed in this work offer the possibility to magnetically activate drug release from these liposomal platforms based on a non-thermal related delivery strategy, paving the way for the development of novel and more efficient applications of MLVs and liposomal delivery systems in biomedicine.
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•MILs are “2nd-Gen” magnetic liquids without dispersed magnetic particles.•Uniform tangential magnetic fields produce magnetic hydraulic pressures in MILs.•FHD-Bernoulli eq. predicts ...the magnetic hydraulic pressure or head (>900Pa or 6cm).•Phenomena directly related to magnetic susceptibility and the field strength squared.•Phenomena could complicate research of MILs as reaction media or separation agents.
Magnetic Ionic Liquid (MILs), novel magnetic molecules that form “pure magnetic liquids,” will follow the Ferrohydrodynamic Bernoulli Relationship. Based on recent literature, the modeling of this fluid system is an open issue and potentially controversial.
We imposed uniform magnetic fields parallel to MIL/air interfaces where the capillary forces were negligible, the Quincke Problem. The size and location of the bulk fluid as well as the size and location of the fluid/air interface inside of the magnetic field were varied. MIL properties varied included the density, magnetic susceptibility, chemical structure, and magnetic element.
Uniform tangential magnetic fields pulled the MILs up counter to gravity. The forces per area were not a function of the volume, the surface area inside of the magnetic field, or the volume displacement. However, the presence of fluid/air interfaces was necessary for the phenomena. The Ferrohydrodynamic Bernoulli Relationship predicted the phenomena with the forces being directly related to the fluid’s volumetric magnetic susceptibility and the square of the magnetic field strength. emimFeCl4 generated the greatest hydraulic head (64-mm or 910Pa at 1.627Tesla). This work could aid in experimental design, when free surfaces are involved, and in the development of MIL applications.
This article presents the synthesis of poly(methacrylic acid)‐b‐poly(methyl methacrylate) diblock copolymer via polymerization‐induced self‐assembly in the presence of iron‐oxide nanoparticles. ...Detailed phase diagrams with and without inorganic nanoparticles were constructed. Scanning transmission electron microscopy and energy dispersive X‐ray photometry studies confirme the decoration of the polymeric nanoparticles with the iron‐oxide nanoparticles. These hybrid nanoparticles were used to prepare porous thin film membranes by spin coating. Finally, the magneto‐responsive properties of the membranes were assessed using water filtration tests in the presence and absence of a magnetic field.
Iron‐oxide‐decorated PMAA‐b‐PMMA nanoparticles are prepared via polymerization‐induced self‐assembly and the influence of presence of magnetic iron‐oxide nanoparticles on the phase diagram is investigated. Thin‐film membranes made from these decorated nanoparticles show magnetic character.
The control of angiogenesis has the potential to be used for regulation of several pathological and physiological processes, which can be instrumental on the development of anticancer and wound ...healing therapeutical approaches. In this study, mesenchymal stem/stromal cells (MSCs) were seeded on magnetic-responsive gelatin, with or without heparin functionalization, and exposed to a static 0.08 T magnetic field (MF), for controlling their anti-inflammatory and angiogenic activity, with the aim of accelerating tissue healing. For the first time, it was examined how the amount of heparin and magnetic nanoparticles (MNPs) distributed on gelatin scaffolds affected the mechanical properties of the hydrogels and the morphology, proliferation, and secretome profiling of MSCs. The findings demonstrated that the addition of MNPs and heparin affects the hydrogel swelling capacity and renders distinct MSC proliferation rates. Additionally, MF acts as a topographical cue to guide MSCs alignment and increases the level of expression of specific genes and proteins that promote angiogenesis. The results also suggested that the presence of higher amounts of heparin (10 μg/cm3) interferes with the secretion and limits the capacity of angiogenic factors to diffuse through the hydrogel and into the culture medium. Ultimately, this study shows that acellular heparinized hydrogels efficiently retain the angiogenic growth factors released by magnetically stimulated MSCs thus rendering superior wound contraction (55.8% ± 0.4%) and cell migration rate (49.4% ± 0.4%), in comparison to nonheparinized hydrogels (35.2% ± 0.7% and 37.8% ± 0.7%, respectively). Therefore, these heparinized magnetic hydrogels can be used to facilitate angiogenesis in various forms of tissue damage including bone defects, skin wounds, and cardiovascular diseases, leading to enhanced tissue regeneration.
The main objective of the present study was to investigate the use of in situ 2D fluorometry for monitoring key bioprocess variables in mammalian cell cultures, namely the concentration of viable ...cells and the concentration of recombinant proteins. All studies were conducted using a recombinant Baby Hamster Kidney (BHK) cell line expressing a fusion glycoprotein IgG1-IL2 cultured in batch and fed-batch modes. It was observed that the intensity of fluorescence signals in the excitation/emission wavelength range of amino acids, vitamins and NAD(P)H changed along culture time, although the dynamics of single fluorophors could not be correlated with the dynamics of the target state variables. Therefore, multivariate chemometric modeling was adopted as a calibration methodology. 2D fluorometry produced large volumes of redundant spectral data, which were first filtered by principal components analysis (PCA). Then, a partial least squares (PLS) regression was applied to correlate the reduced fluorescence maps with the target state variables. Two validation strategies were used to evaluate the predictive capacity of the developed PLS models. Accurate estimations of viable cells density (r² = 0.95; 99.2% of variance captured in the training set; r² = 0.91; 97.7% of variance captured in the validation set) and of glycoprotein concentration (r² = 0.99 and 99.7% of variance captured in the training set; r² = 0.99 and 99.3% of variance captured in the validation set) were obtained over a wide range of reactor operation conditions. The results presented herein confirm that 2D fluorometry constitutes a reliable methodology for on-line monitoring of viable cells and recombinant protein concentrations in mammalian cell cultures. Biotechnol. Bioeng. 2009;102: 1098-1106.