Hydrogels Based on Polyacrylamide and Calcium Alginate: Thermodynamic Compatibility of Interpenetrating Networks, Mechanical, and Electrical Properties.

The synthesis and physicochemical properties of hydrogels with interpenetrated physical and chemical networks were considered in relation to their prospective application as biomimetic materials in biomedicine and bioengineering. The study was focused on combined hydrogels based on natural polysaccharide-calcium alginate (CaAlg) and a synthetic polymer-polyacrylamide (PAAm). The series of hydrogels with varying proportions among alginate and polyacrylamide have been synthesized, and their water uptake has been characterized depending on their composition. The equilibrium swelling and re-swelling in water after drying were considered. The compatibility of alginate and polyacrylamide in the combined blend was studied by the thermodynamic approach. It showed a controversial combination of negative enthalpy of mixing among PAAm and CaAlg with positive Gibbs energy of mixing. Mechanical and electrical properties of the combined gels with double networking were studied as relevant for their prospective use as scaffolds for tissue regeneration and working bodies in actuators. The storage modulus and the loss modulus were determined in the oscillatory compression mode as a function of proportions among natural and synthetic polymers. Both moduli substantially increased with the content of CaAlg and PAAm. The electrical (Donnan) potential of hydrogels was measured using the capillary electrode technique. The Donnan potential was negative at all compositions of hydrogels, and its absolute values increased with the content of CaAlg and PAAm.

Biological Impact of γ-Fe2O3 Magnetic Nanoparticles Obtained by Laser Target Evaporation: Focus on Magnetic Biosensor Applications.

The biological activity of γ-Fe2O3 magnetic nanoparticles (MNPs), obtained by the laser target evaporation technique, was studied, with a focus on their possible use in biosensor applications. The biological effect of the MNPs was investigated in vitro on the primary cultures of human dermal fibroblasts. The effects of the MNPs contained in culture medium or MNPs already uptaken by cells were evaluated for the cases of the fibroblast's proliferation and secretion of cytokines and collagen. For the tests related to the contribution of the constant magnetic field to the biological activity of MNPs, a magnetic system for the creation of the external magnetic field (having no commercial analogues) was designed, calibrated, and used. It was adapted to the size of standard 24-well cell culture plates. At low concentrations of MNPs, uptake by fibroblasts had stimulated their proliferation. Extracellular MNPs stimulated the release of pro-inflammatory cytokines (Interleukin-6 (IL-6) and Interleukin-8 (IL-8) or chemokine (C-X-C motif) ligand 8 (CXCL8)) in a concentration-dependent manner. However, the presence of MNPs did not increase the collagen secretion. The exposure to the uniform constant magnetic field (H ≈ 630 or 320 Oe), oriented in the plane of the well, did not cause considerable changes in fibroblasts proliferation and secretion, regardless of presence of MNPs. Statistically significant differences were detected only in the levels of IL-8/CXCL8 release.

Mechanical Force Acting on Ferrogel in a Non-Uniform Magnetic Field: Measurements and Modeling.

The development of magnetoactive microsystems for targeted drug delivery, magnetic biodetection, and replacement therapy is an important task of present day biomedical research. In this work, we experimentally studied the mechanical force acting in cylindrical ferrogel samples due to the application of a non-uniform magnetic field. A commercial microsystem is not available for this type of experimental study. Therefore, the original experimental setup for measuring the mechanical force on ferrogel in a non-uniform magnetic field was designed, calibrated, and tested. An external magnetic field was provided by an electromagnet. The maximum intensity at the surface of the electromagnet was 39.8 kA/m and it linearly decreased within 10 mm distance from the magnet. The Ferrogel samples were based on a double networking polymeric structure which included a chemical network of polyacrylamide and a physical network of natural polysaccharide guar. Magnetite particles, 0.25 micron in diameter, were embedded in the hydrogel structure, up to 24% by weight. The forces of attraction between an electromagnet and cylindrical ferrogel samples, 9 mm in height and 13 mm in diameter, increased with field intensity and the concentration of magnetic particles, and varied within 0.1-30 mN. The model provided a fair evaluation of the mechanical forces that emerged in ferrogel samples placed in a non-uniform magnetic field and proved to be useful for predicting the deformation of ferrogels in practical bioengineering applications.

Modelling of hemodynamics in bifurcation lesions of coronary arteries before and after myocardial revascularization.

Modelling of patient-specific hemodynamics for a clinical case of severe coronary artery disease with the bifurcation stenosis was carried out with allowance for standard angiographic data obtained before and after successfully performed myocardial revascularization by stenting of two arteries. Based on a non-Newtonian fluid model and an original algorithm for fluid dynamics computation operated with a limited amount of initial data, key characteristics of blood flow were determined to analyse the features of coronary disease and the consequences of its treatment. The results of hemodynamic modelling near bifurcation sites are presented with an emphasis on physical, physiological and clinical phenomena to demonstrate the feasibility of the proposed approach. The main limitations and ways to minimize them are the subjects of discussion as well. This article is part of the theme issue 'Transport phenomena in complex systems (part 2)'.

Echogenic Advantages of Ferrogels Filled with Magnetic Sub-Microparticles.

Ultrasonic imaging of ferrogels (FGs) filled with magnetic nanoparticles does not reflect the inner structure of FGs due to the small size of particles. To determine whether larger particle size would improve the acoustic properties of FGs, biocompatible hydrogels filled with 100-400 nm iron oxide magnetic sub-microparticles with weight fraction up to 23.3% were synthesized and studied. Polymeric networks of synthesized FGs were comprised of chemically cross-linked polyacrylamide with interpenetrating physical network of natural polysaccharide-Guar or Xanthan. Cylindrical samples approximately 10 mm in height and 13 mm in diameter were immersed in a water bath and examined using medical ultrasound (8.5 MHz). The acoustic properties of FGs were characterized by the intensity of reflected echo signal. It was found that the echogenicity of sub-microparticles provides visualization not only of the outer geometry of the gel sample but of its inner structure as well. In particular, the echogenicity of FGs interior depended on the concentration of magnetic particles in the FGs network. The ultrasound monitoring of the shape, dimensions, and inner structure of FGs in the applied external magnetic field is demonstrated. It is especially valuable for the application of FGs in tissue engineering and regenerative medicine.

Magnetic Properties of Iron Oxide Nanoparticles Do Not Essentially Contribute to Ferrogel Biocompatibility.

Two series of composite polyacrylamide (PAAm) gels with embedded superparamagnetic Fe2O3 or diamagnetic Al2O3 nanoparticles were synthesized, aiming to study the direct contribution of the magnetic interactions to the ferrogel biocompatibility. The proliferative activity was estimated for the case of human dermal fibroblast culture grown onto the surfaces of these types of substrates. Spherical non-agglomerated nanoparticles (NPs) of 20-40 nm in diameter were prepared by laser target evaporation (LTE) electrophysical technique. The concentration of the NPs in gel was fixed at 0.0, 0.3, 0.6, or 1.2 wt.%. Mechanical, electrical, and magnetic properties of composite gels were characterized by the dependence of Young's modulus, electrical potential, magnetization measurements on the content of embedded NPs. The fibroblast monolayer density grown onto the surface of composite substrates was considered as an indicator of the material biocompatibility after 96 h of incubation. Regardless of the superparamagnetic or diamagnetic nature of nanoparticles, the increase in their concentration in the PAAm composite provided a parallel increase in the cell culture proliferation when grown onto the surface of composite substrates. The effects of cell interaction with the nanostructured surface of composites are discussed in order to explain the results.

Effects of Constant Magnetic Field to the Proliferation Rate of Human Fibroblasts Grown onto Different Substrates: Tissue Culture Polystyrene, Polyacrylamide Hydrogel and Ferrogels γ-Fe2O3 Magnetic Nanoparticles.

The static magnetic field was shown to affect the proliferation, adhesion and differentiation of various types of cells, making it a helpful tool for regenerative medicine, though the mechanism of its impact on cells is not completely understood. In this work, we have designed and tested a magnetic system consisting of an equidistant set of the similar commercial permanent magnets (6 × 4 assay) in order to get insight on the potential of its experimental usage in the biological studies with cells culturing in a magnetic field. Human dermal fibroblasts, which are widely applied in regenerative medicine, were used for the comparative study of their proliferation rate on tissue culture polystyrene (TCPS) and on the polyacrylamide ferrogels with 0.00, 0.63 and 1.19 wt % concentrations of γ-Fe2O3 magnetic nanoparticles obtained by the well-established technique of laser target evaporation. We used either the same batch as in previously performed but different biological experiments or the same fabrication conditions for fabrication of the nanoparticles. This adds special value to the understanding of the mechanisms of nanoparticles contributions to the processes occurring in the living systems in their presence. The magnetic field increased human dermal fibroblast cell proliferation rate on TCPS, but, at the same time, it suppressed the growth of fibroblasts on blank gel and on polyacrylamide ferrogels. However, the proliferation rate of cells on ferrogels positively correlated with the concentration of nanoparticles. Such a dependence was observed both for cell proliferation without the application of the magnetic field and under the exposure to the constant magnetic field.

Ferrogels Ultrasonography for Biomedical Applications.

Ferrogels (FG) are magnetic composites that are widely used in the area of biomedical engineering and biosensing. In this work, ferrogels with different concentrations of magnetic nanoparticles (MNPs) were synthesized by the radical polymerization of acrylamide in stabilized aqueous ferrofluid. FG samples were prepared in various shapes that are suitable for different characterization techniques. Thin cylindrical samples were used to simulate the case of targeted drug delivery test through blood vessels. Samples of larger size that were in the shape of cylindrical plates were used for the evaluation of the FG applicability as substitutes for damaged structures, such as bone or cartilage tissues. Regardless of the shape of the samples and the conditions of their location, the boundaries of FG were confidently visualized over the entire range of concentrations of MNPs while using medical ultrasound. The amplitude of the reflected echo signal was higher for the higher concentration of MNPs in the gel. This result was not related to the influence of the MNPs on the intensity of the reflected echo signal directly, since the wavelength of the ultrasonic effect used is much larger than the particle size. Qualitative theoretical model for the understanding of the experimental results was proposed while taking into account the concept that at the acoustic oscillations of the hydrogel, the macromolecular net, and water in the gel porous structure experience the viscous Stocks-like interaction.

The Contribution of Magnetic Nanoparticles to Ferrogel Biophysical Properties.

Iron oxide γ-Fe2O3 magnetic nanoparticles (MNPs) were fabricated by laser target evaporation technique (LTE) and their structure and magnetic properties were studied. Polyacrylamide (PAAm) gels with different cross-linking density of the polymer network and polyacrylamide-based ferrogel with embedded LTE MNPs (0.34 wt.%) were synthesized. Their adhesive and proliferative potential with respect to human dermal fibroblasts were studied. At the same value of Young modulus, the adhesive and proliferative activities of the human dermal fibroblasts on the surface of ferrogel were unexpectedly much higher in comparison with the surface of PAAm gel. Properties of PAAm-100 + γ-Fe2O3 MNPs composites were discussed with focus on creation of a new generation of drug delivery systems combined in multifunctional devices, including magnetic field assisted delivery, positioning, and biosensing. Although exact applications are still under development, the obtained results show a high potential of LTE MNPs to be applied for cellular technologies and tissue engineering. PAAm-100 ferrogel with very low concentration of γ-Fe2O3 MNPs results in significant improvement of the cells' compatibility to the gel-based scaffold.

Mechanical, Electrical and Magnetic Properties of Ferrogels with Embedded Iron Oxide Nanoparticles Obtained by Laser Target Evaporation: Focus on Multifunctional Biosensor Applications.

Hydrogels are biomimetic materials widely used in the area of biomedical engineering and biosensing. Ferrogels (FG) are magnetic composites capable of functioning as magnetic field sensitive transformers and field assisted drug deliverers. FG can be prepared by incorporating magnetic nanoparticles (MNPs) into chemically crosslinked hydrogels. The properties of biomimetic ferrogels for multifunctional biosensor applications can be set up by synthesis. The properties of these biomimetic ferrogels can be thoroughly controlled in a physical experiment environment which is much less demanding than biotests. Two series of ferrogels (soft and dense) based on polyacrylamide (PAAm) with different chemical network densities were synthesized by free-radical polymerization in aqueous solution with N,N'-methylene-diacrylamide as a cross-linker and maghemite Fe2O3 MNPs fabricated by laser target evaporation as a filler. Their mechanical, electrical and magnetic properties were comparatively analyzed. We developed a giant magnetoimpedance (MI) sensor prototype with multilayered FeNi-based sensitive elements deposited onto glass or polymer substrates adapted for FG studies. The MI measurements in the initial state and in the presence of FG with different concentrations of MNPs at a frequency range of 1-300 MHz allowed a precise characterization of the stray fields of the MNPs present in the FG. We proposed an electrodynamic model to describe the MI in multilayered film with a FG layer based on the solution of linearized Maxwell equations for the electromagnetic fields coupled with the Landau-Lifshitz equation for the magnetization dynamics.

Polyacrylamide Ferrogels with Magnetite or Strontium Hexaferrite: Next Step in the Development of Soft Biomimetic Matter for Biosensor Applications.

Magnetic biosensors are an important part of biomedical applications of magnetic materials. As the living tissue is basically a "soft matter." this study addresses the development of ferrogels (FG) with micron sized magnetic particles of magnetite and strontium hexaferrite mimicking the living tissue. The basic composition of the FG comprised the polymeric network of polyacrylamide, synthesized by free radical polymerization of monomeric acrylamide (AAm) in water solution at three levels of concentration (1.1 M, 0.85 M and 0.58 M) to provide the FG with varying elasticity. To improve FG biocompatibility and to prevent the precipitation of the particles, polysaccharide thickeners-guar gum or xanthan gum were used. The content of magnetic particles in FG varied up to 5.2 wt % depending on the FG composition. The mechanical properties of FG and their deformation in a uniform magnetic field were comparatively analyzed. FG filled with strontium hexaferrite particles have larger Young's modulus value than FG filled with magnetite particles, most likely due to the specific features of the adhesion of the network's polymeric subchains on the surface of the particles. FG networks with xanthan are stronger and have higher modulus than the FG with guar. FG based on magnetite, contract in a magnetic field 0.42 T, whereas some FG based on strontium hexaferrite swell. Weak FG with the lowest concentration of AAm shows a much stronger response to a field, as the concentration of AAm governs the Young's modulus of ferrogel. A small magnetic field magnetoimpedance sensor prototype with Co68.6Fe3.9Mo3.0Si12.0B12.5 rapidly quenched amorphous ribbon based element was designed aiming to develop a sensor working with a disposable stripe sensitive element. The proposed protocol allowed measurements of the concentration dependence of magnetic particles in gels using magnetoimpedance responses in the presence of magnetite and strontium hexaferrite ferrogels with xanthan. We have discussed the importance of magnetic history for the detection process and demonstrated the importance of remnant magnetization in the case of the gels with large magnetic particles.

Effect of cytoskeletal elastic properties on the mechanoelectrical transduction in excitable cells.

This paper addresses the possible mechanism of stretch on cell electrochemical potential change, based on the physicochemical properties of cytoskeletal network. Synthetic polyelectrolyte gel was used as an experimental model of the cytoskeleton. Gel samples with different density of network cross linking were studied. Triangular axial deformations of samples were applied. Simultaneously, the electrochemical (Donnan) potential of the gel was measured between a micropipette electrode pinned into the swollen gel, and a reference electrode in the outer solution. We found that axial deformation shifts the gel potential toward depolarization. The extent of gel depolarization showed a close negative correlation with the Young modulus of the gel. We suggest that the underlying mechanism is likely to be a universal process of counterion adsorption on charged polymer filaments due to the decrease of distance between polymer filaments owing to gel elongation.

Validity of ejection fraction as a measure of myocardial functional state: impact of asynchrony.

AIMS: The goal of this study was to test whether peculiarities of left ventricular (LV) regional function place limits on the validity of ejection fraction (EF) as a measure of the myocardial functional state. METHODS AND RESULTS: Transthoracic and transoesophageal data from patients with a variety of cardiac conditions were used for analysis of LV regional function. The focus was on the effects of mechanical asynchrony. Ejection fraction was calculated on the basis of LV end-diastolic volume and end-systolic volume obtained by two different ways: (i) end-systolic volume as a whole; and (ii) the sum of all regional end-systolic volumes (which may occur at different times). The relative difference, D-EF, between EFs obtained by (i) and (ii) was taken as the 'merit' of EF. A value of zero is the highest merit. Irrespective of the examination method, we found that D-EF was always higher than zero, and that its value depended on the extent of mechanical asynchrony. CONCLUSIONS: Ejection fraction is not the arithmetic average of regional EFs. An increase of asynchrony increases D-EF, i.e. it reduces the merit of EF as a measure of cardiac function.

Stepwise length changes in single invertebrate thick filaments.

Previous experiments on thick filaments of the anterior byssus retractor muscle of Mytilus and the telson-levator muscle of Limulus polyphemus have shown large, reversible length changes up to 23% and 66% of initial length, respectively, within the physiological tension range. Using nanofabricated cantilevers and newly developed high-resolution detection methods, we investigated the dynamics of isolated Mytilus anterior byssus retractor muscle thick filaments. Single thick filaments were suspended between the tips of two microbeams oriented perpendicular to the filament axis: a deflectable cantilever and a stationary beam. Axial stress was applied by translating the base of the deflectable nanolever away from the stationary beam, which bent the nanolever. Tips of flexible nanolevers and stationary beam were imaged onto a photodiode array to track their positions. Filament shortening and lengthening traces, obtained immediately after the motor had imposed stress on the filament, showed steps and pauses. Step sizes were 2.7 nm and integer multiples thereof. Steps of this same size paradigm have been seen both during contraction of single sarcomeres and during active interaction between single isolated actin and myosin filaments, raising the question whether all of these phenomena might be related.

The regional elastic properties analysis of myocardium based on echocardiographic 3-D reconstruction of the left ventricle.

The present study evaluates the myocardium regional elastic properties on the basis of relative thickness change (DeltaHWT) in the left ventricular (LV) wall during the diastolic filling phase. Two-dimensional (2-D) LV long-axis images were obtained with a Powervision-380 (Toshiba) transesophageal echocardiographic imager. Three-dimensional (3-D) reconstruction of the LV was carried out by rotation of the transducer in calibrated steps. Endocardial and epicardial surfaces were approximated to the shape of heart wall by means of spherical functions. At the beginning of the diastolic filling phase, LV endocardial surface was divided into equal angular segments sized about 4 x 4 mm in a spherical coordinate system. To define the displacement direction of the heart wall surface fragments at every moment (frame) of diastolic filling, a new algorithm was developed. The elastic properties of LV wall regions were represented as regional DeltaHWT maps. A qualitative test of the method was implemented according to data from clinical and instrumental inspections of the patients with ischemic heart disease (IHD). Possible error sources were considered to evaluate the method quantitatively. The method root-mean-square error was about 5.4%, including errors of initial data, approximation and rounding off.