Effect of particle concentration on the microstructural and macromechanical properties of biocompatible magnetic hydrogels.

We analyze the effect of nanoparticle concentration on the physical properties of magnetic hydrogels consisting of polymer networks of the human fibrin biopolymer with embedded magnetic particles, swollen by a water-based solution. We prepared these magnetic hydrogels by polymerization of mixtures consisting mainly of human plasma and magnetic nanoparticles with OH- functionalization. Microscopic observations revealed that magnetic hydrogels presented some cluster-like knots that were connected by several fibrin threads. By contrast, nonmagnetic hydrogels presented a homogeneous net-like structure with only individual connections between pairs of fibers. The rheological analysis demonstrated that the rigidity modulus, as well as the viscoelastic moduli, increased quadratically with nanoparticle content following a square-like function. Furthermore, we found that time for gel point was shorter in the presence of magnetic nanoparticles. Thus, we can conclude that nanoparticles favor the cross-linking process, serving as nucleation sites for the attachment of the fibrin polymer. Attraction between the positive groups of the fibrinogen, from which the fibrin is polymerized, and the negative OH- groups of the magnetic particle surface qualitatively justifies the positive role of the nanoparticles in the enhancement of the mechanical properties of the magnetic hydrogels. Indeed, we developed a theoretical model that semiquantitatively explains the experimental results by assuming the indirect attraction of the fibrinogen through the attached nanoparticles. Due to this attraction the monomers condense into nuclei of the dense phase and by the end of the polymerization process the nuclei (knots) of the dense phase cross-link the fibrin threads, which enhances their mechanical properties.

Inverse magnetorheological fluids.

We report a new kind of field-responsive fluid consisting of suspensions of diamagnetic (DM) and ferromagnetic (FM) microparticles in ferrofluids. We designate them as inverse magnetorheological (IMR) fluids for analogy with inverse ferrofluids (IFFs). Observations on the particle self-assembly in IMR fluids upon magnetic field application showed that DM and FM microparticles were assembled into alternating chains oriented along the field direction. We explain such assembly on the basis of the dipolar interaction energy between particles. We also present results on the rheological properties of IMR fluids and, for comparison, those of IFFs and bidispersed magnetorheological (MR) fluids. Interestingly, we found that upon magnetic field application, the rheological properties of IMR fluids were enhanced with respect to bidispersed MR fluids with the same FM particle concentration, by an amount greater than the sum of the isolated contribution of DM particles. Furthermore, the field-induced yield stress was moderately increased when up to 30% of the total FM particle content was replaced with DM particles. Beyond this point, the dependence of the yield stress on the DM content was non-monotonic, as expected for FM concentrations decreasing to zero. We explain these synergistic results by two separate phenomena: the formation of exclusion areas for FM particles due to the perturbation of the magnetic field by DM particles and the dipole-dipole interaction between DM and FM particles, which enhances the field-induced structures. Based on the second phenomenon, we present a theoretical model for the yield stress that semi-quantitatively predicts the experimental results.

Dynamic characterization of extremely bidisperse magnetorheological fluids.

In this work, we investigate the stability and redispersibility of magnetorheological fluids (MRFs). These are disperse systems where the solid is constituted by ferro- or ferri-magnetic microparticles. Upon the application of external magnetic field, they experience rapid and reversible increases in yield stress and viscosity. The problem considered here is first of all the determination of their stability against sedimentation, an essential issue in their practical application. Although this problem is typically faced through the addition of thixotropic agents to the liquid medium, in this work, we propose the investigation of the effect of magnetic nanoparticles addition, so that the dispersion medium is in reality a ferrofluid. It is found that a volume fraction of nanoparticles not higher than 3% is enough to provide a long-lasting stabilization to MRFs containing above 30% iron microparticles. In the, in fact unavoidable, event of settling, the important point is the ease of redispersion of the sediment. This is indirectly evaluated in the present investigation by measuring the penetration force in the suspension, using a standard hardness needle. Again, it is found that the nanoparticles addition produces soft sediments by avoiding short-range attractions between the large iron particles. Finally, the performance of the designed MRFs is evaluated by obtaining their steady-state rheograms for different volume fractions of magnetite and different magnetic field strengths. The yield stress is found to be strongly field-dependent, and it can achieve the high values expected in standard magnetorheological fluids but with improved stability and redispersibility.

Rheological characterization of human fibrin and fibrin-agarose oral mucosa substitutes generated by tissue engineering.

In regenerative medicine, the generation of biocompatible substitutes of tissues by in vitro tissue engineering must fulfil certain requirements. In the case of human oral mucosa, the rheological properties of tissues deserve special attention because of their influence in the acoustics and biomechanics of voice production. This work is devoted to the rheological characterization of substitutes of the connective tissue of the human oral mucosa. Two substitutes, composed of fibrin and fibrin-agarose, were prepared in cell culture for periods in the range 1-21 days. The time evolution of the rheological properties of both substitutes was studied by two different experimental procedures: steady-state and oscillatory measurements. The former allows the plastic behaviour of the substitutes to be characterized by estimating their yield stress; the latter is employed to quantify their viscoelastic responses by obtaining the elastic (G') and viscous (G'') moduli. The results demonstrate that both substitutes are characterized by a predominant elastic response, in which G' (order 100 Pa) is roughly one order of magnitude larger than G'' (order 10 Pa). But the most relevant insight is the stability, throughout the 21 days of culture time, of the rheological quantities in the case of fibrin-agarose, whereas the fibrin substitute shows a significant hardening. This result provides evidence that the addition to fibrin of a small amount of agarose allows the rheological stability of the oral mucosa substitute to be maintained. This feature, together with its viscoelastic similitude with native tissues, makes this biomaterial appropriate for potential use as a scaffold in regenerative therapies of human oral mucosa.

Description and performance of a fully automatic device for the study of the sedimentation of magnetic suspensions.

In this paper we describe an experimental setup for the automatic determination of the sedimentation behavior of magnetic suspensions (i.e., disperse systems consisting on ferro- or ferri-magnetic particles in a suitable fluid) of arbitrary volume fraction of solids. The device is based on the evaluation of the inductance of a thin coil surrounding the test tube containing the sample. The inductance L is evaluated from the measurement of the resonant frequency of a parallel LC circuit constructed with the coil and a capacitor of known capacitance. The coil can be moved vertically along the tube at specified steps and time intervals, and from the knowledge of L as a function of the vertical position and time, one can get an image of the particle concentration profiles at given instants of time. The performance of the device is tested against suspensions of spherical iron particles in the micrometer size range dispersed in silicone oil, with various initial concentrations of solids. The sedimentation profiles are then compared with the predictions of existing models for the settling of disperse systems of non-interacting particles.

Study of the magnetorheology of aqueous suspensions of extremely bimodal magnetite particles.

In this paper we describe the magnetorheological behavior of aqueous suspensions consisting of magnetite particles of two size populations, in the micrometer and nanometer scale, respectively. Previous works on the magnetorheology of oil-based fluids demonstrated that the addition of nanoparticles has a very significant effect on the intensity of the magnetorheological effect. The present contribution confirms such results in the case of aqueous fluids, based on the dependence of the yield stress and the viscosity of the bimodal suspensions on both the composition of the mixtures and the magnetic field strength. It is demonstrated that for a given concentration of micrometer particles, increasing the amount of nanometer magnetite provokes a clear enhancement in the yield stress for all the magnetic fields applied. This is proposed to be due to the formation of heterogeneous aggregates that improve the stability of the suspensions and ease the building of well-arranged field-induced structures. The behavior of both the yield stress and the post-yield viscosity agrees better with the predictions of standard chain models when the relative proportion of both types of particles confers optimum stability to the bimodal dispersions.

Study of the magnetorheological response of aqueous magnetite suspensions stabilized by acrylic acid polymers.

In this paper we describe the magnetorheological (MR) behavior of aqueous suspensions consisting of magnetite particles stabilized by poly(acrylic acid) polymers (PAA). A previous work on the colloidal stability of the same systems for different pH values and polymer concentrations demonstrated that the addition of PAA polymers has a very significant effect on the stability. In the present contribution, we study the MR effect of the suspensions stabilized by two different commercial polymers, as a function of pH, magnetic field strength and magnetite volume fraction. All the results are discussed in terms of the interfacial properties of the systems. It is demonstrated that for a given concentration of micrometer particles, the rheological response strongly depends on pH, on the volume fraction of magnetite particles, on the type of polymer added for increasing the stability and on the magnetic field strength. Changing the polymer used provokes clear rheological differences for the same sample conditions (field strength, volume fraction and pH). This is suggested to be due to the hydrophobic/hydrophilic balance of the polymer affecting the magnetic field ability to form magnetic structures by aggregation of the magnetized particles. The results are compared to the predictions of the so-called standard chain model, based on the assumption that the MR effect is the result of the balance between the magnetic interactions (tending to establish some degree of order in the suspension by formation of particle chains in the direction of the field) and hydrodynamic ones (tending to destroy the formed structures by viscous stress on the chains). It is found that the behavior of the yield stress does not agree well with the predictions of the model when the relative proportion of both particle and polymer confers optimum stability to the dispersions. This is likely due to the fact that the presence of the stabilizing polyelectrolyte provokes that the magnetic field is not as effective in structuring the suspension as deduced from the chain model.

Magnetic colloids as drug vehicles.

This review article is a description of the present status of magnetic drug delivery systems (DDS). These are colloidal dispersions of composite nanoparticles consisting of a (polymeric or inorganic) biocompatible matrix and magnetic units, and designed to load and release therapeutic drugs. The matrix, together perhaps with adsorbed polymers or polyelectrolytes, provides the DDS with additional colloidal stability and eventually control of the immune response, and the magnetic inclusions have the goal of providing magnetic guidance. The techniques used in the production of the particles are described. The large surface/volume ratio of the particles brings about a superlative importance of the interface aspects, which are depicted in some detail. Attention is also paid to the possibilities that magnetic DDS offer to be guided by magnetic fields, and to their fate upon entering in contact with the blood proteins and the tumor cells. A description of in vitro and in vivo biodistribution experiments helps in this description. The number of animal experiments performed using magnetic DDS is rather large, but results in humans are far from being sufficient in number, something easily understood. The hopes for improvement and the challenges that must be overcome are described in the closing section.

An experimental method for the measurement of the stability of concentrated magnetic fluids.

In this paper we present a device and method suited to the experimental determination of the sedimentation rate of concentrated suspensions of magnetic particles. The method is based on the measurement of the inductance of one or more sensing coils located at specified positions around a test tube containing the suspension. Such measurement is made possible by the determination of the resonant frequency of a parallel LC circuit in which L is the inductance of the sensing coil and C is the capacity of a capacitor chosen in such a way that the resonant frequency is easily measured. Upon calibration it is possible to relate the resonant frequency to the volume fraction of the particles at the coil location. The method is applied in the present work to the evaluation of the sedimentation kinetics of iron suspensions in base fluids of viscosities ranging from 0.3 to 100 mPa s and volume fractions of solids between 2.5 and 25%. Both if a single coil is used and if a set of three coils at different positions are employed, it is possible to detect the rate of accumulation of particles at the bottom of the container as well as a phenomenon of buoyancy of the largest particles brought about by the hydrostatic push of a dense fluid consisting of the smallest particles in the supporting liquid.

Study of the colloidal stability of concentrated bimodal magnetic fluids.

In this paper, we describe an investigation of the stability and sedimentation behavior of moderately concentrated suspensions of extremely bimodal magnetite particles, including micro- (diameter 1450 nm) and nano- (diameter 8 nm) units. An original method is used, based on the determination of the time dependence of the inductance of a coil surrounding the suspensions. The method proves to be very useful for the determination of the volume fraction of magnetic material in the sensed volume. The observed changes in the resonant frequency of a parallel LC circuit demonstrate that the addition of the magnetite nanoparticles improves the stability and slows down the settling rate of the mixed suspensions. It is proposed that the observed behavior is the result of competition between two processes. One is the formation of a cloud of nanoparticles around the large magnetite units, by virtue of which the latter are maintained at distances beyond the range of DLVO and magnetic attractive interactions. At long times, these composite units will eventually sediment when some critical size is reached, as the small particles are progressively associated with the large ones. The second mechanism is mainly predominant at short times and is related to the higher viscosity of the dispersion medium (the nanoparticles dispersed in the base fluid) for higher nanoparticle concentrations. The stability of the suspensions is discussed in terms of the competition between the two mechanisms.

Preparation and sedimentation behavior in magnetic fields of magnetite-covered clay particles.

This work is devoted to the preparation of magnetite-covered clay particles in aqueous medium. For this purpose, magnetite nanoparticles were synthesized by a coprecipitation method. These magnetic particles are adhered to sodium montmorillonite (NaMt) particles in aqueous suspensions of both materials, by appropriate control of the electrolyte concentrations. The best condition to produce such heteroaggregation corresponds to acid pH and approximately 1 mol/L ionic strength, when the electrokinetic potentials (zeta-potential) of both NaMt and Fe3O4 particles have high enough and opposite sign, as demonstrated from electrophoresis measurements. When a layer of magnetite re-covers the clay particles, the application of an external magnetic field induces a magnetic moment in clay-magnetite particles parallel to the external magnetic flux density. The sedimentation behavior of such magnetic particles is studied in the absence or presence of an external magnetic field in a vertical direction. The whole sedimentation behavior is also strongly affected by the formation of big flocculi in the suspensions under the action of internal colloidal interactions. van der Waals and dipole-dipole magnetic attractions between magnetite-covered clay particles dominate the flocculation processes. The different relative orientation of the clay-magnetite particles (edge-to-edge, face-to-edge, and face-to-face) are discussed in order to predict the most favored flocculi configuration.

Stability and magnetic characterization of oleate-covered magnetite ferrofluids in different nonpolar carriers.

This work describes the preparation and stability evaluation of suspensions consisting of hydrophobic magnetite nanoparticles dispersed in different organic solvents. The ferrite particles are covered by a shell of chemisorbed oleate ions following a procedure that is described in detail. The oleate-covered particles were dispersed in different organic solvents with dielectric constants, epsilon(r), ranging between 1.8 and 9, and the centrifugal field strength needed to remove particle aggregates formed during the synthesis was determined for the different liquid carriers used. A thermodynamic analysis demonstrated that the observed stability of the suspensions in liquids with epsilon(r) < 5 is well correlated with the very low lyophobic attraction between the particles. This can easily be surmounted by thermal agitation, since the van der Waals attraction is negligible. In contrast, for liquids with epsilon(r) > 9, the suspensions become unstable because of the combined action of the van der Waals and lyophobic attractions, the latter being dominant for very polar solvents. Finally, a complete magnetic characterization of the oleate-magnetite powder, as well as of several stable ferrofluids prepared with it, was carried out. From this characterization, the magnetic diameters and magnetic moments of the particles immersed in the different liquid carriers were estimated and compared to those corresponding to the dry magnetic particles. This made it possible to estimate the thickness of the nonmagnetic layer on the particles.

Optical properties of dilute hematite/silicone oil suspensions under low electric fields.

Electrorheology (ER) is the name given to a set of phenomena related to the significant changes experienced by the rheological properties of certain fluids and suspensions upon application of external electric fields. It is mostly explained in terms of the formation of particle aggregates as a consequence of field-induced particle-particle interactions. In this work, we explore such structures by investigating the changes in optical absorbance of hematite/silicone oil suspensions associated to the application of an electric field. We have studied the effect of particle concentration, phi, electric field strength, E(0), and viscosity, eta(m), of the liquid medium on the absorbance-time behavior of the suspensions. Photographs of the electrified suspensions helped in elucidating the structures formed. At low phi values, the absorbance A of electrified suspensions dramatically decreases with time until a constant plateau is reached. The absorbance fall is faster the higher the field, although at long times curves corresponding to different fields tend to merge. In these dilute suspensions particles are observed to migrate toward the electrodes thus clarifying the medium and reducing A. When the concentration of particles is increased, fibrils stretching between the electrodes can be observed in addition to particle deposition on them, as long as the field is kept low. At high fields, migration of the particles to the electrodes occurs whatever the volume fraction. Two mechanisms producing particle-particle interactions are suggested by these data: the conductivity mismatch between the particles and the medium brings about an interfacial or Maxwell-Wagner polarization of the particles; in addition, solids can acquire a net charge provoked by injection from the electrodes. The first mechanism will produce attractive dipole-dipole interactions and hence columns or fibrils. The second one should lead to electrophoretic migration. Structural observations suggest that the latter predominates at high fields. If the viscosity of the fluid phase is increased, the critical electric field values separating both regimes also increase: the electrophoretic motion is hindered and the particle-particle aggregation is enhanced.

Stabilization of magnetorheological suspensions by polyacrylic acid polymers.

This work is devoted to the synthesis and stabilization of magnetorheological suspensions constituted by monodisperse micrometer-sized magnetite spheres in aqueous media. The electrical double-layer characteristics of the solid/liquid interface were studied in the absence and presence of adsorbed layers of high molecular weight polyacrylic acids (PAA; Carbopol). Since the Carbopol-covered particles can be thought of as "soft" colloids, Ohshima's theory was used to gain information of the surface potential and the charge density of the polymer layer. The effect of the pH of the solution on the double-layer characteristics is related to the different conformations of the adsorbed molecules provoked by the dissociation of the acrylic groups present in polymer molecules. The stability of the suspensions was experimentally studied for different pH and polymer concentrations, and in the absence or presence of a weak magnetic field applied. The stability of the suspensions was explained using the classical DLVO theory of colloidal stability extended to account for hydration, steric, and magnetic interactions between particles. Diagrams of potential energy vs interparticle distance show the predominant effect of steric, hydrophilic/hydrophobic, and magnetic interactions on the whole stability of the system. The best conditions to obtain stable suspensions were found when strong steric and hydrophilic repulsions hinder the coagulation between polymer-covered particles, simultaneously avoiding sedimentation by the thickening effect of the polymer solution. When a not too high molecular weight PAA was employed in a low concentration, the task of a long-time antisettling effect compatible with the desired magnetic response of the fluid was achieved.

A slender-body micromechanical model for viscoelasticity of magnetic colloids: comparison with preliminary experimental data.

The storage modulus, G', together with the yield stress, is an essential quantity characterizing the rheological properties of magnetic field-responsive suspensions (magnetorheological fluids or MRF). In this work, we present both experimental and theoretical results on the viscoelastic properties of MRFs. Two MRFs are used: In one the solid phase consists of cobalt ferrite particles + silica gel, with silicone oil as liquid phase. The second system is formed by carbonyl iron + silica gel also dispersed in silicone oil. The cobalt ferrite particles are synthesized as monodisperse colloidal spheres with an average diameter of 850 nm. We describe a new model based on the slender-body approach for hydrodynamic interactions. The predictions of the model are compared to preliminary experimental G' data obtained in a controlled stress plate-plate rheometer. It is found that the model gives the correct order of magnitude for the highest fields in iron suspensions, but underestimates the experimental results obtained in ferrite ones. In the case of high permeability materials such as carbonyl iron, by the inclusion of high-order multipolar interactions and saturation effects we also predict the order of magnitude of the experimental results. When dealing with low permeability cobalt ferrite based MRFs, other effects, such as remanence (at low fields) and saturation (at high fields), must be considered.

Electrophoretic properties of acrylic latex suspensions (Kollicoat MAE 30 D) and ibuprofen.

We have compared the electrophoretic properties (measured on the electrical surface) of the commercial latex Kollicoat MAE 30 D and the non-steroidal anti-inflammatory drug (NSAID) ibuprofen in preparation for attempts to develop a suitable vehicle for the NSAID to obtain a modified release formulation. Electrophoretic mobility of the latex and the active principle was measured in solutions containing different concentrations of inorganic electrolytes (NaCl, CaCl2 and AlCl3) at different pH values. This was considered an indispensable first step for further characterization of the substance's electrical properties. Suspensions of both the latex and the drug had negative mobility values throughout the range of pH values studied here. Of the electrolytes, neither NaCl nor CaCl2 led to positive mobility, and no isoelectric point could be determined. However, AlCl3 at a concentration of 10(-3) M led to the greatest reduction in mobility. We therefore found that trivalent cations were more effective than divalent cations, which in turn were more effective than monovalent cations, in reducing mobility.

Interfacial and rheological properties of humic acid/hematite suspensions.

This work deals with the effect of humic acid (HA) adsorption on the interfacial properties, the stability, and the rheology of aqueous iron oxide (hematite) suspensions. It is first of all demonstrated that HA effectively adsorbs onto hematite, mainly at acid pH. Since the charge of the HA chains is negative, it will be electrostatically attracted to the hematite surface below the point of zero charge of the particles, when they are positively charged. Electrophoresis measurements of hematite suspensions as a function of pH in the presence and absence of HA clearly demonstrate the adsorption of negatively charged entities on the oxide. Since the HA-covered particles can be thought of as "soft" colloids, Ohshima's theory was used to gain information on the surface potential and the charge density of the HA layer (H. Ohshima, in: A.V. Delgado (Ed.), Interfacial Electrokinetics and Electrophoresis, Dekker, New York, 2002, p. 123). A different procedure was also used to ascertain the degree of modification experienced by the hematite surface when placed in contact with HA solutions. The contact angles of selected liquids on pretreated hematite layers lead to the conclusion that the humic acid molecules impart to the particles a significant electron-donor character, in turn increasing their hydrophilicity. All this amount of information is used in the work for the interpretation of the rheological properties of hematite suspensions; the results are consistent with a stabilizing effect of HA adsorption on the suspensions, mainly as a consequence of the increased electrostatic repulsion between particles.

Scaling Behavior of the Rheological Properties of Montmorillonite Suspensions: Correlation between Interparticle Interaction and Degree of Flocculation.

In this work we investigate some aspects of the rheological behavior of sodium montmorillonite (NaMt) suspensions in the pH range 3 to 9, of NaCl concentrations between 10(-3) and 10(-1) M, and of solid concentrations between 5 and 11% w/v. Three kinds of experiments were performed: steady-state viscometry, oscillatory test, and creep recovery. The physical quantities of interest were the yield stress sigma(y) of the suspensions, the elastic rigidity modulus G', and the instantaneous elastic compliance. Furthermore, G' was obtained from oscillatory tests in three different experiments: determination of the viscoelastic linear region, oscillograms, and the gelation process. All quantities were found to scale with the concentration of solids, C, according to a power law of the form Y=k(y)C(n). The exponents n were found to change from approximately 3 to approximately 6 when the pH was increased from 3 to 9 (at constant ionic strength 10(-2) M), although values as high as 10 were estimated when the NaCl concentration was reduced to 1 mM. Such values of n correlate well with the characteristics of the edge-to-face (E-F), edge-to-edge (E-E), and face-to-face (F-F) interparticle interactions. The minimum values of n correspond to maximum E-F attractions, whereas the largest n are associated with strong F-F repulsions. Copyright 2001 Academic Press.