Natural electroactive hydrogel from soy protein isolation

A natural electroactive protein hydrogel was prepared from soy protein isolate (SPI) solution by cross-linking with epichlorohydrin. Under electrical stimulus, such SPI hydrogel quickly bends toward one electrode, showing a good electroactivity. Because of its amphoteric nature, the SPI hydrogel bends either toward the anode (pH < 6) or cathode (pH > 6), depending on the pH of the electrolyte solution. Other factors, such as electric field strength, ionic strength and gel thickness also influence the electromechanical behavior of the SPI hydrogels. Moreover, this SPI hydrogel exhibits a good electroactive behavior under strong acidic (pH = 2 - 3) or basic (pH = 11 - 12) solutions, which is a significant improvement over two other kinds of natural electroactive hydrogels, i.e., chitosan/carboxymethylcellulose and chitosan/carboxymethylchitosan hydrogel, which we reported previously. The wide pH range and good electroactivity of this natural protein hydrogel suggests its great potential for microsensor and actuator applications, especially in the biomedical field, and also to increase the scope of natural polymer-based electroactive hydrogels.     

Electrical behavior of polymer hydrogel composed of poly(vinyl alcohol)-hyaluronic acid in solution

Interpenetrating polymer networks (IPN), as polymer hydrogels composed of poly(vinyl alcohol) (PVA) and hyaluronic acid (HA), which exhibited electrical sensitive behavior were prepared. The swelling behavior of the IPN/HA IPN was studied by immersing the gel in various concentrations of aqueous NaCl solutions and various pH buffer solutions. The response of the PVA/HA IPN to electric fields stimuli was also investigated. When swollen IPN was placed between a pair of electrodes, and an electric field applied, it exhibited bending behavior. The PVA/HA IPN also displayed stepwise bending behavior, depending on the magnitude of the electric stimulus. Also, for use in biosensors application, their bending behavior was studied in Hank's solution at pH 7.4.     

Poly (l-lysine) based semi-interpenetrating polymer network as pH-responsive hydrogel for controlled release of a model protein drug streptokinase

With the aim of developing a pH-sensitive controlled drug release system, a poly (L-lysine) (PLL) based cationic semi-interpenetrating polymer network (semi-IPN) has been synthesized. This cationic hydrogel was designed to swell at lower pH and de-swell at higher pH and therefore be applicable for achieving regulated drug release at a specific pH range. In addition to the pH sensitivity, this hydrogel was anticipated to interact with an ionic drug, providing another means to regulate the release rate of ionic drugs. This semi-IPN hydrogel was prepared using a free-radical polymerization method and by crosslinking of the polyethylene glycol (PEG)-methacrylate polymer through the PLL network. The two polymers were penetrated with each other via interpolymer complexation to yield the semi-IPN structures. The PLL hydrogel thus prepared showed dynamic swelling/de-swelling behavior in response to pH change, and such a behavior was influenced by both the concentrations of PLL and PEG-methacrylate. Drug release from this semi-IPN hydrogel was also investigated using a model protein drug, streptokinase. Streptokinase release was found to be dependent on its ionic interaction with the PLL backbones as well as on the swelling of the semi-IPN hydrogel. These results suggest that a PLL semi-IPN hydrogel could potentially be used as a drug delivery platform to modulate drug release by pH-sensitivity and ionic interaction.     

A new amphoteric superabsorbent hydrogel based on sodium starch sulfate

A new amphoteric superabsorbent hydrogels were synthesized by graft copolymerization blending based on acrylamide (AM), diallydimethylammonium chloride (DMDAAC) and sodium starch sulfate (SSS). The effect of polymerization conditions on swelling capacity was investigated. The results showed that the swelling capacity was affected by various factors, such as polymerization temperature, concentration of initiator and crosslinker, and dose of AM. Additionally, the results testified that salt bond was a potential crosslinking factor in the amphoteric hydrogel. The maximum swelling capacity in distilled water and saline solution reached 1493.1 and 91.0 g/g, respectively. These results were compared with those obtained from original starch-based hydrogel.     

Stimuli responsive self-assembled hydrogel of a low molecular weight free dipeptide with potential for tunable drug delivery

Bottom-up fabrication by molecular self-assembly is now widely recognized as a potent method for generating interesting and functional nano- and mesoscale structures. Hydrogels from biocompatible molecules are an interesting class of mesoscale assemblies with potential biomedical applications. The self-assembly of a proteolysis resistant aromatic dipeptide containing a conformational constraining residue (DeltaPhe) into a stable hydrogel has been studied in this work. The reported dipeptide has free -N and -C termini. The hydrogel was self-supportive, was fractaline in nature, and possessed high mechanical strength. It was responsive to environmental conditions like pH, temperature, and ionic strength. The gel matrix could encapsulate and release bioactive molecules in a sustained manner. The described hydrogel showed no observable cytotoxicity to the HeLa and L929 cell lines in culture.     

Model development and numerical simulation of electric-stimulus-responsive hydrogels subject to an externally applied electric field

Based on a multi-phasic mixture theory with consideration of ionic diffusion and convection, a multi-physic model, called the multi-effect-coupling electric-stimulus (MECe) model, is developed for simulation of responsive behavior of the electric-sensitive hydrogels when they are immersed into a bathing solution subject to an externally applied electric field. In the developed model, with chemo-electro-mechanical coupling effects, the convection-diffusion equations for concentration distribution of diffusive ions incorporate the influence of electric potential. The electroneutrality condition is replaced by the Poisson equation for distribution of electric potential. The steady and transient analyses of hydrogel deformation are easily carried out by the continuity and momentum equations of the mixture phase. Further, the computational domain of the present model covers both the hydrogel and the surrounding solution. In order to solve the present mathematical model consisting of multi-field coupled nonlinear partial differential governing equations, a hierarchical iteration technique is proposed and a meshless Hermite-Cloud method (HCM) is employed. The steady-state simulation of the electric-stimulus responsive hydrogel is numerically conducted when it is subjected to an externally applied electric field. The hydrogel deformation and the ionic concentrations as well as electric potentials of both the hydrogel and external solution are investigated. The parameter influences on the swelling behaviors of the hydrogel are also discussed in detail. The simulating results are in good agreement with the experimental data and they validate the presently developed model.     

Modeling and simulation of the swelling behavior of pH-stimulus-responsive hydrogels

The modulation of the swelling ability of the hydrogel matrix by pH-stimulus enables the dynamic control of the swelling forces, thereby obtaining effective diffusivity and permeability of the solutes, or mechanical energy from the hydrogel. In this work, a chemo-electro-mechanical model describing hydrogel behavior, based on multi-field effects, is developed to simulate the swelling and shrinking of these fascinating bio-materials, and it is termed the multi-effect-coupling pH-stimulus (MECpH) model. This model accounts for the ionic fluxes within both the hydrogel and solution, the coupling between the electric field, ionic fluxes, and mechanical deformations of the hydrogel. The main contribution of this model is to incorporate the relationship between the concentrations of the ionized fixed-charge groups and the diffusive hydrogen ion, which follows a Langmuir isotherm, into the Poisson-Nernst-Planck system. To validate this MECpH model, one-dimensional steady-state simulations under varying pH solution are carried out via a meshless Hermite-Cloud methodology, and the numerical results are compared with available experimental data. It is shown that the presently developed MECpH model is accurate, efficient, and numerically stable.     

Nitrocinnamate-functionalized gelatin: synthesis and "smart"hydrogel formation via photo-cross-linking

Gelatin having p-nitrocinnamate pendant groups (Gel-NC) was prepared via an efficient one-pot synthesis, yield >87%. (1)H NMR data indicated that 1 mol of gelatin was modified with 18 +/- 6 mol of the photosensitive group. Upon exposure to low-intensity 365 nm UV light and in the absence of photoinitiators or catalysts, Gel-NC cross-linked within minutes into a gelatin-based hydrogel as monitored by UV-vis spectroscopy. The degree of swelling of this biodegradable hydrogel in aqueous solutions responded to changes in Gel-NC concentration levels, the ionic strength of the aqueous solutions, and photo-cross-linking time. Topography changes associated with phase transition resulting from "photocleavage" of the hydrogel network with 254 nm UV light were studied with AFM. Both Gel-NC and its hydrogel expressed low toxicity to human neonatal fibroblast cells. In addition, gelatin-based microgels were prepared via the photo-cross-linking of Gel-NC within inverse micelles.     

Direct electrochemistry and electrocatalysis of heme-proteins entrapped in agarose hydrogel films

Three heme-proteins, including myoglobin (Mb), hemoglobin (Hb) and horseradish peroxidase (HRP), were immobilized on edge-plane pyrolytic graphite (EPG) electrodes by agarose hydrogel. The proteins entrapped in the agarose film undergo fast direct electron transfer reactions, corresponding to FeIII = e- --> FeII. The formal potential (E degrees'), the apparent coverage (Gamma), the electron transfer coefficient (alpha) and the apparent electron transfer rate constant (ks) were calculated by integrating cyclic voltammograms or performing nonlinear regression analysis of square wave voltammetric (SWV) experimental data. The E degrees's are linearly dependent on solution pH (redox Bohr effect), indicating that the electron transfer was proton-coupled. Ultraviolet visible (UV-Vis) and reflection-absorption infrared (RAIR) spectra suggest that the conformation of proteins in the agarose film are little different from that proteins alone, and the conformation changes reversibly in the range of pH 3.0-10.0. Atomic force microscopy (AFM) images of the agarose film indicate a stable and crystal-like structure formed possibly due to the synergistic interaction of hydrogen bonding between N,N-dimethylformamide (DMF), agarose hydrogel and heme-proteins. This suggests a strong interaction between the heme-proteins and the agarose hydrogel. DMF plays an important role in immobilizing proteins and enhancing electron transfer between proteins and electrodes. The mechanisms for catalytic reduction of hydrogen peroxide and nitric oxide (NO) by proteins entrapped in agarose hydrogel were also explored.     

Swelling behavior of hyaluronic acid/polyallylamine hydrochloride multilayer films

The reversible swelling behavior of multilayer films containing hyaluronic acid and polyallylamine hydrochloride was investigated using in situ ellipsometry, since many of the natural functions and applied uses of hyaluronic acid are related to the extraordinary ability of this biopolymer to swell, and to respond conformationally to the local solution environment. This swelling was observed to be substantial, and depended strongly on the film thickness, the pH conditions used to prepare the films, and the swelling solution pH and ionic strength. The swelling results were also rationalized in terms of the dissociation behavior of the polyelectrolytes in the multilayer assemblies, measured by the zeta potential, on colloidal particles. The films were found to swell by as much as 8 times their dry thickness, and the extent of film hydration was observed to depend on the thickness of the films in a nonlinear fashion. This was related to the internal structure of the films, which is dictated by the assembly pH conditions. In addition, the swelling solution pH and ionic strength influence the electrostatic environment in the films and, in turn, have a substantial effect on the overall swelling behavior.     

Preparation and characterization of a novel pH-sensitive chitosan-g-poly (acrylic acid)/attapulgite/sodium alginate composite hydrogel bead for controlled release of diclofenac sodium

A series of pH-sensitive composite hydrogel beads composed of chitosan-g-poly (acrylic acid)/attapulgite/sodium alginate (CTS-g-PAA/APT/SA) was prepared as drug delivery matrices crosslinked by Ca²⁺ owing to the ionic gelation of SA. The structure and surface morphology of the composite hydrogel beads were characterized by FTIR and SEM, respectively. pH-sensitivity of these composite hydrogels beads and the release behaviors of drug from them were investigated. The results showed that the composite hydrogel beads had good pH-sensitivity. The cumulative release ratios of diclofenac sodium (DS) from the composite hydrogel beads were 3.76% in pH 2.1 solution and 100% in pH 6.8 solutions within 24 h, respectively. However, the cumulative release ratio of DS in pH 7.4 solution reached 100% within 2 h. The DS cumulative release ratio reduced with increasing APT content from 0 to 50 wt%. The drug release was swelling-controlled at pH 6.8.     

Modeling and simulation of deformation of hydrogels responding to electric stimulus

A model for simulation of pH-sensitive hydrogels is refined in this paper to extend its application to electric-sensitive hydrogels, termed the refined multi-effect-coupling electric-stimulus (rMECe) model. By reformulation of the fixed-charge density and consideration of finite deformation, the rMECe model is able to predict the responsive deformations of the hydrogels when they are immersed in a bath solution subject to externally applied electric field. The rMECe model consists of nonlinear partial differential governing equations with chemo-electro-mechanical coupling effects and the fixed-charge density with electric-field effect. By comparison between simulation and experiment extracted from literature, the model is verified to be accurate and stable. The rMECe model performs quantitatively for deformation analysis of the electric-sensitive hydrogels. The influences of several physical parameters, including the externally applied electric voltage, initial fixed-charge density, hydrogel strip thickness, ionic strength and valence of surrounding solution, are discussed in detail on the displacement and average curvature of the hydrogels.     

Chemically cross-linked chitosan hydrogel loaded with gelatin for chondrocyte encapsulation

Composite hydrogels can be used as a scaffolding material for chondrogenesis, which requires a biomimetic environment to maintain chondrocyte morphology and phenotype. In this study, gelatin molecules were loaded into a hydrogel polymerized from a chitosan derivative (CML) to form a semi-interpenetrating polymer network. While the porous structure of the hydrogels in the dry state was not dependent on the gelatin content, the collapse extent and pore size decreased as the gelatin content increased. The gelatin loading also reduced the swelling ratio of the CML hydrogel and enhanced the hydrogel strength at 20°C due to gelation of the gelatin. The release behavior of the gelatin from the CML hydrogel could be controlled by many factors, such as the amount of gelatin, temperature, and solution pH. The weight loss of the composite hydrogel was expedited after gelatin loading and showed a positive relationship with the gelatin content. The results of in vitro cell culture in the hydrogels revealed that gelatin loading improved cell viability and promoted proliferation and glycosaminoglycans secretion of chondrocytes. This new scaffold production technology for chondrocyte encapsulation provides a further step towards CML applications in tissue engineering and other biomedical areas.     

Novel biodegradable polyphosphate cross-linker for making biocompatible hydrogel

To obtain a novel biodegradable cross-linker, polymerizable polyphosphate (PIOP) was synthesized by ring-opening polymerization of 2-i-propyl-2-oxo-1,3,2-dioxaphospholane with 2-(2-oxo-1,3,2-dioxaphosphoroyloxyethyl methacrylate) (OPEMA). The number averaged molecular weight of the PIOP was 1.2 x 10(4), and the number of OPEMA units in one PIOP molecule was 2.2. Nonenzymatic degradation of the PIOP was evaluated in various pH aqueous media. The degree of hydrolysis was dependent on the pH; that is, it increased with an increase in the pH of the medium. At pH 11.0, the PIOP completely degraded in only 6 days. The poly[2-methacryloyloxyethyl phosphorylcholine (MPC)] cross-linked with the PIOP was prepared by radical polymerization. This polymer could form hydrogel, and the free water fraction in the hydrogel was high. The enzymatic activity of trypsin in contact with the hydrogel was similar to that in buffer solution. There is no adverse effect caused by the hydrogel to reduce the function of the trypsin. The cytotoxicity of poly(MPC) and degraded PIOP was evaluated using v79 cells, and it was not observed in either case. In conclusion, PIOP is a hydrolyzable polymer, which can be used as a cross-linker, and novel hydrogels having biodegradability and biocompatibility were prepared from poly(MPC) cross-linked with the PIOP.     

Electric field effects on immobilized urease activity.

The behavior of an enzyme/membrane system containing urease is studied when an external electric field is applied. The device using a potential difference across the enzyme/membrane system is first described. Optimal operating conditions with respect to substrate concentration, ionic strength and pH are studied. Possible mechanisms of the change in membrane activity by electric field are discussed.     

Contribution of electrodiffusion to the dynamics of electrically stimulated changes in mechanical properties of collagen membranes

We have studied the kinetics of oscillatory tensile forces in collagen membranes. These forces were generated by sinusoidal electric fields applied across the membrane. Both the magnitude and phase of the measured force changed with frequency over a three-decade range. The membrane-separated electrolyte baths had different ionic strength but identical non-isoelectric pH. Changes in intramembrane ionic strength due to the electric field were calculated over the same frequency range via an electrodiffusion model that was generalized to include convection and electrokinetic coupling. A comparison of the experimental and theoretical phases and amplitudes versus frequency suggests that electrodiffusion is the dominant rate-limiting process in this electromechanochemical transduction. These results are relevant to electrostatic interactions in connective tissues and to membrane-based filtration devices in which membrane permeability may be actively varied and controlled by an applied electric field.     

Transient simulation of kinetics of electric-sensitive hydrogels

Kinetics of the hydrogels responsive to electric stimulus due to an externally applied electric field is modeled for the first time through transient simulation. The mathematical model employed is called the multi-effect-coupling electric-stimulus (MECe) model, which is developed with consideration of multi-phases and multi-physics. Transient simulation by the MECe model is examined with available experimental data and good agreement is achieved. The kinetics of ionic concentration of diffusive species is simulated. The simulation also predicts the influences of several important parameters on the hydrogel deformation, including the externally applied electric voltage, initially fixed charge density and surrounding bath solution concentration.     

A transient simulation to predict the kinetic behavior of hydrogels responsive to electric stimulus

A kinetic analysis of the response of electric-sensitive hydrogels to an externally applied electric field is conducted for the first time through modeling and transient simulation. This model, called the multieffect coupling electric stimulus (MECe), considers the effects of multiphases and multiphysics. Its extended application to transient simulation is validated against available experimental data, and good agreement is achieved. The concentration kinetics of ionic species is simulated. The simulation predicts the kinetic behavior of the hydrogels with consideration of the influences of important parameters such as the electric potential, fixed-charge density, bath solution concentration, and hydrogel average curvature.     

Ultrathin hydrogel films for rapid optical biosensing

Novel biosensors have been designed by reporting an analyte-induced (de)swelling of a stimuli-responsive hydrogel (usually in a form of thin film) with a suitable optical transducer. These simple, inexpensive hydrogel biosensors are highly desirable, however, their practical applications have been hindered, largely because of their slow response. Here we show that quick response hydrogel sensors can be designed from ultrathin hydrogel films. By the adoption of layer-by-layer assembly, a simple but versatile approach, glucose-sensitive hydrogel films with thickness on submicrometer or micrometer scale, which is 2 orders of magnitude thinner than films used in ordinary hydrogel sensors, can be facilely fabricated. The hydrogel films can not only respond to the variation in glucose concentration, but also report the event via the shift of Fabry-Perot fringes using the thin film itself as Fabry-Perot cavity. The response is linear and reversible. More importantly, the response is quite fast, making it possible to be used for continuous glucose monitoring.     

Electrohydrodynamic instabilities and segregation of polysaccharides in capillary polymer solution electrophoresis

During capillary electrophoresis of negatively charged polysaccharides in polymer solutions as sieving media, concentration fluctuations develop due to electrohydrodynamic instabilities caused by polarization of the polyelectrolytic chains. This leads to deviations from electroneutrality far beyond the Debye layer and segregation of the initially homogeneous sample solution into aggregated sample‐rich domains as verified by epifluorescence videomicroscopy imaging. As a result, anomalous and irregular peak profiles are obtained impeding the characterization of such complex sample mixtures. This effect appears at an electric field strength threshold value that depends on the molecular weight of the solute polymer molecules, pH, type and concentration of the polymer solution sieving media, and buffering conditions. The magnitude increases with increasing field strength and amount of sample injected. The aggregation onset, as evaluated by the value of the threshold potential, is affected by the charge density of the sample polymer molecules and Debye screening effects and investigated through variation of pH and ionic strength, respectively. Exchange of a simple base buffer component for small and multiply charged organic bases markedly increases the electric field strength necessary to trigger the electrohydrodynamic instabilities. Ultimately, the threshold value could be increased more than seven times by addition of an oppositely charged aminodextran polymer, thereby decreasing the analysis time. © 1999 John Wiley & Sons, Inc. Biopoly 49: 515–524, 1999