Porous Hydrogels: Present Challenges and Future Opportunities.

In this feature article, we critically review the physical properties of porous hydrogels and their production methods. Our main focus is nondense hydrogels that have physical pores besides the space available between adjacent cross-links in the polymer network. After reviewing theories on the kinetics of swelling, equilibrium swelling, the structure-stiffness relationship, and solute diffusion in dense hydrogels, we propose future directions to develop models for porous hydrogels. The aim is to show how porous hydrogels can be designed and produced for studies leading to the modeling of physical properties. Additionally, different methods that are used for making hydrogels with physically incorporated pores are briefly reviewed while discussing the potentials, challenges, and future directions for each method. Among kinetic methods, we discuss bubble generation approaches including reactions, gas injection, phase separation, electrospinning, and freeze-drying. Templating approaches discussed are solid-phase, self-assembled amphiphiles, emulsion, and foam methods.

Porous hollow fibers with controllable structures templated from high internal phase emulsions.

A technique to fabricate hollow fibers with porous walls via templating from high internal phase emulsions (HIPEs) has been demonstrated. This technique provides an environmentally friendly process alternative to conventional methods for hollow-fiber productions that typically use organic solvents. HIPEs containing acrylate monomers were extruded into an aqueous curing bath. Osmotic pressure effects, manipulated through differences in salt concentration between the curing bath and the aqueous phase within the HIPE were used to control the hollow structures of polyHIPE fibers. The technique was used to produce porous fibers (with millimeter-scale diameters and micronscale pores) having a hollow core (with a diameter of 50%-75% of the fiber diameter). Two potential applications of the hollow fibers were demonstrated. In vitro drug release studies using these hollow fibers show a controlled release profile that is consistent with the microstructure of the porous fiber wall. In addition, the presence of pores in the walls of polyHIPE fibers also enable size-selective loading and separation of functional materials from an external suspension.

Modeling compressive behavior of open-cell polymerized high internal phase emulsions: effects of density and morphology.

The compressive behavior of poly(HIPE) foams was studied using the developed micromechanics based computational model. The model allowed identifying the morphological parameters governing the foam compressive behavior. These parameters comprise: (i) foam density, (ii) Sauter mean diameter of voids calculated from the morphological analysis of the polydispersed microstructure of poly(HIPE), and (iii) polymer/strut characteristic size identified as the height of the curvilinear triangular cross-section. The model prediction compared closely with the experiments and considered both the linear and plateau regions of the compressive poly(HIPE) behavior. The computational model allows the prediction of structure-property relationships for poly(HIPE) foams with various relative densities and open cell microstructure using the input parameters obtained from the morphology characterization of the poly(HIPE). The simulations provide a pathway for understanding how tuning the manufacturing process can enable the optimal foam morphology for targeted mechanical properties.

Rheological and kinetic study of the ultrasonic degradation of locust bean gum in aqueous saline and salt-free solutions.

The ultrasonic degradation of locust bean gum (LBG) in aqueous solutions has been studied at 25°C for ultrasonication times up to 120 min. Although LBG is not a polyelectrolyte, the degradation extent and kinetics were found to be somewhat sensitive to the ionic conditions in solution, and this is attributed to changes in molecular conformation that can occur in different salt environments. Ultrasonic degradation was tracked by rheological measurements that lead to the determination of intrinsic viscosity for the LBG molecules. A kinetic model was also developed and successfully applied to characterize and predict the degradation results.

Rheological and kinetic study of the ultrasonic degradation of xanthan gum in aqueous solution: effects of pyruvate group.

The influence of the pyruvate group on the efficiency of ultrasonic degradation of xanthan gum in aqueous solution has been studied. Blends of natural and pyruvate-free xanthan gums were ultrasonicated at 20°C for up to 30min and evaluated for molecular-weight degradation by viscometry. Solutions of pure pyruvate-free xanthan exhibited the highest stability to degradation among all blend ratios studied. Removing the pyruvate group is believed to enable the molecular chains to adopt a more compact conformation, which renders the polymer less susceptible to ultrasonication. In addition, the effects of salt on ultrasonic degradation efficiency were studied by using 0.1, 10(-2), or 10(-4)M of NaCl or Na2SO4 in solution prior to ultrasonication. A degradation kinetics model was developed to quantify the degradation behavior. The absence of pyruvate groups renders the xanthan gum less sensitive to the influence of salt, and hence decreases the ultrasonic degradation efficiency.

Rheological and kinetic study of the ultrasonic degradation of xanthan gum in aqueous solutions.

The effectiveness of ultrasound to degrade the molecular weight of xanthan gum in aqueous solutions was investigated for sonication times up to 60 min at 20 °C and for polymer concentrations up to 0.1g/dl. The Huggins equation was found to be applicable to the intrinsic viscosity of xanthan gum prior to sonication, while a truncated form was found to be adequate for estimating the intrinsic viscosity of the degraded xanthan. To better understand the influence of salting-in and salting-out salts (classified on the basis of the Hofmeister series) on degradation, xanthan-gum solutions were pre-mixed with 0.1, 10(-2), 10(-3), or 10(-4)M NaCl or Na2SO4, prior to ultrasonication. A kinetic model was developed and successfully applied to quantify and predict the degradation rates and efficiency. The various reaction rate constants and reaction orders were found to correlate with the different salt species and concentrations used, suggesting that salting-in and salting-out salts could increase or inhibit ultrasonic degradation by adjusting the molecular conformation of the xanthan.

Development of multilayered cell-hydrogel composites using an acoustic focusing technique.

Multilayered composites, composed of mammalian cells arranged in a hydrogel, have been prepared using an acoustic focusing technique. Acoustic focusing is a simple, nonchemical technique that allows for the fast arrangement of cells in matrices where the control of cell geometry is beneficial. Breast cancer cells (MDA-MB231) were dispersed in a 30 wt % solution of poly(ethylene glycol) diacrylate (PEGDA) of molecular weight 400 at a density of 5 x 10(6) cells/mL of PEGDA solution. An ultrasonic field was used to organize the cells before polymerization of PEGDA. Disk-shaped hydrogel composites, typically 1 cm in diameter and 2-mm thick were prepared based on a PEGDA solution volume of 130 microL. At an acoustic frequency of 2.32 MHz, composites having cells positioned within concentric cylindrical shells interspersed with zones of cell-free hydrogel were produced. The cells were located in annuli approximately 80-microm thick and about 300 microm apart. The structure and viability of the cells within these constructs were studied using a fluorescent LIVE/DEAD assay. The viability of the cells was on the order of 50%. For the conditions used in this study, cell death was primarily attributed to exposure of cells to the PEGDA solution prior to polymerization, rather than adverse effects of polymerization or the sound field itself.

Mechanical and cell viability properties of crosslinked low- and high-molecular weight poly(ethylene glycol) diacrylate blends.

There is a strong need for tissue engineering scaffolds that are mechanically robust, exhibit good biocompatibility, and can be made from readily available materials. To this end, blends of commercially available poly(ethylene glycol) diacrylate (PEGDA) with molecular weights of 400 and 3400 were UV-crosslinked at total polymer concentrations that varied systematically from 20 to 40 wt %. The compressive strength and cell viability were determined for each PEGDA mixture. The compressive modulus of the blends was maximized when the weight percent ratio PEGDA3400/400 was about 40/60, with the compressive strength reaching 1.7 MPa. Cell viability results with a LIVE/DEAD fluorescence assay show an average viability of approximately 80% at a total PEGDA concentration of 20 wt % for all blends. Increasing the total polymer concentration increased the compressive modulus of a polymer, but adversely affected cell viability for all the PEGDA blend compositions. The blend composition affected the mechanical behavior of the discs, where a higher degree of crosslinking was achieved by increasing the concentration of shorter chained PEGDA400, whereas elasticity was gained by incorporating longer chained PEGDA3400 into the blends. These results can be exploited for use in tissue engineering applications, where a mechanically robust scaffold is advantageous.

Droplet transport and coalescence kinetics in emulsions subjected to acoustic fields.

A method to aid the separation of the oil phase from aqueous emulsions using a low-intensity, resonant ultrasonic field has recently been developed. The density and compressibility difference between the dispersed and continuous phases within the emulsion results in a net force on the oil drops that pushes them toward the pressure antinodes of the standing-wave field, where coalescence subsequently occurs. A trajectory model is developed to predict the relative motion of drops subjected to the acoustic field. Such trajectories are sensitive to the physical properties and relative size of interacting drops, the initial configuration of the drops, and acoustic field parameters. Model predictions are validated by comparing experimentally observed trajectories with those predicted by the model. The modeling approach is then extended to determine the temporal evolution of the size of the region surrounding a target drop cleared by coalescence as a function of physical and acoustic field parameters. These results form the basis of a population balance model that attempts to track the size-evolution of a drop population coalescing under the influence of an acoustic field.

Fractionation of cell mixtures using acoustic and laminar flow fields.

A fractionation method applicable to different populations of cells in a suspension is reported. The separation was accomplished by subjecting the suspension to a resonant ultrasonic field and a laminar flow field propagating in orthogonal directions within a thin, rectangular chamber. Steady, laminar flow transports the cell suspension along the chamber, while the ultrasonic field causes the suspended cells to migrate to the mid-plane of the chamber at rates related to their size and physical properties. A thin flow splitter positioned near the outlet divides the effluent cell suspension into two product streams, thereby allowing cells that respond faster to the acoustic field to be separated from those cells that respond more slowly. Modeling of the trajectories of individual cells through the chamber shows that by altering the strength of the flow relative to that of the acoustic field, the desired fractionation can be controlled. Proof-of-concept experiments were performed using hybridoma cells and Lactobacillus rhamnosus cells. The two populations of cells could be effectively separated using this technique, resulting in hybridoma/Lactobacillus ratios in the left and right product streams, normalized to the feed ratio, of 6.9 +/- 1.8 and 0.39 +/- 0.01 (vol/vol), respectively. The acoustic method is fast, efficient, and could be operated continuously with a high degree of selectivity and yield and with low power consumption. (c) 2004 Wiley Periodicals, Inc.

Retention and viability characteristics of mammalian cells in an acoustically driven polymer mesh.

A processing approach for the collection and retention of mammalian cells within a high porosity polyester mesh having millimeter-sized pores has been studied. Cell retention occurs via energizing the mesh with a low intensity, resonant acoustic field. The resulting acoustic field induces the interaction of cells with elements of the mesh or with each other and effectively prevents the entrainment of cells in the effluent stream. Experiments involving aqueous suspensions of polystyrene particles were used to provide benchmark data on the performance of the acoustic retention cell. Experiments using mouse hybridoma cells showed that retention densities of over 1.5 x 10(8) cell/mL could be obtained. In addition, the acoustic field was shown to produce a negligible effect on cell viability for short-term exposure.

Single fiber model of particle retention in an acoustically driven porous mesh.

A method for the capture of small particles (tens of microns in diameter) from a continuously flowing suspension has recently been reported. This technique relies on a standing acoustic wave resonating in a rectangular chamber filled with a high-porosity mesh. Particles are retained in this chamber via a complex interaction between the acoustic field and the porous mesh. Although the mesh has a pore size two orders of magnitude larger than the particle diameter, collection efficiencies of 90% have been measured. A mathematical model has been developed to understand the experimentally observed phenomena and to be able to predict filtration performance. By examining a small region (a single fiber) of the porous mesh, the model has duplicated several experimental events such as the focusing of particles near an element of the mesh and the levitation of particles within pores. The single-fiber analysis forms the basis of modeling the overall performance of the particle filtration system.