Gel Extrusion Research Articles

Metal Cross-Linked Supramolecular Gel Noodles: Structural Insights and Antibacterial Assessment.

Achieving precise control over gelator alignment and morphology is crucial for crafting tailored materials and supramolecular structures with distinct properties. We successfully aligned the self-assembled micelles formed by a functionalized dipeptide 2NapFF into long 1-D "gel noodles" by cross-linking with divalent metal chlorides. We identify the most effective cross-linker for alignment, enhancing mechanical stability, and imparting functional properties. Our study shows that Group 2 metal ions are particularly suited for creating mechanically robust yet flexible gel noodles because of their ionic and nondirectional bonding with carboxylate groups. In contrast, the covalent nature and high directional bonds of d-block metal ions with carboxylates tend to disrupt the self-assembly of 2NapFF. Furthermore, the 2NapFF-Cu noodles demonstrated selective antibacterial activity, indicating that the potent antibacterial property of the copper(II) ion is preserved within the cross-linked system. By merging insights into molecular alignment, gel extrusion processing, and integrating specific functionalities, we illustrate how the versatility of dipeptide-based gels can be utilized in creating next-generation soft materials.

The Injection of Gels Through an Intact Annulus Maintains Biomechanical Performance without Extrusion Risk.

For autologous-disc-derived chondrocyte transplantation (ADCT) a transglutaminase crosslinked gelatine gel and an albumin hyaluronic acid gel, crosslinked with bis-thio-polyethylene glycol, were injected through a syringe into a degenerated intervertebral disc, where they solidified in situ. This biomechanical in vitro study with lumbar bovine motion segments evaluated disc height changes, motion characteristics in a quasi-static spine loading simulators, and the potential extrusion risk of these biomaterials in a complex dynamic multi-axial loading set-up with 100,000 loading cycles. After the injection and formation of the gel in the center of the nucleus, the disc height increase was about 0.3 mm. During cyclic testing, a gradual decrease in height could be detected due to viscoelastic effects and fluid loss. No gel extrusion could be observed for all specimens during the entire test procedure. A macroscopic inspection after dissections showed an accumulation of the solidified gel in the center of the nucleus. The results demonstrate that the injection of in situ solidifying gels through the intact annulus allows for the stable maintenance of the injected gel at the target location, with high potential for use as a suitable scaffold to anchor therapeutically applied cells for disc regeneration within the treated nucleus pulposus.

Pore-scale modeling of preformed particle gel (PPG) extrusion in porous media

Preformed particle gel (PPG) is a promising profile control agent for enhanced oil recovery in heterogeneous reservoirs. For an improved sweep, the remigration behavior of PPG once blocked by pore throats is of crucial importance. In this paper, the process of a hyper-elastic particle passing through a pore throat is simulated, allowing investigation of the extrusion mechanism of PPG with deformation under a certain hydraulic pressure. The results reveal that PPG is subjected to a varying resistance during the process of entering, penetrating and leaving the throat. The maximal radial resistance occurs when the particle center arrives at the narrowest throat, whereas the maximal axial resistance occurs before that. In the meantime, it is shown that the particle gel bears over 80% body strain during the extrusion process through frictional pore throat. The hydraulic pressure needed for the PPG extrusion through the pore throat depends on the mechanical behaviors (hyper-elasticity of PPG, and friction coefficient of the PPG-throat interface) and geometrical properties (the particle size, and the shape of throat wall) of the PPG-throat system. Based on the simulation results, an empirical model is finally established to predict the required driving pressure. Eventually, the pore-scale model is upscaled and employed to attain effective pressure windows for profile-control in a reservoir scale formation with 10 times permeability heterogeneity.

Design Parameters for Injectable Biopolymeric Hydrogels with Dynamic Covalent Chemistry Crosslinks.

Dynamic covalent chemistry (DCC) crosslinks can form hydrogels with tunable mechanical properties permissive to injectability and self-healing. However, not all hydrogels with transient crosslinks are easily extrudable. For this reason, two additional design parameters must be considered when formulating DCC-crosslinked hydrogels: 1) degree of functionalization (DoF) and 2) polymer molecular weight (MW). To investigate these parameters, hydrogels comprised of two recombinant biopolymers: 1) a hyaluronic acid (HA) modified with benzaldehyde and 2) an elastin-like protein (ELP) modified with hydrazine (ELP-HYD), are formulated. Several hydrogel families are synthesized with distinct HA MW and DoF while keeping the ELP-HYD component constant. The resulting hydrogels have a range of stiffnesses, G' ≈ 10-1000Pa, and extrudability, which is attributed to the combined effects of DCC crosslinks and polymer entanglements. In general, lower MW formulations require lower forces for injectability, regardless of stiffness. Higher DoF formulations exhibit more rapid self-healing. Gel extrusion through a cannula (2 m length, 0.25 mm diameter) demonstrates the potential for minimally invasive delivery for future biomedical applications. In summary, this work highlights additional parameters that influence the injectability and network formation of DCC-crosslinked hydrogels and aims to guide future design of injectable hydrogels.

Mineral bioaccessibility in 3D printed gels based on milk/starch/ĸ-carrageenan for dysphagic people

Dysphagia is a condition that affects the ability to chew and swallow food and beverages, having a major impact on people's health and wellbeing. This work developed gel systems with a customized texture suitable for intake by dysphagic people using 3D printing and milk. Gels were developed using skim powdered milk, cassava starch (native and modified by the Dry Heating Treatment (DHT)), and different concentrations of kappa-carrageenan (ĸC). The gels were evaluated in relation to the starch modification process and concentration of gelling agents, 3D printing performance, and suitability for dysphagic people (following both the standard fork test described by the International Dysphagia Diet Standardization Initiative (IDDSI), and also using a new device coupled to a texture analyzer). Moreover, the best formulations were evaluated for mineral bioaccessibility through simulated gastrointestinal digestion based on INFOGEST 2.0 standardized method. The results showed that ĸC had a dominant effect compared to the DHT-modified starch on gel texture, 3D printing performance, and fork tests. The gels obtained by molding or 3D printing resulted in different behaviors during the fork test, which was associated with the gel extrusion process that breaks down their initial structure. The strategies applied to tailor the texture of the milk did not affect the mineral bioaccessibility, which was kept high (>80%).

Rheological characterization of cell-laden alginate-gelatin hydrogels for 3D biofabrication

Biofabrication of tissue models that closely mimic the tumor microenvironment is necessary for high-throughput anticancer therapeutics. Extrusion-based bioprinting of heterogeneous cell-laden hydrogels has shown promise in advancing rapid artificial tissue development. A major bottleneck limiting the rapid production of physiologically relevant tissue models is the current limitation in effectively printing large populations of cells. However, by significantly increasing hydrogel cell-seeding densities, the time required to produce tissues could be effectively reduced. Here, we explore the effects of increasing cell seeding densities on the viscoelastic properties, printability, and cell viability of two different alginate-gelatin hydrogel compositions. Rheological analysis of hydrogels of varying cell seeding densities reveals an inverse relationship between cell concentration and zero-shear viscosity. We also observe that as cell seeding densities increases, the storage moduli decrease, thus lowering the required printing pressures for gel extrusion. We also observe that increasing cell concentration can negatively impact the structural properties of the extruded material by increasing post-print line spreading. We find that hydrogels composed of higher molecular weight alginates and the highest cell-seeding densities (107 cells/mL) yield higher cell viability (>80%) and structural uniformity after printing. The optimized printing parameters determined for the alginate-gelatin bioinks explored may aid in the future rapid fabrication of functional tissue models for therapeutic screening.

Cellulose blends from gel extrusion and compounding with polylactic acid

AbstractCellulose, dissolved in ionic liquids (IL), can be used successfully in the processing of thermoplastics. To recover the ionic liquid while maintaining the thermoplastic properties, other spacers than IL might be introduced into the cellulose network. Such blend materials have been prepared before by solution blending as reported in the literature. In this study, the preparation and investigation of cellulose and polylactic acid (PLA) blends using an extrusion process with an ionic liquid and co‐solvent for intermediate compatibilization is reported. The obtained transparent films show a homogeneous morphology without phase separation. Thermal analysis showed no separated glass transition for PLA, and FTIR showed hydrogen bonding between cellulose and PLA chains. Thermal stability of the blends with a degradation onset around 270°C lies between regenerated cellulose and pure PLA. The blend tensile strength and elongation of ~40 MPa and 1.3%, respectively, were comparable to a multiphase composite containing twice the molecular weight of PLA. Generally, mechanical performance of the blends was strongly influenced by degradation reactions mainly caused by the ionic liquid used, as well as blend morphology. The study shows that transfer from solution to extrusion processing is generally possible to obtain novel cellulose blends.

Fine-Tuning of Molecular Structures to Generate Carbohydrate Based Super Gelators and Their Applications for Drug Delivery and Dye Absorption.

Carbohydrate-based low molecular weight gelators (LMWGs) exhibit many desirable properties making them useful in various fields including applications as drug delivery carriers. In order to further understand the structural connection to gelation properties, especially the influence of halide substitutions, we have designed and synthesized a series of para-chlorobenzylidene acetal protected D-glucosamine amide derivatives. Fifteen different amides were synthesized, and their self-assembling properties were assessed in multiple organic solvents, as well as mixtures of organic solvents with water. All derivatives were found to be gelators for at least one solvent and majority formed gels in multiple solvents at concentrations lower than 2 wt%. A few derivatives rendered remarkably stable gels in aqueous solutions at concentrations below 0.1 wt%. The benzamide 13 formed gels in water and in EtOH/H2O (v/v 1:2) at 0.36 mg/mL. The gels were characterized using optical microscopy and atomic force microscopy, and the self-assembly mechanism was probed using variable temperature 1H-NMR spectroscopy. Gel extrusion studies using H2O/DMSO gels successfully printed lines of gels on glass slides, which retained viscoelasticity based on rheology. Gels formed by the benzamide 13 were used for encapsulation and the controlled release of chloramphenicol and naproxen, as well as for dye removal for toluidine blue aqueous solutions.

Design and implementation of a low cost bio-printer modification, allowing for switching between plastic and gel extrusion

Due to the high cost of bioprinters they are not feasible for proof of concept experiments or educational purposes. Furthermore, the more affordable DIY methods all disable the plastic printing capability of the original printer. Here we present an affordable bio-printing modification that is easy to install and maintains the original capabilities of the printer. The modification used mostly 3D printed parts and is based on the popular, open-source Prusa i3 3D printer. The modifications are kept as simple as possible and uses standard slicing software, allowing for installation by less experienced builders. By using disposable syringes and easily sterilizable parts, an aseptic bioprinting setup can be achieved, depending on the environment. It also allows for 2 component printing as well as UV curing. The bio-printing and curing capabilities were shown by printing and curing an artificial biofilm of an electro-active bacteria, Geobacter sulfurreducens, onto a carbon-cloth electrode which was used in a microbial fuel cell.

Two-Dimensional Gel Electrophoresis: Vertical Isoelectric Focusing.

Two-dimensional gel electrophoresis is one of the most powerful tools for separating proteins based on their size and charge. Two-dimensional gel electrophoresis (2-DE) is very useful to separate two proteins with identical molecular weights but different charges, which cannot be achieved with just sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). Here, a simpler and easier version of 2-DE is presented which is also faster than all the currently available techniques. In this modified version of 2-DE, isoelectric focusing is carried out in the first dimension using a vertical sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) apparatus. Following the first-dimensional IEF, each individual lane is excised from the IEF gel and after a 90° rotation, is inserted into a second-dimensional SDS-PAGE, which can be stained with Coomassie Brilliant Blue for protein analysis or immunoblotted for further analysis. This version of IEF can be run in less than 2h compared to the overnight run required by O'Farrell's method. Difficult tube gel casting and gel extrusion as well as tube gel distortion are eliminated in our method. This method is simpler, faster, and inexpensive. Both dimensions can be done on the same SDS-PAGE apparatus, and up to ten samples can be run simultaneously using one gel.

Preformed particle gel propagation and dehydration through semi-transparent fractures and their effect on water flow

Polymer gels have been widely applied to plug high permeability streaks or fractures, and to improve sweep efficiency of chase waterfloods. This work constructed semi-transparent fracture models to investigate gel propagation and dehydration behaviors using preformed particle gel (PPG) in open fractures. Roubidoux sandstone slabs were used in the models because they could better model the roughness of fractures and PPG dehydration in a real fracture system, which was rarely reported in earlier studies. Injection rate, fracture width, particle size, brine and gel concentration were taken into account to understand their effects on particle gel extrusion. Experimental results showed PPG propagated like a piston along a fracture when the fracture width was smaller than or similar to the particle size; and gravity will dominate the PPG movement when the fracture width was larger than the particle size. PPG dehydration decreased with the increasing gel injection rate, fracture width, and brine concentration used to prepare PPG. Higher PPG injection rates and lower injection rates for chase waterfloods are recommended to improve the sweep efficiency in the matrix. This study could provide an insight into the particular PPG gel treatment for conformance improvement.

Describing flow behavior of polymer gel in fracture using rheology

In many successful conformance controls to reduce excessive water production, large volumes of gels were extruded through fractures during placement. The pressure gradient for gel extrusion depends strongly on fracture width and gel composition. Extrusion experiments directly measure gel properties in fractures, but they are both expensive and time-consuming. The rheology behavior of the gels showed a strong parallel to the results obtained from previous gel extrusion experiments. The previous researches showed two discrepancies and one similarity between the rheology estimation and extrusion experiment. The two discrepancies are: the pressure gradient required to extrude a gel through a fracture substantially greater than anticipated based on rheology measurements; different relationships of pressure gradient versus fracture width. The similarity is the relationships between pressure gradient versus flow rate and shear stress versus shear rate are fairly close. This paper examined these discrepancies and the similarity, in hopes of understand and ultimately substituting the rheology measurements for extrusion experiments.Extensive experiments established that wall slip and first normal stress difference were not responsible for the pressure gradient discrepancy. Steady shear and oscillatory shear data were collected with a rheometer using both smooth and rough parallel-plate geometries and employing various gap heights. Wall-slip effects were present with smooth plates but negligible with rough plates. To explain the discrepancy, we noted that the aperture for gel flow (for mobile gel wormholing through concentrated immobile gel within the fracture) was much narrower than the width of the fracture.Considering the shear-thinning properties of the gels, two models were developed combining power-law model and shell momentum balances. The first model explained the discrepancy of the relationships between pressure gradient versus fracture width. The second model correlated pressure gradient, shear stress, flow rate, and shear rate to bridge the gap between gel rheology in fractures versus in a rheometer and explained the similarity between the rheology measurement and extrusion experiment.

Gelation of a Water-Shutoff Gel at High Pressure and High Temperature: Rheological Investigation

Summary Polymeric gels are used to reduce or shut off excess water in petroleum reservoirs. The strength of polymeric gels needs to be high enough to withstand the water flow. This study investigates the strength of an organically crosslinked polyacrylamide (PAM) with polyethylenimine (PEI) as crosslinker. Dynamic testing measurements at high temperatures up to 130°C (266°F) and high pressure (500 psi) were used. During the gelation process, the rate of crosslinking increases with increased temperature. However, after the crosslinking reactions were completed, G′ was lower at higher temperatures than at lower temperatures. Polymer concentration has a stronger impact on G′ in comparison with the crosslinker. Salinity of mixing water has a negative impact on G′. High G′ was observed in distilled water (1044 Pa) in comparison with field water (725 Pa) at 130°C (266°F). Moreover, samples prepared at alkaline and acidic conditions produced stronger gels compared with samples prepared at neutral conditions. However, the gelation time is longer at a pH of 7. Ammonium chloride is found to be a very effective retarder in comparison with NaCl. The yield stress of the gel was correlated to the pressure gradient for the gel extrusion through fractures. It was found that gels with 7:0.3 and 5:0.3 wt% PAM/PEI gave pressure gradients of 155.5 kPa/m (55.2 psi/m) and 3572 kPa/m (518 psi/m), respectively. The decrease or increase in gel strength was explained through the impact of the different parameters on PAM hydrolysis.

Pore-Level Examination of Gel Destruction During Oil Flow

Summary Pore-scale X-ray computed microtomography (XMT) images were obtained at a variety of oil (hexadecane) throughput values after gel placement in cores [involving a pore-filling Cr(III)-acetate-hydrolyzed polyacrylamide (HPAM) gel]. For each pore in our image volume, we followed oil and water saturations as a function of oil throughput. These studies were performed both in water-wet Berea sandstone and in hydrophobic porous polyethylene cores. In hydrophobic porous polyethylene, oil saturations increased and gel was destroyed (presumably dehydrated) quite quickly in the smallest pores. Also, oil saturations increased and gel was destroyed quickly in the largest pores. In contrast, oil saturations rose much more gradually for the most common or intermediate-size pores (around 10-4 mm3). The minimum in oil saturation vs. pore size may result from a balance between gel dehydration by oil film growth vs. gel extrusion. In contrast, in water-wet Berea sandstone, increases in oil saturation occurred evenly over all pore sizes (10-6 to 0.02 mm3) for all oil throughput values. Consistent with imbibition and drainage studies performed before gel placement, oil apparently had equal access to Berea pores of all sizes and, thus, uniformly dehydrated gel in pores of all sizes. Gel extrusion did not appear to be significant in the Berea pores.

A Simpler and Faster Version of Two-Dimensional Gel Electrophoresis Using Vertical, Mini SDS-PAGE Apparatus

We have modified one of the most useful methods of protein separation; namely, two dimensional gel electrophoresis (2-DE). This modified version of 2-DE is not only simpler and easier but also faster than all the currently available methods. In this method, isoelectric focusing is carried out in the first dimension using a vertical sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) apparatus. Following focusing, each individual lane is excised from this gel and after a 90° rotation, is inserted into a vertical specially fabricated SDS-PAGE gel for the second dimension run, which can be stained with Coomassie Brilliant Blue for protein analysis or immunoblotted for further analysis. This modified version of IEF can be run in less than 2 hours compared to the overnight run required by the O’Farrel method. Difficult tube gel casting and gel extrusion as well as tube gel distortion are eliminated in our method. This method is simpler, faster and inexpensive. Both dimensions can be done on the same SDS-PAGE apparatus and up to 10 samples can be run simultaneously using one gel. We have analyzed human sera, animal saliva, eye and liver tissue samples to verify this method.

Designing the Width and Texture of Vanadium Oxide Macroscopic Fibers: Towards Tuning Mechanical Properties and Alcohol-Sensing Performance

Macroscopic vanadium oxide fibers have been fabricated by an extrusion process. By varying the shear rate associated with the gel extrusion process we have been able to tune the diameter and transversal geometry of the fibers at macroscopic length scales. At the mesoscopic length scale, small-angle X-ray scattering (SAXS) analysis provides evidence for the possibility of fine tuning the degree of alignment of the V2O5 ribbons inside the fibers; this alignment is clearly improved upon increasing the shear rate. Nitrogen physisorption measurements (Brunauer–Emmett–Teller (BET)) indicate that the as-synthesized fibers exhibit poor mesoporosity, largely due to the presence of remaining poly(vinyl alcohol) (PVA) entities. Microscopically, from XRD measurements, the fiber structure appears to be semi-crystalline. 51V magic angle spinning NMR (MAS NMR) spectroscopy reveals that the local environment of 51V is typical of the structure of a V2O5·1.8 H2O xerogel. We demonstrate here that the alignment of the nanoribbon subunits can be tuned via the shear rate applied during the extrusion process, which provides a good handle for tuning the mechanical and sensing properties of the as-synthesized fibers.

Correlation of characteristics of gel extrusion module (GEM) tablet formulation and drug dissolution rate

The purpose of the study was to characterize the swelling properties of controlled release tablet formulations with compositional and processing differences. A correlation was also established between the drug dissolution rate from the controlled release gel extrusion module (GEM) tablet and the swelling properties of the core tablet. The GEM tablet consisted of a core tablet of water swellable Carbopol ® polymer, a neutralizing agent, drug, and excipients. The tablet was subsequently coated with a rigid, water impermeable membrane. A number of holes were then drilled by laser through the impermeable membrane. Dynamic mechanical analysis (DMA), Perkin Elmer DMA7, was used to characterize the swelling properties. During the swelling measurements, the measuring probe and sample were completely submerged in the surrounding medium. The results showed that the formulation containing potassium phosphate dibasic as a neutralizing agent had the highest swelling rate. Correspondingly, this formulation had the highest drug dissolution rate over the same time period. The processing difference included wet granulation and dry roller compaction. The compositional differences included different neutralizing agents, binders or Carbopol ® polymers. The results showed a linear relationship ( r 2=0.954) between the swelling rates of the core tablets and the drug dissolution rates of GEM tablets. No correlation was found between the drug dissolution rates and either the maximum extent of tablet swelling or the time needed to reach the maximum extent of swelling. The results demonstrated that DMA could be used to support both formulation and process development to determine the effects of different compositions and manufacturing processes on drug dissolution rates for swelling controlled release devices.

An Alternative View of Filter-Cake Formation in Fractures Inspired by Cr(III)-Acetate-HPAM Gel Extrusion

SummaryA new model was developed to describe water leakoff from formed Cr(III)-acetate-HPAM gels during extrusion through fractures. This model is fundamentally different from the conventional filter-cake model used during hydraulic fracturing. Even so, it accurately predicted leakoff during extrusion of a guar-borate gel. Thus, the new model may be of interest in hydraulic fracturing. Contrary to the conventional one, the new model correctly predicted the occurrence of wormholes and stable pressure gradients during gel extrusion through fractures.

Static headspace gas chromatographic analysis of the residual solvents in gel extrusion module tablet formulations

A rapid static headspace-gas chromatographic (SHS-GC) method was developed and validated for the quantitation of residual solvents in pharmaceutical gel extrusion module (GEM) tablet formulations. A static headspace sampling technique was utilized to overcome the difficulties imposed by direct injection methods. A Rtx-1701 megabore capillary column was selected to achieve optimal resolution among organic volatile chemicals used commonly in the manufacturing of GEM tablets, residual solvents in the active ingredient and excipients, and other formulation matrix artifacts. A 50-mM pH 3.0 sodium phosphate buffer was used as a sample diluent to minimize matrix effects. The instrumental parameters of the SHS-GC method were optimized for sensitivity and precision. Quantitation was performed by external standard analysis. The SHS-GC method was validated according to regulatory requirements and produced acceptable results with respect to specificity, linearity, range, detection and quantitation limits, precision, and accuracy.

Rheology of Gels Used for Conformance Control in Fractures

SummaryThis paper investigates whether gel behavior in rheometers correlates with that examined during extrusion through fractures. Although qualitative similarities were noted, the pressure gradients during gel extrusion through fractures were substantially greater than the values expected from rheological measurements. Also, the pressure gradient for gel extrusion through fractures varied in an unexpected manner with fracture width.