Cross-linked Polyacrylamide Hydrogel Research Articles

Rationally designed β-cyclodextrin-crosslinked polyacrylamide hydrogels for cell spheroid formation and 3D tumor model construction

In vitro tumor models are essential for understanding tumor behavior and evaluating tumor biological properties. Hydrogels that can mimic the tumor extracellular matrix have become popular for creating 3D in vitro tumor models. However, designing biocompatible hydrogels with appropriate chemical and physical properties for constructing tumor models is still a challenge. In this study, we synthesized a series of β-cyclodextrin (β-CD)-crosslinked polyacrylamide hydrogels with different β-CD densities and mechanical properties and evaluated their potential for use in 3D in vitro tumor model construction, including cell capture and spheroid formation. By utilizing a combination of β-CD-methacrylate (CD-MA) and a small amount of N,N′-methylene bisacrylamide (BIS) as hydrogel crosslinkers and optimizing the CD-MA/BIS ratio, the hydrogels performed excellently for tumor cell 3D culture and spheroid formation. Notably, when we co-cultured L929 fibroblasts with HeLa tumor cells on the hydrogel surface, co-cultured spheroids were formed, showing that the hydrogel can mimic the complexity of the tumor extracellular matrix. This comprehensive investigation of the relationship between hydrogel mechanical properties and biocompatibility provides important insights for hydrogel-based in vitro tumor modeling and advances our understanding of the mechanisms underlying tumor growth and progression.

Double networks hybrid hydrogels of silica nanoparticles/polyacrylamide: Network stiffness, viscoelastic, mechanical and adhesion properties

Today, the challenge of enhancing the strength and adhesion of the polyacrylamide hydrogel network is still a major concern in many applications. This study investigates the effect of silica nanoparticle concentration on the cross-linked polyacrylamide hydrogel’s gelation, viscoelastic, structural, and adhesion properties. The hybrid hydrogels were evaluated using DSC, XRD, SEM, and rheological analysis to determine their enthalpy of cross-linking, crystallinity, morphology, and elastic properties. The results of kinetic analysis confirmed the catalytic effect of silica nanoparticles on the gelation kinetics. A deviation from the elastic behavior of the unfilled hydrogel was found from the rheological studies. Using the Weibull Model to describe the creep test results showed a significant increase in retardation time with increasing silica nanoparticles content up to the percolation threshold of 0.24 wt.%. This confirmed the development of a more viscous behavior due to the formation of a physical network of nano-silica particles. Based on the DSC energy of hydrogels, both chemical and physical tie points (approximately 19 covalent crosslinking points) were calculated. The hydrogel containing 9 wt.% of silica nanoparticles demonstrated significant improvement in density, and adhesion to the metal surface by about 100% and 350%, respectively. As a result of this study, the hydrogel containing 9 wt% of silica nanoparticles (H9) is suggested for various field studies, such as oil well plugging industries.

Histologic and cytologic changes in normal equine joints after injection with 2.5% injectable polyacrylamide hydrogel reveal low-level macrophage-driven foreign body response.

The data presented in this paper are derived from an in vivo study performed to characterize the nature of the synovial integration process of a 2.5% synthetic cross-linked injectable polyacrylamide hydrogel (2.5 iPAAG) injected IA in horses. 10 healthy horses not suffering from OA or signs of joint disease were administered 50 or 100 mg 2.5 iPAAG in a total of 13 metacarpophalangeal or middle carpal joints. Injected joints were examined at 0, 14, 42, and/or 90 days postinjection. Parameters investigated included clinical examination, synoviocentesis, gross pathology, histology, and scanning electron microscopy. All horses remained clinically normal, with no adverse events recorded throughout the study period. Gross postmortem did not reveal any significant findings. Arthrocentesis cytology parameters remained within clinically normal levels throughout the study. Synovial histology demonstrated that cellular infiltration of macrophages, villus hyperplasia, and vascularization were significantly higher in 2.5 iPAAG-injected joints compared to controls. Scanning electron microscopy confirmed that the 2.5 iPAAG demonstrated an extensive tissue integration as a 3-D scaffolding structure with intact cross-linked strands. Results confirm that an IA injection of 2.5 iPAAG induces a typical foreign body response that is predominately macrophage driven with no evidence of fibrosis or mineralization. Integration of the gel is evident by 14 days, with no free gel remaining in the joint cavity at this time.

Polymer gel amended sandy soil with enhanced water storage and extended release capabilities for sustainable desert agriculture

Herein, we report a facile preparation of super-hydrophilic sand by coating the sand particles with cross-linked polyacrylamide (PAM) hydrogels for enhanced water absorption and controlled water release aimed at desert agriculture. To prepare the sample, 4wt% of aqueous PAM solution is mixed with organic cross-linkers of hydroquinone (HQ) and hexamethylenetetramine (HMT) in 1:1 weight ratio and aqueous potassium chloride (KCl) solution. A specific amount of the above solution is added to the sand well mixed and subsequently cured at 150 °C for 8 h. The prepared super-hydrophilic sands were characterized by Fourier-transform infrared spectroscopy (FT-IR) for chemical composition and X-ray diffraction (XRD) for successful polymer coating onto the sand. The water storage for the samples was studied by absorption kinetics at various temperature conditions and extended water release was studied by the water desorption kinetics. The water swelling ratio for the super-hydrophilic sand has reached a maximum of 900% (9 times its weight) at 80 °C within 1 h. The desorption kinetics of the samples showed that the water can be stored for up to a maximum of 3 days. Therefore, super-hydrophilic sand particles were successfully prepared by coating with PAM hydrogels with a great potential to be used in sustainable desert agriculture.

The effect of three types of cross-linked hydrogels and volume fraction of polyacrylamide on the swelling and thermal behavior using molecular dynamics simulation

The technology of hydrogels is three-dimensional polymer networks with transverse connections that can adsorb water or biofluids. These compounds can adsorb water without dissolving. Natural hydrogels are considered due to their variety, abundance, cheapness, non-toxicity, and biocompatibility with synthetic hydrogels. In this research, the effect of three types of cross-linked hydrogels polyacrylamide (PAM), polyvinyl alcohol (PVA), and polyethylene glycol (PEG) hydrogels), and volume fraction (5–15%) of PAM on the swelling, and thermal behavior (TB) of simulated samples were studied using molecular dynamics (MD) simulations. The results show that among the simulated hydrogels, the structure of PAM had better atomic behavior and TB. PAM hydrogel had the highest swelling, heat flux (HF), and thermal conductivity (TC), with a numerical value of 342,722 Å3, 1583 W/m2, and 0.57 W/m.K after 10 ns. In the following, by increasing the volume fraction of PAM hydrogel from 5% to 15%, swelling increased to 377,986 Å3, and the TC with 10% of PAM increased from 0.53 (W/m.K) to 0.66 (W/m.K). Furthermore, HF of the sample with 15% of PAM was increased from 1423 (W/m2) to 1761 (W/m2) after 10 (ns). Consequently, by increasing the volume fraction of PAM hydrogel, TB of simulated structure was improved.

Hydrogel Coatings on Container Surfaces Reduce Protein Aggregation Caused by Mechanical Stress and Cavitation.

This work reports the ability of hydrogel coatings to protect therapeutic proteins from cavitation-induced aggregation caused by mechanical stress. Here, we show that polyacrylamide hydrogel coatings on container surfaces suppress mechanical shock-induced cavitation and the associated aggregation of intravenous immunoglobulin (IVIg). First, crosslinked polyacrylamide hydrogels were grown on the surfaces of borosilicate glass vials. Treatment with ultrasound showed that these hydrogel surfaces suppressed cavitation events to levels below those found for unfunctionalized borosilicate glass. Next, IVIg solutions were loaded into these vials and subjected to tumbling, horizontal shaking, and drop testing. Aggregation was quantified by bisANS fluorescence staining and particle counting by flow imaging microscopy (FIM). In all cases, the presence of polyacrylamide hydrogels on the vial surfaces reduced the amount of IVIg aggregation and the number of particulates. In addition, the polyacrylamide appeared to have a protective effect that prevented additional aggregates from forming at extended tumbling times. Finally, drop test studies showed that the polyacrylamide coatings suppressed detectable cavitation. This work reveals how even a simple hydrogel vial coating can have a profound effect on stabilizing protein therapeutics.

Porous manganese dioxide nanosheets on modified graphite felt for cathodes in high-capacity flexible Zinc-MnO2 batteries

Modified graphite felt (MGF) is a flexible substrate with many advantages and a simple one-step method involving HNO3 is designed to activate graphite felt by increasing the amount of oxygen-containing functional groups and mesopores. Owing to the etching effect, excellent hydrophilicity beneficial to loading of α-MnO2 is achieved to facilitate the formation of MnO2/MGF. The MnO2/MGF structure serves as the cathode in a flexible Zn//MnO2 battery which also consists of a cross-linked polyacrylamide hydrogel as the electrolyte and separator and a Zn flake as the anode. The flexible Zn–MnO2 battery has excellent energy storage behaviors and cycling durability such as a high areal capacity of 1.26 mA h cm−2 at 4 mA cm−2 as well as capacity retention of 99.8% over 1000 cycles. Furthermore, the battery provides a remarkable energy density of 1.82 mW h cm−2 at a power density of 3.7 mW cm−2. The modification strategy and materials have large potential in wearable and flexible devices.

Development of bromide-selective Diffusive Gradients in Thin-Films for the measurement of average flow rate of streams

Diffusive Gradients in Thin-Films (DGT) have traditionally been used to measure time-weighted average concentration in water. We tested whether Br−-DGT in combination with the trace-dilution flow rate method, could be used as a new approach for measuring water flow rate. A novel bromide selective DGT based on the Purolite Bromide Plus anion exchange resin (Br−-DGT) was developed, which provided environmental bromide concentrations comparable to grab samples. The Br−-DGT provided quantitative bromide concentrations at a range of pH, competing ion concentrations, and in synthetic natural solution. The uptake efficiency was 95.7 ± 3.4%, and the elution efficiency was 95.5 ± 4.7%. The absorption maximum/saturation point of each binding disk was 0.684 ± 0.001 mg. Bromide adsorption to the binding layer was linear to 44.1% of the total binding capacity, 0.302 mg. The determined diffusion coefficient through the agarose cross-linked polyacrylamide (APA) hydrogels was 1.05 × 10−5 cm2 s−1 at 17.9 °C, temperature corrected to 25 °C was 1.29 × 10−5 cm2 s−1. DGT flow rates were between −14.7 and 6.50% of the flow independently monitored flow rate (weir). In comparison, grab sample flow rates diverged by 5.52 to 58.9% from the weir flow rate.

Radiation synthesis of porous calcium silicate aerogel derived from polyacrylamide hydrogel as thermal insulator

In this article, the first aerogels synthesis through cross-linked polyacrylamide (PAAm) hydrogel was reported through the use of gamma irradiation technique. Hydrogel obtained from gamma irradiation of acrylamide monomer dissolved in a solution of sodium silicate as a silicon precursor. Various irradiation doses (10 up to 60 kGy) and various acrylamide (AAm) contents (6.25, 9.37, 12.5, and 30%) were utilized in the polymerization process. The polyacrylamide (PAAm) hydrogel loaded with sodium silicate inside is soaked in a solution of CaCl2 and then heated at a temperature of 250 °C for 2 h to provide Ca-silicate aerogels with density around 0.16–0.095 gm/cm3 and porosity of 84–94.8%. Almost all samples of the obtained (Ca-Si) aerogels have porosity >80% and low thermal conductivity (thermal conductivity value around 0.114 and 0.096 W/m.K) at ambient condition. This work discusses the effects of preparation conditions like the gamma-irradiation doses and the total solids content (wt%) of PAAm on the formation of Ca-silicate aerogels. It was found that PAAm plays a crucial role in the thermal conductivity and porosity (%) of the obtained Ca-Si aerogel samples. The increasing of PAAm content (wt%) from 6.25 to 30% increased the pores (v%) from 84 to 90.5% and reduced the thermal conductivity from 0.114 to 0.096 W/(m.K). This is because the presence of PAAm at higher concentrations increases the free volume and reduces interfacial interactions to give a high-porous structure of the Ca-Si aerogel.

An environment-stable hydrogel with skin-matchable performance for human-machine interface

Ionic hydrogel-based sensors have shined a spotlight on wearable electronics. However, the sensitivity and reliability of hydrogel devices are significantly hampered by the weak adhesion of skin-sensor interface as well as inferior temperature tolerance. Here, inspired by the structure and composition of dermis, a novel skin-attachable and environment-stable hydrogel was designed by integrating collagen into the LiCl-containing chemically cross-linked polyacrylamide hydrogel. The hydrogel exhibited skin-like mechanical properties of low modulus, superior stretchability as well as excellent elasticity. Furthermore, the introduction of collagen endowed the hydrogel with robust and seamless interfaces with diverse materials, including the curved skin. As a result, the hydrogel is capable of serving as a human-machine interface for collecting reliable electrocardiography (ECG) signals and discerning various human motions, with high sensitivity (gauge factor = 10.7), fast response, negligible hysteresis as well as extensive monitoring range. Notably, the hydrogel that can mimick the temperature-tolerant mechanism of most organisms possesses persistent stabilization of adhesive, conductive, sensory and mechanical performances at subzero or ambient conditions. The skin-inspired strategy paves an effective way for the design of multifunctional materials with potential applications in next-generation electronics.

Photodegradable Polyacrylamide Gels for Dynamic Control of Cell Functions.

Cross-linked polyacrylamide hydrogels are commonly used in biotechnology and cell culture applications due to advantageous properties, such as the precise control of material stiffness and the attachment of cell adhesive ligands. However, the chemical and physical properties of polyacrylamide gels cannot be altered once fabricated. Here, we develop a photodegradable polyacrylamide gel system that allows for a dynamic control of polyacrylamide gel stiffness with exposure to light. Photodegradable polyacrylamide hydrogel networks are produced by copolymerizing acrylamide and a photocleavable ortho-nitrobenzyl (o-NB) bis-acrylate cross-linker. When the hydrogels are exposed to light, the o-NB cross-links cleave and the stiffness of the photodegradable polyacrylamide gels decreases. Further examination of the effect of dynamic stiffness changes on cell behavior reveals that in situ softening of the culture substrate leads to changes in cell behavior that are not observed when cells are cultured on presoftened gels, indicating that both dynamic and static mechanical environments influence cell fate. Notably, we observe significant changes in nuclear localization of YAP and cytoskeletal organization after in situ softening; these changes further depend on the type and concentration of cell adhesive proteins attached to the gel surface. By incorporating the simplicity and well-established protocols of standard polyacrylamide gel fabrication with the dynamic control of photodegradable systems, we can enhance the capability of polyacrylamide gels, thereby enabling cell biologists and engineers to study more complex cellular behaviors that were previously inaccessible using regular polyacrylamide gels.

Anisotropic Double-Network Hydrogels via Controlled Orientation of a Physical Sacrificial Network

We report a method to create anisotropic double-network (DN) hydrogels, through the controlled orientation of a physical sacrificial network. A cross-linked polyacrylamide hydrogel is synthesized from a solution containing a semirigid anionic polyelectrolyte. Subsequently, the gel is stretched to orient the semirigid polyelectrolyte, which does not relax in the stretched state because of the high contour length in comparison to the mesh size of the polyacrylamide network. The polyelectrolyte is then physically cross-linked with a multivalent cation, ZrCl2O, to fix the anisotropy. Anisotropy was visualized by observing birefringence and quantified by small-angle X-ray scattering. By comparing the scattering in the oriented direction versus perpendicular to the oriented direction, a structural anisotropy factor was calculated. Uniaxial tensile testing was performed on samples of varying prestretch, both parallel and perpendicular to the stretching direction. Young’s modulus, fracture stress, fracture strain, and work of extension were characterized, and the resulting mechanical anisotropy was compared to the structural anisotropy factor. We find that the anisotropy of Young’s modulus and fracture stress is directly controlled by the anisotropy of the sacrificial network, while fracture strain and work of extension show little influence from structural anisotropy. The results of this work demonstrate that prestretching of a physical sacrificial network is a controllable and simple method to create anisotropic DN hydrogels.

Terpyridine-functionalized chemically cross-linked polyacrylamide hydrogel for white emission and multistimuli-responsive behaviour

A highly efficient and multifunctional white-emitting hydrogel was fabricated using a facile copolymerization process by introducing a hydrophilic terpyridine-based chromophore into a polyacrylamide network.

Selective adsorption of tannins over small polyphenols on cross-linked polyacrylamide hydrogel beads and their regeneration with hot water

The uptake of a low dose of tannins shows health benefits. However, a high dose of tannins exhibits toxic effects. Herein cross-linked polyacrylamide hydrogel beads were prepared and used to remove or partially remove tannic acid, a model of tannins, from aqueous solutions (mimicking beverages) or alcohol-aqueous solutions (mimicking alcoholic beverages) while remaining most of the low molecular weight polyphenols such as epigallocatechin gallate (EGCG) and catechin, which are beneficial for health. The beads showed 4.1- and 77-fold higher adsorption capacities for tannic acid than for EGCG and catechin, respectively. The adsorption capacities and removal percentages were positively correlated with molecular weights of the polyphenols and hydrogen bonding alone was supposed to drive the adsorption. The adsorbed polyphenols were completely desorbed with hot water from the adsorbent, which can be attributed to the fact that elevated temperatures weakened or broken the hydrogen bonds.

The inhomogeneous diffusion of chemically crosslinked Polyacrylamide hydrogel based on poroviscosity theory

The diffusion of hydrogels is a phenomenon not only profound in novel applications of mechanical engineering but also very common in nature. Comprehensive studies of the swelling properties under stable states have been carried out in the past several years; however, ambiguities in the understanding of the kinetic behaviour of the diffusion phenomenon of hydrogels still remain. The potential applications of hydrogels are confined due to the lack of perceptiveness of the kinetic behaviour of diffusion in hydrogels. Based on our previous work, in this study, we initiate the theoretical kinetic study of the inhomogeneous diffusion of hydrogels. With poroviscosity introduced, we develop a theory for the inhomogeneous diffusion of hydrogels. After implementing this theory into the finite element solution, we could predict the water content in the hydrogel as a function of time and location. The quantitative prediction of the inhomogeneous diffusion and the formulas are given in the numerical study. Furthermore, the corresponding experiments are carried out to substantiate this theory. It can be observed that the theoretical prediction meets fairly well with our experimental data. Finally, we carry out a systematic parameter study to discuss the effect of three important parameters on the diffusion property. The increase of the interaction parameter is seen to constrain the diffusion while increase of the chemical potential is seen to facilitate the process. The change of the diffusion coefficient D, on the other hand, does not affect the process much. By comparing the conclusions above with the experimental data, we can narrow down the range of the values of χ and D.

Use of a 2.5% Cross-Linked Polyacrylamide Hydrogel in the Management of Joint Lameness in a Population of Flat Racing Thoroughbreds: A Pilot Study

Osteoarthritis is one of the most common disease processes effecting equine athletes, causing up to 60% of all lameness. This prospective longitudinal study reports on the effect of treatment of carpal and metacarpophalangeal joint lameness with 2.5% cross-linked polyacrylamide hydrogel (PAAG). A total of 49 flat-racing Thoroughbreds at a single training facility were included in the study. The results show a significant improvement in lameness grades at weeks 1 (P < .01), 4 (P < .001), 12 (P < .001), and 24 (P < .001) when compared to baseline lameness at week 0. This pilot study suggests that 2.5% cross-linked PAAG is a safe and effective joint treatment for managing joint lameness in Thoroughbred racehorses and warrants further blinded and controlled studies to fully evaluate the efficacy of the 2.5% cross-linked PAAG and its mode of action.

Linear viscoelasticity of weakly cross-linked hydrogels

Chemically cross-linked polyacrylamide (PA) hydrogels have been studied extensively, but gels with a very low cross-linker ratio have received relatively little attention. In this paper, the rheology of bis-cross-linked PA hydrogels is examined with acrylamide concentrations ca approximately 10% w/v and cross-linker to acrylamide ratios cbis/ca in the range 0.2–0.9 mmol mol−1. Linear viscoelastic responses were measured during and following gelation. The effective cross-link formation rate increases with the cross-linker ratio, with a plateau modulus that is weakly quadratic in the cross-linker ratio. The gels exhibit distinctly different features from their counterparts in the literature with higher cross-linker ratios. Plateau regions in the dynamic moduli spectra are less pronounced, and the loss tangents are several orders of magnitude higher than for gels with a higher cross-linker ratio but a comparable plateau modulus. Time-temperature superposition of viscoelastic spectra furnishes a disentanglement activation energy that decreases with increasing temperature, from ≈25 to 6kBT. Time-concentration superposition for samples prepared above the percolation threshold furnishes a critical relaxation exponent Δ≈0.38, which is much smaller than previously reported for the universal sol-gel transition. These distinct features can be attributed to the predominance of entanglements. We show that a Wiechert model with a power-law distribution of relaxation times faithfully reproduces dynamic moduli spectra from the creep compliance. Together, the results provide a foundation with which to interpret acoustic and electroacoustic rheological responses (at MHz frequencies) and the linear viscoelasticity of DNA-cross-linked gels (to be reported elsewhere).

Highly Compressible Cross-Linked Polyacrylamide Hydrogel-Enabled Compressible Zn-MnO2 Battery and a Flexible Battery-Sensor System.

The fast advancement in flexible and wearable electronics has put up with new requirements on the energy storage device with improved tolerance to deformation apart from offering power output. Despite the tremendous progress in stretchable energy storage devices, the compressional energy storage devices have indeed received limited research attention. In this work, an intrinsically compressible rechargeable battery was proposed using the Zn-MnO2 chemistry and a cross-linked polyacrylamide hydrogel electrolyte. Interestingly, the battery exhibited not only good energy storage performances but also excellent tolerance against large compressional strain without sacrificing the energy storage capability. It was also found that the ionic conductivities of the hydrogel increased with the values of the compressional strain, leading to an enhanced electrochemical performance. More importantly, upon dynamic compression, the voltage output of the battery can be very stable and reliable. Consequently, the battery assembled using the hydrogel electrolyte can be used to power a luminescent panel even with a 3 kg load on top of it. It was also demonstrated that the flexible sensor powered by our compressible battery exhibited similar and stable sensory signals compared with the same sensor powered by two commercial alkaline batteries. Furthermore, because of the excellent mechanical property of our battery, a smart wristband fabricated by integrating two battery packs and the flexible piezoresistive sensor could be powered and used to monitor the pressure exerted, demonstrating the battery's potential as the wearable power source for the flexible and wearable devices.

Volumetric hydrogel sensor enables visual and quantitative detection of sulfion

We designed and fabricated a visual volumetric sensor platform with fluorescein cross-linked amine-functionalized polyacrylamide hydrogel. The sensor undergoes volumetric response to S2− ions, enabling its visual quantitative detection by simple reading elaborately altered pipette graduation marks with the naked-eye. The sensor showed a wide linear response range to S2-, (from 1 to 100 μM of S2−). The acceptable reproducibility is demonstrated by the relative standard deviations of less than 5% in all cases. The developed sensor is suitable for rapid and onsite detection of S2- while conveniently being low cost, simple and portable. Our work provides a new avenue for the development of novel visual volumetric hydrogel sensors that can be read with the naked- eye.

Exploring the Role of Nanoparticles in Enhancing Mechanical Properties of Hydrogel Nanocomposites.

Over the past few decades, research studies have established that the mechanical properties of hydrogels can be largely impacted by the addition of nanoparticles. However, the exact mechanisms behind such enhancements are not yet fully understood. To further explore the role of nanoparticles on the enhanced mechanical properties of hydrogel nanocomposites, we used chemically crosslinked polyacrylamide hydrogels incorporating silica nanoparticles as the model system. Rheological measurements indicate that nanoparticle-mediated increases in hydrogel elastic modulus can exceed the maximum modulus that can be obtained through purely chemical crosslinking. Moreover, the data reveal that nanoparticle, monomer, and chemical crosslinker concentrations can all play an important role on the nanoparticle mediated-enhancements in mechanical properties. These results also demonstrate a strong role for pseudo crosslinking facilitated by polymer–particle interactions on the observed enhancements in elastic moduli. Taken together, our work delves into the role of nanoparticles on enhancing hydrogel properties, which is vital to the development of hydrogel nanocomposites with a wide range of specific mechanical properties.