Polyion Complex Hydrogels Research Articles

Solvent-induced phase separation and Hofmeister effect enhanced strong, tough, and adhesive polyion complex hydrogels

Polyion complex (PIC) hydrogels possess excellent strength and toughness due to the dynamic and synergetic energy dissipation mechanism associated with the co-existence of both strong and weak bonds, ionic and hydrogen, in their networks. On the other hand, PIC hydrogels usually exhibit poor wet adhesion properties. Furthermore, the role such dynamic energy dissipation mechanism plays in determining interfacial binding is unknown. To address these challenges, here, we report the fabrication of an adhesive PIC hydrogel, poly(sodium p-styrenesulfonate) (NaSS)/poly(acryloyloxyethyltrimethyl ammonium chloride (DAC)–co-2-vinyl-4,6-diamino-1,3,5-triazine (VDT), i.e. PNaSS/P(DAC-co-VDT), by introducing a multi-hydrogen bonding capacity functional co-monomer, VDT, and solvent-induced gel phase separation into the fabrication process. The resulting hydrogel exhibited as high as 174 kPa adhesion strength, with retained high mechanical properties, typically 1.2 MPa tensile strength, 2.12 MPa Young’s modulus, and 452% strain. The mechanical properties of PNaSS/P(DAC-co-VDT) were tunable by adjusting the content of VDT and of the total monomer concentration in hydrogel precursor solutions (Cm), as well as by taking advantage of the Hofmeister effect. The dynamic modulus spectra of PNaSS/P(DAC-co-VDT) hydrogels at different Cm’s in extended frequency windows with time–temperature superposition method (TTS) were acquired and analyzed to explore the influence of polymer entanglement on the hydrogel network structure. The microscopic structure-macroscopic mechanical property relationship of PNaSS/P(DAC-co-VDT) hydrogels at different Cm’s and immersed in different salt solutions was further studied using the Mooney-Rivlin equation and by fitting the tensile data to Creton’s viscoelastic model. This study may provide new insights into designing and constructing strong and tough PIC hydrogel-based adhesives.

PH-Induced Mechanical Transition in Polyion Complex Hydrogels: Shifting from Ionic Association to Hydrophobic Association

pH-Induced Mechanical Transition in Polyion Complex Hydrogels: Shifting from Ionic Association to Hydrophobic Association

Alginate-Chitosan Hydrogels Containing shRNA Plasmid for Inhibition of CTNNB1 Expression in Breast Cancer Cells.

The hydrogels prepared with alginate and chitosan polymers were prepared to deliver the shRNA-encoding plasmid (pshRNA) to MDA-MB-231 cells for the inhibition of β-catenin (CTNNB1), which was reported to be overexpressed in breast cancer. Polyion complex hydrogels prepared using sodium alginate and chitosan were characterized by Fourier transform infrared spectrometry (FTIR) analysis, scanning electron microscope (SEM) analysis, swelling, and degradation properties. After the release properties and serum stability of pshRNA-loaded hydrogels were determined, their cytotoxicity, transfection efficacy, and effects on CTNNB1 expression were investigated in MDA-MB-231 cells. All hydrogels were shown to protect pshRNA from the enzymatic activity of serum and to deliver pshRNA to cells efficiently. As a result of transfection studies, pshRNA-loaded hydrogels reduced CTNNB1 expression by up to 30.25%. Cell viability also decreased by 38% in cells treated with 2.5% (w/v) alginate-chitosan hydrogel containing pshRNA targeting CTNNB1. Alginate-chitosan hydrogels were shown to be a suitable matrix system for local gene delivery.

PH Responsive Strong Polyion Complex Shape Memory Hydrogel with Spontaneous Shape Changing and Information Encryption.

Polyion complex (PIC) hydrogels attract lots of studies because of the relatively definite network and excellent mechanical strength. However, the stability of the PIC hydrogel is poor in salt solutions due to the counter-ion screening effect, which restricts their applications. Besides, novel functions of the PIC hydrogels also need to be explored. In this work, a multifunctional PIC hydrogel is prepared by polymerizing a hydrophobic monomer 2-(diethylamino)ethyl methacrylate in poly(styrene sulfonic acid) aqueous solution with the presence of counter-ion NaCl. Fourier transform infrared (FTIR) spectra, water content, and mechanical properties of the hydrogel are investigated. The introduction of hydrophobic weak electrolyte into the hydrogel brings stable excellent mechanical strength even in NaCl solutions with high concentration and pH modulated softening and strengthening. Surprisingly, the hydrogel swells but is strengthened in HCl, while it shrinks but is softened in NaOH. pH induced shape memory and unique spontaneous shape changing is thus presented benefiting from this synergistic effect. Moreover, information encryption is realized on the PIC hydrogel owing to the transmittance change and the different water absorption capability of the hydrogel at different states. This new kind of PIC hydrogel proposes a new smart material in continuously actuating soft machines and secretive information transformation.

Accelerating solar desalination in brine through ion activated hierarchically porous polyion complex hydrogels

A hierarchically porous hydrogel (HPH) mediated by a polyion complex enables accelerated solar desalination performance in brine than in pure water.

Self-Healing Multiblock Copolypeptide Hydrogels via Polyion Complexation.

Diblock, triblock, and pentablock copolypeptides were designed and prepared for formation of polyion complex hydrogels in aqueous media. Increasing the number of block segments was found to allow formation of hydrogels with substantially enhanced stiffness at equivalent concentrations. Use of similar length ionic segments also allowed mixing of different block architectures to fine-tune hydrogel properties. The pentablock hydrogels possess a promising combination of high stiffness, rapid self-healing properties, and cell compatible surface chemistry that makes them promising candidates for applications requiring injectable or printable hydrogel scaffolds.

One-Step Preparation of Tough and Self-Healing Polyion Complex Hydrogels with Tunable Swelling Behaviors.

Polyion complex (PIC) hydrogels formed by charge attraction of opposite charged polymers have received unique research interest. Their conventional preparation method, with a large amount of residual salt after polymerization, requires a long-term dialysis treatment to remove the salt and toughen the gel. Here, a promising strategy for the one-step preparation of tough PIC hydrogels without dialysis after polymerization is provided. Bicarbonate and proton ions are selected as the counter ions of the cationic monomer and anionic polymers, respectively. By a CO2 -generating reaction between the counter ions, the residual salt is removed before polymerization, and thus, a PIC hydrogel with tough mechanical performance can be obtained instantly without dialysis. Due to the absence of dialysis, the tough hydrogel can be formed with a wide range of ratios for the oppositely charged polymer with distinct swelling behaviors from non-swelling to super-swelling. This tunable swelling behavior shows the possibility for shape-morphing systems from this one-step method.

Preparation and Properties of 3D Printed Alginate⁻Chitosan Polyion Complex Hydrogels for Tissue Engineering.

Three-dimensional (3D) printing holds great potential for preparing sophisticated scaffolds for tissue engineering. As a result of the shear thinning properties of an alginate solution, it is often used as 3D printing ink. However, it is difficult to prepare scaffolds with complexity structure and high fidelity, because the alginate solution has a low viscosity and alginate hydrogels prepared with Ca2+ crosslinking are mechanically weak. In this work, chitosan powders were dispersed and swelled in an alginate solution, which could effectively improve the viscosity of an alginate solution by 1.5–4 times. With the increase of chitosan content, the shape fidelity of the 3D printed alginate–chitosan polyion complex (AlCh PIC) hydrogels were improved. Scanning electron microscope (SEM) photographs showed that the lateral pore structure of 3D printed hydrogels was becoming more obvious. As a result of the increased reaction ion pairs in comparison to the alginate hydrogels that were prepared with Ca2+ crosslinking, AlCh PIC hydrogels were mechanically strong, and the compression stress of hydrogels at a 90% strain could achieve 1.4 MPa without breaking. In addition, human adipose derived stem cells (hASCs) adhered to the 3D printed AlCh PIC hydrogels and proliferated with time, which indicated that the obtained hydrogels were biocompatible and could potentially be used as scaffolds for tissue engineering.

Polyion complex hydrogels from chemically modified cellulose nanofibrils: Structure-function relationship and potential for controlled and pH-responsive release of doxorubicin

Herein, we report the fabrication of a polyion complex hydrogel from two oppositely charged derivatives of cellulose nanofibrils (CNF). CNF was produced from dissolving pulp through subsequent periodate oxidation, chemical modification, and microfluidization. Three different durations for periodate oxidation (30 min, 120 min, and 180 min) resulted in three different aldehyde contents. Further, two types of chemical modifications were introduced to react with the resulting aldehydes: chlorite oxidation to yield anionic CNF with carboxylic acid groups (DCC) and imination with Girard’s reagent T to yield cationic CNF containing quaternary ammonium groups (CDAC). Functional group contents were assessed using conductometric titration and elemental analysis, while nanofibril morphologies were assessed using atomic force microscopy (AFM). Longer durations of periodate oxidation did not yield different width profile but was found to decrease fibril length. The formation of self-standing hydrogel through mixing of DCC and CDAC dispersions was investigated. Oscillatory rheology was performed to assess the relative strengths of different gels. Self-standing hydrogels were obtained from mixture of DCC180 and CDAC180 dispersions in acetate buffer at pH 4 and 5 at a low concentration of 0.5% w/w that displayed approximately 10-fold increase in storage and loss moduli compared to those of the individual dispersions. Self-standing gels containing doxorubicin (an anticancer drug) displayed pH-responsive release profiles. At physiological pH 7.4, approximately 65% of doxorubicin was retained past a burst release regime, while complete release was observed within 5 days at pH 4. Biocompatibility of DCC180, CDAC180, and their mixture were investigated through quantification of the metabolic activity of NIH3T3 cells in vitro. No significant cytotoxicity was observed at concentrations up to 900 µg/mL. In short, the nanocellulose-based polyion complex hydrogels obtained in this study are promising nature-derived materials for biomedical applications. Statement of SignificanceWe demonstrate that polyion complex can be formed between two cellulose nanofibrils containing complementary charges. To the best of our knowledge, this is the first time that polyion complex formation between complementarily-modified cellulose nanofibrils has been reported, and the results may lead to new ideas on applications of the very promising nanocellulosic materials. The polyion complex helps form a self-standing network that is demonstrated to provide controlled and pH-responsive release of doxorubicin. Particularly, the report explores the connection between the physical properties of functionalizable nanocellulosic materials and their potential biomedical applications. Thus, the study encompasses several broad fields of materials science and engineering, chemistry, and biomedical science that we believe is in line with the readers’ interests.

Conformation-Directed Formation of Self-Healing Diblock Copolypeptide Hydrogels via Polyion Complexation.

Synthetic diblock copolypeptides were designed to incorporate oppositely charged ionic segments that form β-sheet-structured hydrogel assemblies via polyion complexation when mixed in aqueous media. The observed chain conformation directed assembly was found to be required for efficient hydrogel formation and provided distinct and useful properties to these hydrogels, including self-healing after deformation, microporous architecture, and stability against dilution in aqueous media. While many promising self-assembled materials have been prepared using disordered or liquid coacervate polyion complex (PIC) assemblies, the use of ordered chain conformations in PIC assemblies to direct formation of new supramolecular morphologies is unprecedented. The promising attributes and unique features of the β-sheet-structured PIC hydrogels described here highlight the potential of harnessing conformational order derived from PIC assembly to create new supramolecular materials.

Tough polyion-complex hydrogels from soft to stiff controlled by monomer structure

Tough hydrogels with adjustable stiffness are expected for adapting application as various biomaterials. Oppositely charged polyelectrolytes form tough and self-healing physical polyion-complex (PIC) hydrogels via formation of inter-chain ionic bonds with a wide distribution in bond strength. The strong bonds serve as permanent crosslinking to impart elasticity and the weak bonds as reversible sacrificial bonds to dissipate energy and to self-heal. In this work, we fabricate four PIC hydrogels using four positively charged trimethyl-ammonium monomers with slightly different chemical moieties and a same negatively charged polymer. The obtained PIC hydrogels all show high toughness but large difference in stiffness, extensibility, and self-recovery kinetics. With slight difference in the monomer structure of the polycations, the modulus of the hydrogels varies over two orders in magnitude, from 0.36 to 56 MPa, and the difference in elongation at break is up to five times. The presence of acryloyl moiety and methyl moiety increase the stiffness of the hydrogels. In the temperature range studied, all the four PIC hydrogels exhibit the rheological simple behaviours, following the time-temperature superposition principle. The four samples show quite different dynamic relaxation spectra over wide frequency range, revealing large difference in the strength distribution of dynamic ionic bonds. SEM observation reveals quite different phase separation structure for the four samples, in which the polymer chain stiffness should play an important role. This understanding of structure-properties of the PIC hydrogels will merit the designing of various supramolecular tough hydrogels and therefore broaden the scope of hydrogels for the applications as biomaterials.

Modulation of Self-healing of Polyion Complex Hydrogel by Ion-specific Effects

We have prepared polyion complex (PIC) hydrogel consisting of poly(3-(methacryloylamino)propyl-trimethylamonium chloride) and poly(sodium p-styrenesulfonate) polyelectrolytes via a two-step polymerization procedure and have investigated specific ion effects on the self-healing of the PIC hydrogel. Our study demonstrates that the mechanical properties of the PIC hydrogel are strongly dependent on the type of the ions doped in the hydrogel. The ion-specific effects can be used to modulate the self-healing efficiency of the PIC hydrogel. As the doped anions change from kosmotrops to chaotropes, the self-healing efficiency of the PIC hydrogel increases. A more chaotropic anion has a stronger ability to break the ionic bonds formed within the hydrogel, leading to a higher efficiency during the healing.

3D Printing of Ultratough Polyion Complex Hydrogels.

Polyion complex (PIC) hydrogels have been proposed as promising engineered soft materials due to their high toughness and good processability. In this work, we reported manufacturing of complex structures with tough PIC hydrogels based on three-dimensional (3D) printing technology. The strategy relies on the distinct strength of ionic bonding in PIC hydrogels at different stages of printing. In concentrated saline solution, PIC forms viscous solution, which can be directly extruded out of a nozzle into water, where dialyzing out of salt and counterions results in sol-gel transition to form tough physical PIC gel with intricate structures. The printability of PIC solutions was systematically investigated by adjusting the PIC material formula and printing parameters in which proper viscosity and gelation rate were found to be key factors for successful 3D printing. Uniaxial tensile tests were performed to printed single fibers and multilayer grids, both exhibiting distinct yet controllable strength and toughness. More complex 3D structures with negative Poisson's ratio, gradient grid, and material anisotropy were constructed as well, demonstrating the flexible printability of PIC hydrogels. The methodology and capability here provide a versatile platform to fabricate complex structures with tough PIC hydrogels, which should broaden the use of such materials in applications such as biomedical devices and artificial tissues.

Strong and Tough Polyion-Complex Hydrogels from Oppositely Charged Polyelectrolytes: A Comparative Study with Polyampholyte Hydrogels

Oppositely charged homopolyelectrolytes were found to form strong, tough, and self-healing polyion-complex (PIC) hydrogels, similar to polyampholytes (PA) which have opposite charges randomly distributed on the same polymer chains. The excellent mechanical performances of these two novel hydrogels are the results of dynamic ionic bonds formation between entangled polymer chains. For the PIC system, only interchain bonding occurs, while for the PA system both inter- and intrachain bonding exist. In addition, the ion pairs are expected to form stronger bonding in the PIC system than those in the PA system. In this work, we performed a comparative study of PIC hydrogels with the PA hydrogels. The PIC hydrogels are synthesized by sequential homopolymerization of cationic and anionic monomers at varied formulation, and their swelling and mechanical properties are systematically studied in comparison to the PA hydrogels that were synthesized from random copolymerization of anionic monomers and cationic monomers...

Free Reprocessability of Tough and Self-Healing Hydrogels Based on Polyion Complex.

Tough hydrogels with facile processability to reform into various shapes are required in many practical applications. In this work, we reported that a novel, tough, and self-healing physical hydrogel based on polyion complex (PIC) can be dissolved in 4 M NaCl solution to form a PIC solution. The PIC solution can be easily reprocessed into various shapes, such as thin films, sheets, fibers, and capsules, by using simple methods, such as casting and injection, while maintaining excellent mechanical properties comparable to, or even better than, the original hydrogel. The reprocessability and robust mechanical properties of PIC hydrogels are promising for practical applications in soft materials, especially in 3D/4D printing technology.

Oppositely charged polyelectrolytes form tough, self-healing, and rebuildable hydrogels.

A series of tough polyion complex hydrogels is synthesized by sequential homopolymerization of cationic and anionic monomers. Owing to the reversible interpolymer ionic bonding, the materials are self-healable under ambient conditions with the aid of saline solution. Furthermore, self-glued bulk hydrogels can be built from their microgels, which is promising for 3D/4D printing and the additive manufacturing of hydrogels.

Encapsulation of rat bone marrow stromal cells using a poly-ion complex gel of chitosan and succinylated poly(Pro-Hyp-Gly).

Encapsulation of stem cells into a three-dimensional (3D) scaffold is necessary to achieve tissue regeneration. Prefabricated 3D scaffolds, such as fibres or porous sponges, have limitations regarding homogeneous cell distribution. Hydrogels that can encapsulate cells such as animal-derived collagen gels need adjustment of the pH and/or temperature upon cell mixing. In this report, we fabricated a poly-ion complex (PIC) hydrogel of chitosan and succinylated poly(Pro-Hyp-Gly) and assessed its effect on cell viability after encapsulation of rat bone marrow stromal cells. PIC hydrogels were obtained successfully with a concentration of each precursor as low as 3.0-3.8 mg/ml. The maximum gelation and swelling ratios were achieved with an equal molar ratio (1:1) of anionic and cationic groups. Using chitosan acetate as a cationic precursor produced a PIC hydrogel with both a significantly greater gelation ratio and a better swelling ratio than chitosan chloride. Ammonium succinylated poly(Pro-Hyp-Gly) as an anionic precursor gave similar gelation and swelling ratios to those of sodium succinylated poly(Pro-Hyp-Gly). Cell encapsulation was also achieved successfully by mixing rat bone marrow stromal cells with the PIC hydrogel simultaneously during its formation. The PIC hydrogel was maintained in the culture medium for 7 days at 37°C and the encapsulated cells survived and proliferated in it. Although it is necessary to improve its functionality, this PIC hydrogel has the potential to act as a 3D scaffold for cell encapsulation and tissue regeneration. Copyright © 2015 John Wiley & Sons, Ltd.

Gelatin–pectin composite films from polyion-complex hydrogels

Preparation and properties of composite films from gelatin and low-methoxyl pectin from simultaneous reversible and permanent polyion-complex hydrogels are presented. Ionic interactions between positively charged gelatin and negatively charged pectin produce reversible physical hydrogels with homogeneous molecular arrangement that improve both mechanical and water resistance but do not alter thermal stability relative to single polymer gels. Subsequent addition of 0.3 weight percent (wt.%) glutaraldehyde crosslinks gelatin heterogeneously, due to the presence of domains with non-uniform crosslinking, as revealed by the structural analysis. Resulting interspersed permanent chemical hydrogel showed a decreased swelling attitude by nearly 10 fold relative to films from gelatin alone and further improved mechanical performance (tensile strength and elongation at break). Results demonstrate that simultaneously exploiting the specific reactivity provided by the functional groups of both biopolymers can be used to create unique new structures with improved properties and offer potential for tailoring these to a wide range of targeted applications.

Tissue-compatible and adhesive polyion complex hydrogels composed of amphiphilic phospholipid polymers

To investigate the tissue adhesive function of a hydrogel composed of biocompatible amphiphilic polymers, polymers with various architectures were prepared from 2-methacryloyloxyethyl phosphorylcholine (MPC), electrolyte monomers and hydrophobic n-butyl methacrylate (BMA). A polyion complex (PIC) hydrogel was formed within a few minutes after aqueous solutions containing the cationic and anionic MPC polymers were mixed. Provided the electrical charge of the cationic and anionic MPC polymers was approximately balanced, the PIC hydrogel existed stably in a large amount of aqueous medium. The results of the fluorescence study of the MPC polymers suggested that dissociation was suppressed and that the electrostatic interaction was enhanced in the block and graft polymers compared to the random polymers. This is due to the strategically designed architectures and the hydrophobic BMA units. Based on the results of the cytotoxicity test, the cytotoxicity of the MPC polymers was lower than that of glutaraldehyde, a cross-linker contained in aldehydetype tissue adhesives. The cationic MPC polymers demonstrated higher cytotoxicity compared to the anionic ones, which demonstrated no significant cytotoxicity at examined concentrations. The tissue adhesion of the PIC hydrogels was evaluated with a dura incision model. The results indicated that the tissue adhesion strength of the PIC hydrogel was lower than that of a commercially available fibrin glue. However, the tissue adhesion strength increased with an increase in the polymer concentration and could be controlled by the water content of the hydrogel. Although further investigation of the biocompatibility of the PIC hydrogels and control of the water content is crucial, it can be concluded that the PIC hydrogels formed by the amphiphilic MPC polymers can be promising tissue adhesives which demonstrate properties according to the architectures and chemical structures.

Preparation of a hyaluronic acid hydrogel through polyion complex formation using cationic polylactide-based microspheres as a biodegradable cross-linking agent

A novel hyaluronic acid (HA)-based hydrogel was prepared through polyion complex (PIC) formation between cationic polylactide (PLA)-based microspheres (MS+) and hyaluronic acid (HA−) as an anionic polyelectrolyte. The MS+ and HA formed a biodegradable PIC hydrogel (HA−/MS+) when mixed in aqueous media. The swelling behavior and mechanical properties of the PIC hydrogel could be controlled by changing the charge ratio between HA− and MS+. In addition, the HA−/MS+ PIC hydrogel resulted in a lower inflammatory response compared with a collagen hydrogel in vivo.