Polycationic Hydrogel Research Articles

Ionic Potential Relaxation Effect in a Hydrogel Enabling Synapse-Like Information Processing.

The next-generation brain-like intelligence based on neuromorphic architectures emphasizes learning the ionic language of the brain, aiming for efficient brain-like computation and seamless human-computer interaction. Ionic neuromorphic devices, with ions serving as information carriers, provide possibilities to achieve this goal. Soft and biocompatible ionic conductive hydrogels are an ideal substrate for constructing ionic neuromorphic devices, but it remains a challenge to modulate the ion transport behavior in hydrogels to mimic neuroelectric signals. Here, we describe an ionic potential relaxation effect in a hydrogel device prepared by sandwiching a layer of polycationic hydrogel (CH) between two layers of neutral hydrogel (NH), allowing this device to simulate various electrical signal patterns observed in biological synapses, including short- and long-term plasticity patterns. Theoretical and experimental results show that the selective permeation and hysteretic diffusion of ions caused by the anion selectivity of the CH layer are responsible for potential relaxation. Such an effect allows us with hydrogels to enable synapse-like information processing functions, including tactile perception, learning, memory, and neuromorphic computing. Additionally, the hydrogel device can operate stably even under 180° bending and 50% tensile strain, expanding the pathway for implementing advanced brain-like intelligent systems.

Tracing Immunological Interaction in Trimethylamine N-Oxide Hydrogel-Derived Zwitterionic Microenvironment During Promoted Diabetic Wound Regeneration.

The diabetic wound healing is challenging due to the sabotaged delicate balance of immune regulation via an undetermined pathophysiological mechanism, so it is crucial to decipher multicellular signatures underlying diabetic wound healing and seek therapeutic strategies. Here, this work develops a strategy using novel trimethylamine N-oxide (TMAO)-derived zwitterionic hydrogel to promote diabetic wound healing, and explore the multi-cellular ecosystem around zwitterionic hydrogel, mapping out an overview of different cells in the zwitterionic microenvironment by single-cell RNA sequencing. The diverse cellular heterogeneity is revealed, highlighting the critical role of macrophage and neutrophils in managing diabetic wound healing. It is found that polyzwitterionic hydrogel can upregulate Ccl3+ macrophages and downregulate S100a9+ neutrophils and facilitate their interactions compared with polyanionic and polycationic hydrogels, validating the underlying effect of zwitterionic microenvironment on the activation of adaptive immune system. Moreover, zwitterionic hydrogel inhibits the formation of neutrophil extracellular traps (NETs) and promotes angiogenesis, thus improving diabetic wound healing. These findings expand the horizons of the sophisticated orchestration of immune systems in zwitterion-directed diabetic wound repair and uncover new strategies of novel immunoregulatory biomaterials.

Hetero-Polyionic Hydrogels Enable Dendrites-Free Aqueous Zn-I2 Batteries with Fast Kinetics.

Rechargeable aqueous Zn-I2 battery (ZIB) has been regarded as a promising energy storage candidate. However, the soluble polyiodides shuttling and rampant Zn dendrites growth hamper its commercial implementation. Herein, a hetero-polyionic hydrogel is designed as the electrolyte for ZIBs. On the cathode side, iodophilic polycationic hydrogel (PCH) effectively alleviates the shuttle effect and facilitates the redox kinetics of iodine species. Meanwhile, polyanionic hydrogel (PAH) towards Zn metal anode uniformizes Zn2+ flux and prevents surface corrosion by electrostatic repulsion of polyiodides. Consequently, the Zn symmetric cells with PAH electrolyte demonstrate remarkable cycling stability over 3000h at 1mA cm-2 (1 mAh cm-2 ) and 800h at 10mA cm-2 (5 mAh cm-2 ). Moreover, the Zn-I2 full cells with PAH-PCH hetero-polyionic hydrogel electrolyte deliver a low-capacity decay of 0.008 ‰ per cycle during 18000 cycles at 8 C. This work sheds light on hydrogel electrolytes design for long-life conversion-type aqueous batteries. This article is protected by copyright. All rights reserved.

Multiple bonds crosslinked antibacterial, conductive and antioxidant hydrogel adhesives with high stretchability and rapid self-healing for MRSA infected motion skin wound healing

Drug-resistant bacterial infection and low healing efficiency in motion skin wounds impose significant new requirements on design of wound dressings in terms of flexibility, self-healing, antibacterial activity, and multiple biological activities, and dressings mismatching the mechanical and biochemical properties of the wound will severely limit wound recovery. Herein, we developed a multiple bonds crosslinked antibacterial, conductive and antioxidant hydrogel adhesive with high stretchability and rapid self-healing for infected motion wound healing. The hydrogel is fabricated by one-pot photo-crosslinking the mixture of poly(glycerol sebacate)-co-poly(ethylene glycol)-g-catechol (PEGSD)/Zn2+/(3-acrylamidophenyl) boronic acid and 2-hydroxyethyl acrylate/ionic liquids (PEGSD-Zn2+/PHA-I) via multiple bonds crosslinking including coordination, hydrogen bond, phenylborate ester bond and permanent chemical bond. The in vitro antibacterial tests prove that Zn2+ incorporated polycationic hydrogel possesses excellent antibacterial property for MRSA and E. coli. Besides, the hydrogel has good cytocompatibility and antioxidation. The healing effect of hydrogel is demonstrated on the MRSA-infected mouse neck skin wound model, showing improved wound closing rate, collagen deposits and thickness of granulation tissue, due to the reduced inflammation and enhanced angiogenesis. In conclusion, the PEGSD-Zn2+/PHA-I hydrogel effectively promotes MRSA-infected motion wound healing and presents a new motion wound dressing design strategy of combining multiple biological activities and multiple bonds crosslinked network.

Extracellular-matrix-mimicked 3D nanofiber and hydrogel interpenetrated wound dressing with a dynamic autoimmune-derived healing regulation ability based on wound exudate

Dynamic regulation of wound physiological signals is the basis of wound healing. Conventional biomaterials delivering growth factors to drive wound healing leads to the passive repair of soft tissues because of the mismatch of wound healing stages. Meanwhile, the bioactivity of wound exudate is often restricted by oxidation and bacterial contamination. Herein, an extracellular matrix mimicked nanofiber/hydrogel interpenetrated network (NFHIN) was constructed with a 3D nanofibrous framework for cell immigration, and interfiled aerogel containing cross-linked hyaluronic acid and hyperbranched polyamidoamine to balance the wound microenvironment. The aerogel can collect wound exudate and transform into a polycationic hydrogel with contact-killing effects even against intracellular pathogens (bactericidal rate > 99.9% in 30 min) and real-time scavenging property of reactive oxygen species. After co-culturing with the NFHIN, the bioactivity of fibroblast in the ex vivo blister fluid was improved by 389.69%. The NFHIN showed sustainable exudate management with moisture–vapor transferring rate (6000 g m−2 ×24 h), equilibrium liquid content (75.3%), Young’s modulus (115.1 ± 7 kPa), and anti-tearing behavior similar to human skin. The NFHIN can collect and activate wound exudate, turning it from a clinical problem to an autoimmune-derived wound regulation system, showing potential for wound care in critical skin diseases.

Interaction of Short-Chain PFAS with Polycationic Gels: How Much Fluorination is Necessary for Efficient Adsorption?

The short-chain per- and polyfluorinated alkyl substances (PFAS), introduced to replace the legacy PFAS compounds, turned out to be as toxic and harmful as their longer-chain predecessors and even harder to sequester from contaminated water sources. In this work, molecular dynamics (MD) simulations are employed to investigate the adsorption mechanism of GenX, a representative compound for short-chain PFAS, on a polycationic hydrogel with various extents of fluorination in its backbone and cross-linkers. Simulations indicate that the presence of fluorinated segments next to cationic groups in the polymer gel structure provides the most efficient environment for GenX adsorption. The combination of electrostatic and hydrophobic interactions offered by the cationic-fluorophilic segments amplifies the binding of GenX molecules compared to polymer segments with nonfluorinated cationic or noncationic fluorinated segments. Moreover, such a gel demonstrates high selectivity toward GenX against its hydrogenated analogue.

Smart Polycationic Hydrogel Dressing for Dynamic Wound Healing.

It is challenging for traditional wound dressings to adapt to the complex and changeable environment, due to the lack of stable, efficient, and continuous bactericidal activity. They also cannot be satisfied in a multifunctional sensing platform to reconstruct skin sensory functions for human health monitoring. A multifunctional hydrogel dressing is developed here for the treatment of infected wounds and human health monitoring, which is based on alginate and polycation. The in situ polymerization and solvent displacement method are used to functionalize the hydrogel for the improvement of antifreezing, water retention, and environmental adaptability, as well as the adhesion and photothermal property. As a wound dressing, the as-prepared hydrogel exhibits an excellent antibacterial property against both Escherichia coli and Staphylococcus aureus. In a rat model of full-thickness wound infection, it significantly accelerates the healing of infected wounds with a high healing rate of 96.49%. In the further multifunctional sensory tests, the hydrogel shows multiple response modes of strain, pressure and temperature, and sensing stability. An idea is provided here to develop a smart hydrogel dressing that can accelerate wound healing and achieve human health monitoring.

Bio-inspired visual multi-sensing interactive ionic skin with asymmetrical adhesive, antibacterial and self-powered functions

Despite the rapid development of flexible wearable devices, the current ionic skins still remain a challenge to simultaneously realize visual dynamic display, multi-signal sensing, together with asymmetrical adhesive, antibacterial and self-powered functions for motion monitoring, thus severely limiting their practical applications in artificial intelligence and human–machine interaction. Herein, a multifunctional interactive ionic skin (MIIS) with these attractive functions is first presented by an asymmetrical double-layer structural color hydrogel (ADSCH) for visual and digital detecting human motions in real-time. The ADSCH is constructed by combining a highly stretchable, inverse opal structural polycationic hydrogel as the upper layer with a soft, adhesive polyanionic hydrogel as the lower layer using the sacrificial template and layer-by-layer polymerization methods respectively. The resultant ADSCH not only possesses electrical signal monitoring through the change of resistance, but also shows intuitive optical sensing by regulating the lattice spacing of photonic crystal under external strain and pressure stimuli at wide ranges (0–500%; 0–40 kPa). More importantly, the ADSCH is concurrently integrated with outstanding asymmetrical adhesion (adhesion strength: ∼30 kPa), antibacterial (log reduction: >4.44) and self-powered functions. Therefore, this study provides novel insights into for the design and fabrication of multifunctional interactive wearable devices.

Rational Design of Polycationic Hydrogel with Excellent Combination Functions for Flexible Wearable Electronic Devices

AbstractWith the popularization of intelligent terminals and the improvement of medical level, the development of flexible wearable electronic devices (FWEDs) with high sensitivity and excellent mechanical properties plays a vital role in human motion and health monitoring. But most of FWEDs still stuck in a difficult choice of mechanical, functional, and sensory properties. In this work, it is found a strategy for extricating such plight. Using zwitterionic and quaternary ammonium salt, a novel polycationic hydrogel [P(ImSL‐AmC)] with excellent performance is synthesized by copolymerization under photoinitiation. After optimizing conditions of synthesis, its structure and properties are characterized. It is found that the electrostatic interaction enhances the mechanical applicability of P(ImSL‐AmC), which combines high stretchability (≈500% strain) with perfect strength (≈900 kPa) successfully. It is exciting that P(ImSL‐AmC) not only exhibits excellent antibacterial activities against both E. coli and S. aureus, but also maintains transparency and flexibility at −10 °C. This polycationic hydrogel also has superior conductivity as a stretchable pressure‐strain sensor, which can accurately monitor human motion. In summary, the obtained polycationic hydrogel possesses excellent combination functions, including intelligent conductivity, mechanical adaptability, antibacterial, frost resistance, and transparency. Furthermore, the practical strategy can be applied in preparation of intelligent wearable devices and human–computer interaction.

Exchange Counterion in Polycationic Hydrogels: Tunability of Hydrophobicity, Water State, and Floating Capability for a Floating pH Device.

Smart gel materials are capable of controlling and switching swelling, water state, and wettability properties triggered by external stimuli. In this study, we fabricated a series of polyelectrolyte hydrogels bearing a 3-trimethylammoniumpropyl pendant to a methacrylamide-based backbone and examined the switchability with hydrophobic-like counteranions. The exchange between the initial chloride and camphor sulfate (CaS), dodecyl sulfate (DS), and perfluorooctanoate (PFO) counterions was investigated. The kinetics of the exchange showed that the fast exchange (within 4 h) of PFO allowed for a favorable coordination for ion pairing, resulting in a decrease in hydration. The reversibility of the exchange to the Cl− ion was only enabled for the CaS ion due to its bulkiness, while the PFO and DS hydrogels were unable to exchange, even by using tetrabutylammonium chloride, which is a structurally similar reagent, due to aggregation or the coagulates in the collapsed state of the linear tails of the counterions. The hydrogels exhibited a modulable water state and water swelling. Moreover, the hydrogels containing DS and PFO, as counterions, showed surface hydrophobic (contact angle 90°) and high hydrophobic (110°) behavior, respectively. The Raman spectrometry fluorescence with a pyrene probe indicated an increase in strong hydrogen-bonded water molecules, water confinement, and hydrophobic domains in the PFO hydrogel. Moreover, the PFO-modified hydrogel demonstrated a free-floating ability on the water surface, with a strong water repellency, showing that it has the potential to be applied in a floating pH detection device to distinguish between volatile and nonvolatile bases in a controlled manner.

Hydrogels Based on Imino-Chitosan Amphiphiles as a Matrix for Drug Delivery Systems.

This paper reports new formulations based on chitosan, citral, and diclofenac sodium salt (DCF). The central idea was to encapsulate an anionic drug into a polycationic hydrogel matrix in order to increase the intermolecular forces between them and thus to ensure slower drug release, while citral was used as a penetration enhancer to assure efficient delivery of the drug. Hydrogels without drug were also synthesized and used as a reference. The structure, morphology, and supramolecular architecture of the drug delivery systems were evaluated by FTIR spectroscopy, scanning electron microscopy, polarized optical microscopy, and wide-angle X-ray diffraction. The drug release kinetics was monitored in vitro by UV-VIS spectroscopy, in physiological conditions, while the enzymatic and hydrolytic degradability of the hydrogels were evaluated in the presence of lysozyme and phosphate buffer saline (PBS), at 37 °C. All of the data revealed that the anionic DCF was strongly anchored into the polycationic matrix and the drug was slowly released over 7 days. Moreover, the release rate can be controlled by simple variation of the molar ratio between the polycationic chitosan and lipophilic citral.

Effect of mold assemblies-induced interfaces in the mechanical actuation of electro-responsive ionic liquid-based polycationic hydrogels

This work aims the development of electro-active polycationic soft-actuators based on copolymers of 2-hydroxyethyl methacrylate (HEMA) and 1-butyl-3-vinylimidazolium chloride (BVImCl), cross-linked with N,N’-methylene bis(acrylamide), and reinforced with mesoporous silica nanoparticles. Polycationic hydrogels were obtained by free radical polymerization in aqueous solution and using mold assemblies presenting different surface properties (e.g. Teflon® and glass). Obtained results demonstrated that a mold assembly-induced effect, at the mold/polymerization solution interface, originates “surface-to-bulk” heterogeneous copolymer concentration gradients when using Teflon®-Teflon® and Teflon®-glass mold assemblies, while homogeneous hydrogel networks were obtained when using only glass mold assemblies. Results were compared with those obtained from cross-linked poly(2-hydroxyethyl methacrylate) hydrogels to prove that the observed surface-induced polymerization effect occurs only in the presence of the ionic liquid co-monomer. Hydrogels synthesized in Teflon®-Teflon® molds presented the highest mechanical response under external electric stimulus and in different aqueous media of different pH and ionic strength. On the contrary, hydrogels synthesized in glass-glass mold assemblies presented limited mechanical actuation and only when immersed in saline aqueous media. The mechanical actuation of hydrogels synthesized in Teflon®-glass molds was shown to depend on the orientation of the applied electric current. The electro-actuation response of the synthesized electro-active polycationic hydrogels was discussed based on the ion enrichment/depletion mechanism. All prepared cationic hydrogels were also able to generate small electrical currents. Overall, these results show that mold assemblies presenting different surface properties can be employed to tune the electro-actuation responsiveness of ionic liquid-based soft actuators and lead to the development of engineering devices with a broad range of applications, including artificial muscles and tissue engineering scaffolds.

A multifunctional upconverting nanoparticle incorporated polycationic hydrogel for near-infrared triggered and synergistic treatment of drug-resistant bacteria

Recently, antibiotic drug-resistant therapies have become very important due to the emergence of antibiotic-resistant bacterial strains. The development of novel antibacterial materials has received significant attention. Here, quaternized chitosan hydrogels incorporated with NaYF4:Er/Yb/Mn@photosensitizer-doped silica (UCNPs/MB) were synthesized for effective killing of both gram-positive oxacillin-resistant S. aureus (DR-S. aureus) and gram-negative kanamyclin-resistant E. coli (DR-E. coli) bacteria upon near-infrared (NIR) laser irradiation. In this system, the cationic macroporous nature of the hydrogel acts as a molecular ‘anion sponge’, which sucks the outer part of the anionic microbe membrane into the gel interior voids and causes microbe membrane disruption. By incorporating UCNPs/MB-doped silica into the hydrogel, we have combined photodynamic therapy (PDT) with quaternized chitosan to obtain a high therapeutic index via a synergistic effect. In vitro experiments have demonstrated that our system had excellent antibacterial efficiency to both DR-S. aureus and DR-E. coli bacteria. More importantly, our new synergistic treatment modality provided an excellent therapy platform for drug-resistant bacteria, which could improve antimicrobial efficiency.

Supramolecular polycationic hydrogels with high swelling capacity prepared by partial methacrylation of polyethyleneimine

Partial methacrylation of polyethyleneimine leads to novel highly hydrophilic supramolecular hydrogels that absorb and retain up to 95% of water.

Control superstructure of rigid polyelectrolytes in oppositely charged hydrogels via programmed internal stress.

Biomacromolecules usually form complex superstructures in natural biotissues, such as different alignments of collagen fibres in articular cartilages, for multifunctionalities. Inspired by nature, there are efforts towards developing multiscale ordered structures in hydrogels (recognized as one of the best candidates of soft biotissues). However, creating complex superstructures in gels are hardly realized because of the absence of effective approaches to control the localized molecular orientation. Here we introduce a method to create various superstructures of rigid polyanions in polycationic hydrogels. The control of localized orientation of rigid molecules, which are sensitive to the internal stress field of the gel, is achieved by tuning the swelling mismatch between masked and unmasked regions of the photolithographic patterned gel. Furthermore, we develop a double network structure to toughen the hydrogels with programmed superstructures, which deform reversibly under large strain. This work presents a promising pathway to develop superstructures in hydrogels and should shed light on designing biomimetic materials with intricate molecular alignments.

Binding Affinity of Thermoresponsive Polyelectrolyte Hydrogels for Charged Amphiphilic Ligands. A DSC Approach

Controlled drug binding and release stand among top requirements postulated for targeted drug delivery systems of the new generations. "Smart" polymers and gels are highly suitable for the controlled delivery due to their structural sensitivity to minor environmental variations. The aim of this work was to study thermoresponsive polyanionic and polycationic hydrogels of N-isopropylacrylamide copolymers with acrylic acid and N-aminopropylmethacrylamide in terms of their interaction with two widely used drugs, propranolol and ibuprofen. Binding energetics of these drugs by the gels in swollen and collapsed state was estimated by means of high-sensitivity differential scanning calorimetry. Thermodynamic parameters of the gel collapse (transition temperature, enthalpy, heat capacity increment, and width) were determined as a dependence of the drug concentrations. From these data the excess free energy of collapse was calculated as a function of drug concentration. Deconvolution of this function resulted in the evaluation of binding parameters and contributions from interactions of various types to the free energy of binding. The binding mechanism of both drugs to the swollen and collapsed gels was elucidated. Its main features are the cooperative character of the drug binding by the collapsed gel and the predominant role of the hydrophobicity of drugs in their affinity for the swollen gel.

Hydrogels with a macroscopic-scale liquid crystal structure by self-assembly of a semi-rigid polyion complex

Designing hydrogels with self-assembled or self-organized structures has become an attractive field of research because these hydrogels usually have robust functions and promising applications, such as in artificial tissues and optical sensors. However, the self-organized structures developed in synthetic hydrogels via molecular self-assembly are generally limited to the sub-micrometer or micrometer level, which is far from the related scale achieved in biological tissues. Therefore, it is desirable to create macroscopically ordered structures in hydrogels; these structures should greatly improve the material’s functionalities, such as their optical properties. In this review, we generally introduce our recent studies on the synthesis of hydrogels with macroscopic-scale liquid crystal structures based on the self-assembly of a semi-rigid polyanion, poly(2,2′-disulfonyl-4,4′-benzidine terephthalamide) (PBDT). Upon electrostatic interaction with multivalent cations or polycations, PBDT molecules form semi-rigid complexes or mesoscopic bundles that further self-assemble into macroscopic organized structures and are frozen by the subsequent gelation process. We have developed physical hydrogels with centimeter-scale anisotropic structures, polycationic hydrogels with millimeter-scale cylindrically symmetric structures and plate gels with cubic-packed concentric domains. This work should contribute to the development of macroscopic self-organized structures in hydrogel materials with specific functions.

A polycationic antimicrobial and biocompatible hydrogel with microbe membrane suctioning ability

Despite advanced sterilization and aseptic techniques, infections associated with medical implants have not been eradicated. Most present coatings cannot simultaneously fulfil the requirements of antibacterial and antifungal activity as well as biocompatibility and reusability. Here, we report an antimicrobial hydrogel based on dimethyldecylammonium chitosan (with high quaternization)-graft-poly(ethylene glycol) methacrylate (DMDC-Q-g-EM) and poly(ethylene glycol) diacrylate, which has excellent antimicrobial efficacy against Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus and Fusarium solani. The proposed mechanism of the antimicrobial activity of the polycationic hydrogel is by attraction of sections of anionic microbial membrane into the internal nanopores of the hydrogel, like an 'anion sponge', leading to microbial membrane disruption and then microbe death. We have also demonstrated a thin uniform adherent coating of the hydrogel by simple ultraviolet immobilization. An animal study shows that DMDC-Q-g-EM hydrogel coating is biocompatible with rabbit conjunctiva and has no toxicity to the epithelial cells or the underlying stroma.

Mesoscopic Network Structure of a Semi‐Rigid Polyion Complex Nested in a Polycationic Hydrogel

Mesoscopic Network Structure of a Semi‐Rigid Polyion Complex Nested in a Polycationic Hydrogel

Cationic poly(VCL–AETA) hydrogels and ovalbumin (OVA) release in vitro

The objective of this research is to explore the synthesis of a new family of water soluble polycationic copolymeric precursors that could be photo-crosslinked into hydrogels. The in vitro control release of ovalbumin protein (OVA) from this family of hydrogels was also studied to assess the biomedical potential of this new family polycationic hydrogels. A series of novel poly(VCL-AETA) copolymer hydrogels was fabricated in an aqueous medium via photo-induced polymerization and crosslinking of hydrophobic N-vinylcaprolactam (VCL) and hydrophilic [2-(acryloxy)ethyl]trimethylammonium chloride (AETA) monomers over a wide range of VCL to AETA feed molar ratios of 2:1, 1:1, 1:2, 1:5. N,N'-methylene bisacrylamide (MBA) was used as a crosslinker. Ovalbumin (OVA), a model antigen, was preloaded into poly(VCL-AETA) hydrogel precursors and its release profiles in pH 7.4 PBS at 37 degrees C were investigated as a function of VCL to AETA monomer feed ratios over a period of 4 weeks. The in vitro results showed that OVA initial burst and subsequent sustained releases could be controlled by 3 material parameters: the hydrophobic VCL to hydrophilic AETA monomer feed ratios, crosslinking density and hydrogel degradation rate. Thus, the hydrophobic-hydrophilic VCL-AETA hydrogel network for controlled OVA release could offer advantages over organic solvent-based single component polymer system. However, these in vitro OVA release profiles may change in an in vivo environment.