Smart Hydrogels Research Articles

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.

Hierarchically Structured Hydrogel Actuator for Microplastic Pollutant Detection and Removal

The aquatic microplastic pollution has aroused worldwide concerns due to its potential risk to biological and ecological health, especially the microplastic compound pollutants (MCPs) with amplified biotoxicity. Self-powered soft robots integrating with simultaneous MCP detection and removal capacities represent an intelligent way to clear the contaminants from water, but it is still challenging to implement these properties in one single actuating material. Here, we propose a smart light-driven hydrogel actuator with hierarchical interpenetrating networks consisting of covalently bonded polyethyleneimine and polydopamine copolymers, graphene oxide nanosheets, and poly(N-isopropylacrylamide) hydrogels, which function as adsorbents for MCPs, photothermal converters, and actuating matrix, respectively. Thanks to the integrative hierarchical structure design, the resulted actuator can behave like a soft swimming robot to simultaneously identify and adsorb MCPs, which successfully incorporates multiple functionalities without compromising the responsiveness. The hydrogel actuator features an ultralow detection limit (0.98 μM for the ferric ion), excellent adsorbing selectivity (97.09% for ferric ion-adsorbed MCPs), high adsorption (94.63%) and desorption efficiency (99.12%), and multiple and untethered photothermal actuation performances. We believe this work will shed light on a promising construction strategy of intelligent soft robots for environmental remediation applications.

Recent Advances of Stimuli-Responsive Polysaccharide Hydrogels in Delivery Systems: A Review.

Hydrogels obtained from natural polymers have received widespread attention for their excellent biocompatible property, nontoxicity, easy gelation, and functionalization. Polysaccharides can regulate the gut microbiota and improve the intestinal microenvironment, thus exerting the healthy effect of intestinal immunity. In an active substance delivery system, the extent and speed of the substance reaching its target are highly dependent on the carrier. Thus, the smart active substance delivery systems are gradually increasing. The smart polysaccharide-hydrogels possess the ability in response to external stimuli through changing their volume phase and structure, which are applied in various fields. Natural polysaccharide-based hydrogels possess excellent characteristics of environmental friendliness, good biocompatibility, and abundant sources. According to the response type, natural polysaccharide-based hydrogels are usually divided into stimulus-responsive hydrogels, including internal response (pH, temperature, enzyme, redox) and external response (light, electricity, magnetism) hydrogels. The delivery system based on polysaccharides can exert their effects in the gastrointestinal tract. At the same time, polysaccharides may also take part in regulating the brain signals through the microbiota-gut-brain axis. Therefore, natural polysaccharide-hydrogels are considered as promising biomaterials, which can be designed as delivery systems for regulating the gut-brain axis. This article reviews the research advance of stimulus-responsive hydrogels, which focus on the types, response characteristics, and applications for polysaccharide-based smart hydrogels as delivery systems.

Conductive and transparent poly (N-isopropylacrylamide) hydrogels with tunable LCST copolymerized by the green acrylamide-based deep eutectic solvent

Smart hydrogels have been widely applied in the bionic intelligent devices for the virtues of biocompatibility, well processibility, environmental sensitivity, and so on. Traditional poly(N-isopropylacrylamide) (PNIPAM) hydrogel has the native response to the temperature change, but the weak strength and narrow phase transition point have limited its applications. Moreover, the poor conductivity of PNIPAM has shields the response signals to the outside. In this work, we have put forward a facile strategy by introducing the ionic conductive deep eutectic solvent (DES) composed of acetylcholine chloride (ACh) and acrylamide (AAm). Followed by one-step copolymerization of AAm and NIPAM, the PAAm-DES/PNIPAM hydrogel formed with the tunable lowest critical solution temperature (LCST), high strength, fine transparence, and good conductivity. As a result, the hydrogel showed the high-sensitive, wide-range and stable response on the outer strain and thermal change, which can play as a sensing element in the intelligent devices. This cost-effective method will be a potential way for fabricating the environmental and multifunctional materials.

Application and Prospects of Hydrogel Additive Manufacturing.

Hydrogel has become a commonly used material for 3D and 4D printing due to its favorable biocompatibility and low cost. Additive manufacturing, also known as 3D printing, was originally referred to as rapid prototyping manufacturing. Variable-feature rapid prototyping technology, also known as 4D printing, is a combination of materials, mathematics, and additives. This study constitutes a literature review to address hydrogel-based additive manufacturing technologies, introducing the characteristics of commonly used 3D printing hydrogel methods, such as direct ink writing, fused deposition modeling, and stereolithography. With this review, we also investigated the stimulus types, as well as the advantages and disadvantages of various stimulus-responsive hydrogels in smart hydrogels; non-responsive hydrogels; and various applications of additive manufacturing hydrogels, such as neural catheter preparation and drug delivery. The opportunities, challenges, and future prospects of hydrogel additive manufacturing technologies are discussed.

Hydrogels for localized chemotherapy of liver cancer: a possible strategy for improved and safe liver cancer treatment

The systemic drug has historically been preferred for the treatment of the majority of pathological conditions, particularly liver cancer. Indeed, this mode of treatment is associated with adverse reactions, toxicity, off-target accumulation, and rapid hepatic and renal clearance. Numerous efforts have been made to design systemic therapeutic carriers to improve retention while decreasing side effects and clearance. Following systemic medication, local administration of therapeutic agents allows for higher ‘effective’ doses with fewer side effects, kidney accumulation, and clearance. Hydrogels are highly biocompatible and can be used for both imaging and therapy. Hydrogel-based drug delivery approach has fewer side effects than traditional chemotherapy and can deliver drugs to tumors for a longer time. The chemical and physical flexibility of hydrogels can be used to achieve disease-induced in situ accumulation as well as subsequent drug release and hydrogel-programmed degradation. Moreover, they can act as a biocompatible depot for localized chemotherapy when stimuli-responsive carriers are administrated. Herein, we summarize the design strategies of various hydrogels used for localized chemotherapy of liver cancer and their delivery routes, as well as recent research on smart hydrogels.

Collagen and Keratin as a Components of Hydrogels

Abstract Smart hydrogels, or stimuli-responsive hydrogels, can and should play an important role as excellent drug carriers. These three-dimensional structure materials are composed of crosslinked hydrophilic polymer chains that are able to dramatically change their volume and other properties in response to environmental stimuli, such as pH, temperature and solvent changes. The main goal of individual research projects was the development of new hydrogels based on polypeptides. These hybrid materials are crosslinked hydrophilic polymers capable of absorbing large amounts of water, saline or physiological solutions. Superabsorbent hydrogels based on natural materials are non-toxic, biocompatible and biodegradable. Unfortunately, their mechanical properties in the swollen state are weak. In this article, we present a review of literature on the synthesis of smart hydrogels based on keratin or collagen with synthetic materials.

On-site and dual-mode detection of live Vibrio parahaemolyticus in waters: A universal pathogen sensing platform based on a smart hydrogel aptasensor imbedded with gold nanoclusters

Usually, a low concentration of pathogens proliferate rapidly in waters to cause serious threats to human health. It is necessary to develop on-site and speedy assays to detect them. In this work, a smart hydrogel aptasensor was assembled in Eppendorf tubes for quantifying Vibrio parahaemolyticus (V.P). It employed a dual-mode detection strategy combining visual fluorescence (FL) and microfluidic chip (MC) methods. In this aptasensor, the hydrogel contained ATP aptamer together with gold nanoclusters (AuNCs) as signal tags, and V.P aptamer was modified on tube lids. Firstly, trace V.P in waters was specifically enriched by the lid and then hydrolyzed to release ATP which was combined with ATP aptamer in hydrogel to form ATP-aptamer complex. The complex together with AuNCs was subsequently released into the supernatant for dual-mode detection. ATP-aptamer was detected by MC and AuNCs by FL. By the assay, as low as 100 CFU·mL−1 V.P was determined by FL within 45 min and 10 CFU·mL−1 by MC. The dual-mode sensing platform exhibits the following advantages: Firstly, live pathogens were quantitatively and on-site detected. Secondly, the lid’s enrichment of V.P and signal transduction from one V.P to 1014 ATP could double-amplify signals and increase the detection efficiency. Finally, the samples quickly screened by visual FL on-site, and then accurately quantified by MC in the laboratory, which greatly shortens the detection period. It has been successfully utilized for on-site detecting V.P in aquatic waters and could be extended to other bacteria measurements through changing the relative aptamer on the tube lid.

Silicene/poly(N-isopropylacrylamide) smart hydrogels as remote light-controlled switches

Smart hydrogels with good flexibility and biocompatibility have been widely used. The common near-infrared (NIR) photothermal agents are facing a trade-off between good photothermal-conversion efficiency and high biocompatibility. Therefore, developing new metal-free photothermal agents with low cost, high biocompatibility and excellent phase stability is still in urgent need. In this study, we successfully combined poly(N-isopropylacrylamide) (PNIPAM) with the two-dimensional (2D) silicene nanosheets via the in situ polymerization method. Attributed to the thermal-responsive nature of PNIPAM and the excellent photothermal properties of 2D silicene, the obtained silicene/PNIPAM composite hydrogels exhibited dual thermal and NIR responsive properties. This smart hydrogel showed rapid, reversible and repeatable NIR light-responsive behaviors. The volume of this smart hydrogels can shrink significantly under NIR irradiation and recover to its original size without the NIR irradiation. Remote near-infrared light-controlled microfluidic pipelines and electronic switches based on obtained silicene/PNIPAM composite hydrogels were also demonstrated. This work significantly broadens the application prospects of silicene-based hydrogels in remote light-controlled devices.

Enzyme-Responsive Hydrogels as Potential Drug Delivery Systems-State of Knowledge and Future Prospects.

Fast advances in polymer science have provided new hydrogels for applications in drug delivery. Among modern drug formulations, polymeric type stimuli-responsive hydrogels (SRHs), also called smart hydrogels, deserve special attention as they revealed to be a promising tool useful for a variety of pharmaceutical and biomedical applications. In fact, the basic feature of these systems is the ability to change their mechanical properties, swelling ability, hydrophilicity, or bioactive molecules permeability, which are influenced by various stimuli, particularly enzymes. Indeed, among a great number of SHRs, enzyme-responsive hydrogels (ERHs) gain much interest as they possess several potential biomedical applications (e.g., in controlled release, drug delivery, etc.). Such a new type of SHRs directly respond to many different enzymes even under mild conditions. Therefore, they show either reversible or irreversible enzyme-induced changes both in chemical and physical properties. This article reviews the state-of-the art in ERHs designed for controlled drug delivery systems (DDSs). Principal enzymes used for biomedical hydrogel preparation were presented and different ERHs were further characterized focusing mainly on glucose oxidase-, β-galactosidase- and metalloproteinases-based catalyzed reactions. Additionally, strategies employed to produce ERHs were described. The current state of knowledge and the discussion were made on successful applications and prospects for further development of effective methods used to obtain ERH as DDSs.

Smart Hydrogel Sensors with Antifreezing, Antifouling Properties for Wound Healing.

Flexible electronic devices with biological therapeutic and sensing properties are one of the current research directions. Here, a multifunctional hydrogel for stress sensing and wound healing was prepared by a simple one-pot method and a solution replacement method. Among them, zwitterionic polymers promote wound healing by promoting the polarization of M2 macrophages, collagen deposition, and blood vessel formation. Glycerin can significantly improve the resilience and frost resistance of the hydrogel, ensuring that a sensor made using the hydrogel can work normally in a cold environment. In addition, zwitterionic polymers are highly biocompatible, providing excellent antibacterial adhesion to aid the wound healing process, and good electrical conductivity enhances sensing sensitivity and stability. Based on these properties, multifunctional hydrogels could detect human vital activities while promoting wound healing, providing new ideas for the fields of diagnosis and wound dressing.

A Smart Hydrogel with Anti-Biofilm and Anti-Virulence Activities to Treat Pseudomonas aeruginosa Infections.

Biofilm is the main culprit of refractory infections and seriously threaten to the human health. Here, a smart hydrogel consisted of norspermidine, aminoglycosides, and oxidized polysaccharide is prepared via the formation of acid-labile imine linkage to treat Pseudomonas aeruginosa biofilm infections in several animal models. The increased acidity caused by bacterial infection triggers the release of norspermidine and aminoglycosides covalently bound with the polymer scaffold. The released norspermidine inhibits biofilm formation and virulence production by regulating the quorum sensing of P. aeruginosa, while the aminoglycoside antibiotics effectively kill the released bacteria. The gel thoroughly inhibits biofilm formation on various medical devices and decreases bacteria pathogenicity. It efficiently inhibits implantation-associated biofilm infections and chronic wound infections, and shows great promise to prevent and treat biofilm-induced refractory infection in clinics.

Flytrap Inspired pH‐Driven 3D Hydrogel Actuator by Femtosecond Laser Microfabrication

AbstractWith the development of bionics and nanophotonics, hydrogel microactuators capable of responding to external stimuli to produce controllable deformations have attracted a great deal of interest. These microactuators hold significant promise in areas such as bionic devices, soft robotics, and precision sensors. It is not a trivial task to make such small devices as well as to make them work in a controlled manner. Here, inspired by the intelligent response of flytrap, a smart hydrogel microactuator based on a bionic asymmetric structure is demonstrated. The designed asymmetric microstructure is fabricated by femtosecond laser direct writing with deformation time of 1.2 s and recovery time of 0.3 s. The grasping and releasing behavior of the microactuator for micro‐objects can be realized and tuned by using pH‐triggered shape changes, demonstrating its potential for applications, such as flexible robotics, smart sensors, and microscopic manipulation.

Smart hydrogels with wide visible color tunability

Pigmentary coloration can produce viewing angle-independent uniform colors via light absorption by chromophores. However, due to the limited diversity in the changes of the molecular configuration of chromophores to undergo color change, the existing materials cannot produce a wide range of visible colors with tunable color saturation and transmittance. Herein, we propose a novel strategy to create materials with a wide visible color range and highly tunable color saturation and transmittance. We fabricated a hydrogel with poly (acrylamide-co-dopamine acrylamide) networks swollen with Fe3+-containing glycerol/water in which the covalently crosslinked polyacrylamide backbone with pendant catechols can ensure that the hydrogel maintains a very stable shape. Hydrogels containing adjustable catechol-Fe3+ coordination bonds with flexible light-interacting configuration changes can display a wide range of visible colors based on the complementary color principle. The catechol-Fe3+ complexes can dynamically switch between noncoordinated and mono-, bis- and tris-coordinated states to harvest light energy from a specific wavelength across the whole visible spectrum. Therefore, these hydrogels can be yellow, green, blue, and red, covering the three primary colors. Moreover, color saturation and transmittance can be flexibly manipulated by simply adjusting the Fe3+ content in the hydrogel networks. The versatility of these smart hydrogels has been demonstrated through diverse applications, including optical filters for color regulation and colorimetric sensors for detecting UV light and chemical vapors. This proposed smart hydrogel provides a universal color-switchable platform for the development of multifunctional optical systems such as optical filters, sensors, and detectors.

A Facile Approach for Anisotropic Hydrogel with Light-Regulated Stiffness and Its Application to Achieve Mechanical Toughening.

Many load-bearing tissues in nature obtain high toughness by fabricating anisotropic structures with spatially regulated composition and modulus at the macroscale. This inspires a toughening strategy for hydrogels based on the controlling of modulus heterogeneity. Herein, a facile approach to realize light-regulated spatial modulus heterogeneity with large contrast in hydrogels is proposed. Ferric citric acid complex (Fe3+ /CA-complex) is used as a light-responsive ionic cross-linker, which can first stiffen an alginate/polyacrylamide (Alg/PAAm) hydrogel by coordinating with the Alg to form another network, then realize light-triggered softening through photoreduction of ferric ions (Fe3+ ). Based on this, a stripe-patterned hydrogel with alternating stiff and soft segments can be fabricated through photopatterning. The modulus contrast between the stiff and soft phases can be adjusted by control of several influence factors and the maximum modulus contrast can reach up to 87times. As a result, the toughness of the stripe-patterned hydrogel is enhanced by 3.5times comparing to that hydrogel without a pattern. This approach shows great potential in the synthesis of smart hydrogels with light-programmable mechanical performances, and may be widely applicable for the hydrogels with functional groups that can coordinate with metal ions.

Smart and regeneratable Xanthan gum hydrogel adsorbents for selective removal of cationic dyes

Poly-anionic Xanthan gum-based hydrogels were synthesized and used as potent adsorbents for the removal of dye pollutants from waste water effluents. The adsorbents were synthesized by esterification of Xanthan gum with maleic anhydride, followed by thiol-ene cross-linking chemistry with 2,2′-(ethylenedioxy)diethanethiol. Methylene blue was used as model cationic dye to mimic dye polluted water. The adsorption kinetics of methylene blue by the Xanthan gum-based hydrogels was modeled by pseudo-first-order, pseudo-second-order and intraparticle diffusion models. The experimental adsorption data at 25 °C was modeled by the Langmuir isotherm. The effects of adsorption operation parameters such as the initial dye concentration, pH, ionic strength, and adsorbent dose were also investigated. The pseudo-second-order and Langmuir models were found to be the most appropriate models for the description of the adsorption kinetics and isotherm data, respectively. The Xanthan gum-based hydrogel exhibited a high adsorption capacity of up to qmax=435 mg/g (1.35 mmol/g) towards methylene blue. The incorporation of carboxylic acid groups in the Xanthan gum backbone afforded appreciable charge density at pH > 5, which can effectively facilitate the binding of cationic dye molecules. Consequently, the uptake mechanism of methylene blue by the polyanionic Xanthan hydrogel is attributed mainly to the electrostatic interactions. The Xanthan gum-based hydrogel had a remarkable selectivity for the cationic dye in binary and ternary mixtures of methylene blue with methyl orange or sunset yellow FCF. Finally, the hydrogel showed a potential to be re-used for at least for twenty times after regeneration and maintaining over 95% efficiency dye removal as well as recovery.

Smart Hydrogels for Advanced Drug Delivery Systems.

Since the last few decades, the development of smart hydrogels, which can respond to stimuli and adapt their responses based on external cues from their environments, has become a thriving research frontier in the biomedical engineering field. Nowadays, drug delivery systems have received great attention and smart hydrogels can be potentially used in these systems due to their high stability, physicochemical properties, and biocompatibility. Smart hydrogels can change their hydrophilicity, swelling ability, physical properties, and molecules permeability, influenced by external stimuli such as pH, temperature, electrical and magnetic fields, light, and the biomolecules’ concentration, thus resulting in the controlled release of the loaded drugs. Herein, this review encompasses the latest investigations in the field of stimuli-responsive drug-loaded hydrogels and our contribution to this matter.

Formulation, Characterization, and In Vitro Drug Release Study of β-Cyclodextrin-Based Smart Hydrogels.

In this study, novel pH-responsive polymeric β-cyclodextrin-graft-poly(acrylic acid/itaconic acid) hydrogels were fabricated by the free radical polymerization technique. Various concentrations of β-cyclodextrin, acrylic acid, and itaconic acid were crosslinked by ethylene glycol dimethacrylate in the presence of ammonium persulfate. The crosslinked hydrogels were used for the controlled delivery of theophylline. Loading of theophylline was conducted by the absorption and diffusion method. The fabricated network of hydrogel was evaluated by Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), X-ray diffractometry (XRD), and scanning electron microscopy (SEM). The crosslinking among hydrogel contents and drug loading by the fabricated hydrogel were confirmed by FTIR analysis, while TGA indicated a high thermal stability of the prepared hydrogel as compared to pure β-cyclodextrin and itaconic acid. The high thermal stability of the developed hydrogel indicated an increase in the thermal stability of β-cyclodextrin and itaconic acid after crosslinking. Similarly, a decrease in crystallinity of β-cyclodextrin and itaconic acid was observed after crosslinking, as evaluated by XRD analysis. SEM revealed an irregular and hard surface of the prepared hydrogel, which may be correlated with strong crosslinking among hydrogel contents. Crosslinked insoluble and uncrosslinked soluble fractions of hydrogel were evaluated by sol–gel analysis. An increase in gel fraction was seen with the increase in compositions of hydrogel contents, while a decrease in sol fraction was observed. Dynamic swelling and dissolution studies were performed in three various buffer solutions of pH 1.2, 4.6, and 7.4, respectively. Maximum swelling and drug release were observed at higher pH values as compared to the lower pH value due to the deprotonation and protonation of functional groups of the hydrogel contents; thus, the pH-sensitive nature of the fabricated hydrogel was demonstrated. Likewise, water penetration capability and polymer volume were evaluated by porosity and polymer volume studies. Increased incorporation of β-cyclodextrin, acrylic acid, and itaconic acid led to an increase in swelling, drug release, drug loading, and porosity of the fabricated hydrogel, whereas a decrease was detected with the increasing concentration of ethylene glycol dimethacrylate. Conclusively, the prepared hydrogel could be employed as a suitable and promising carrier for the controlled release of theophylline.

The effect of PEO homopolymers on the behaviours and structural evolution of Pluronic F127 smart hydrogels for controlled drug delivery systems

Understanding the structure-property relationships of drug delivery system (DDS) components is critical for their development and the prediction of bodily performance. This study investigates the effects of introducing polyethylene oxide (PEO) homopolymers, over a wide range of molecular weights, into Pluronic injectable smart hydrogel formulations. These smart DDSs promise to enhance patient compliance, reduce adverse effects and dosing frequency. Pharmaceutically, Pluronic systems are attractive due to their unique sol-gel phase transition in the body, biocompatibility, safety and ease of injectability as solutions before transforming into gel matrices at body temperature. This paper presents a systematic and comprehensive evaluation of gelation and the interplay of microscopic and macroscopic properties under both equilibrium and non-equilibrium conditions in controlled environments, as measured by rheology in conjunction with time-resolved Small Angle Neutron Scattering (SANS). The non-equilibrium conditions investigated in this work offer a better understanding of the two polymeric systems’ complex interactions affecting the matrix thermo-rheological behaviour and structure and therefore the future release of an active pharmaceutical ingredient from the injectable DDS.

IMMOBILIZATION OF LEVOTHYROXINE IN QUATERNIZED N,N-DIETYL N-METHYL CHITOSAN HYDROGEL AND CHEMICAL NATURE OF THE INTERACTION

Immobilization of a thyroid hormone substitute of L-thyroxine on chitosan-based smart hydrogel structure was performed to reduce the side effects of the required daily dose. The hydrogel was obtained by the Schiff reaction of chitosan with acetaldehyde and quaternization with methyl iodide then by ion exchange with NaCl salt. Finally, a hydrogel was obtained from the treatment of chitosan-based salt at -200C. The amount of levothyroxine immobilized by physical sorption on the hydrogel was determined by molecular electron spectroscopy on basis especially absorption peak at 227 nm. Results of IR- and UV-Vis spectroscopic analyses revealed that the interaction between levothyroxine and hydrogel occurs mainly due to hydrogen bonding and orientation forces of intermolecular interaction