Stimuli-responsive Hydrogels Research Articles

3D printed thermo-responsive electroconductive hydrogel and its application for motion sensor

Stimulus-responsive hydrogels with excellent conductivity have been widely used in electrical, electrochemical, biomedical, and other fields. It is still a challenge to prepare gels with high conductivity. In this paper, poly (N-isopropyl acrylamide) is 3D printed by changing the rheological properties of the printing solution with clay. By forming phytic acid cross-linked polyaniline conductive polymer network in situ on the poly (N-isopropyl acrylamide) matrix, 3D printing of thermally responsive conductive hybrid hydrogels was realized. The interpenetrating polymer network structure provides an electron transport path for hydrogels. The hydrogels have high porosity, strong interaction, high electrical conductivity, high thermal response sensitivity, and significant mechanical enhancement. The results show that the swelling and mechanical properties of the gel are influenced by soaking in different concentrations. The application scenario of the hydrogel was confirmed by a temperature-sensitive switch and finger motion detection.

Temperature- and pH-Responsive Super-Absorbent Hydrogel Based on Grafted Cellulose and Capable of Heavy Metal Removal from Aqueous Solutions

In this work, we prepared highly swelling, stimuli-responsive hydrogels capable of the highly efficient adsorption of inorganic pollutants. The hydrogels were based on hydroxypropyl methyl cellulose (HPMC) grafted with acrylamide (AM) and 3-sulfopropyl acrylate (SPA) and were synthesized via the growth (radical polymerization) of the grafted copolymer chains on HPMC, which was activated by radical oxidation. These grafted structures were crosslinked to an infinite network by a small amount of di-vinyl comonomer. HPMC was chosen as a cheap hydrophilic and naturally sourced polymer backbone, while AM and SPA were employed to preferentially bond coordinating and cationic inorganic pollutants, respectively. All the gels displayed a pronounced elastic character, as well as considerably high values of stress at break (several hundred %). The gel with the highest fraction of the ionic comonomer SPA (with an AM/SPA ratio = 0.5) displayed the highest equilibrium swelling ratio (12,100%), the highest volume response to temperature and pH, and the fastest swelling kinetics, but also the lowest modulus. The other gels (with AM/SPA = 1 and 2) displayed several times higher moduli but more modest pH responses and only very modest temperature sensitivity. Cr(VI) adsorption tests indicated that the prepared hydrogels removed this species from water very efficiently: between 90 and 96% in one step. The hydrogels with AM/SPA ratios of 0.5 and 1 appeared to be promising regenerable (via pH) materials for repeated Cr(VI) adsorption.

Biocompatible stimuli responsive hydrogels of okra mucilage with acrylic acid for controlled release phytochemicals of Calendula officinalis: In vitro assay

Mucilage is a natural biopolymer present in plants. These have found a variety of applications in the areas of agriculture, food, and the pharmaceutical sector as binders, disintegrators, emulsifiers, and suspending and gelling agents, to mention a few. Mucilage has traditionally been used as such because they are biodegradable, biocompatible, and non-toxic. However, simple modifications lead to the formation of hydrogels with valuable properties when compared with those of synthetic origin. Okra mucilage was extracted and characterized for the constituent phytochemicals. The extracted okra (OKR) mucilage was chemically modified with acrylic acid (AA) to improve upon the properties of mucilage. The modifications were carried out using a cross-linker (EGDMA) followed by an initiator, potassium persulfate (KPS), in varying ratios. The polymers were standardized and optimized to show maximum swelling in distilled water, glucose, and saline solutions. The swelling was also studied at different pH levels (2, 4, 7, and 8). The developed hydrogels were characterized by FTIR, SEM, and XRD studies. The biocompatibility of the polymer was studied by evaluating the protein absorption and blood compatibility. Calendula officinalis was selected for the release study as it possesses medicinal properties. The hydrogels with maximum swelling properties were encapsulated with extracts containing phytochemicals, and an in vitro release study was carried out to study the release behavior. The encapsulation efficiency of OKR-AA hydrogels was observed to be 61% after 24 h of exposure. The in vitro studies have proved that the hydrogels have good drug release capability and can thus be explored for biomedical applications.

3D printed superparamagnetic stimuli-responsive starfish-shaped hydrogels

Magnetic-stimuli responsive hydrogels are quickly becoming a promising class of materials across numerous fields, including biomedical devices, soft robotic actuators, and wearable electronics. Hydrogels are commonly fabricated by conventional methods that limit the potential for complex architectures normally required for rapidly changing custom configurations. Rapid prototyping using 3D printing provides a solution for this. Previous work has shown successful extrusion 3D printing of magnetic hydrogels; however, extrusion-based printing is limited by nozzle resolution and ink viscosity. VAT photopolymerization offers a higher control over resolution and build-architecture. Liquid photo-resins with magnetic nanocomposites normally suffer from nanoparticle agglomeration due to local magnetic fields. In this work, we develop an optimised method for homogenously infusing up to 2 wt % superparamagnetic iron oxide nanoparticles (SPIONs) with a 10 nm diameter into a photo-resin composed of water, acrylamide and PEGDA, with improved nanoparticle homogeneity and reduced agglomeration during printing. The 3D printed starfish hydrogels exhibited high mechanical stability and robust mechanical properties with a maximum Youngs modulus of 1.8 MPa and limited shape deformation of 10% when swollen. Each individual arm of the starfish could be magnetically actuated when a remote magnetic field is applied. The starfish could grab onto a magnet with all arms when a central magnetic field was applied. Ultimately, these hydrogels retained their shape post-printing and returned to their original formation once the magnetic field had been removed. These hydrogels can be used across a wide range of applications, including soft robotics and magnetically stimulated actuators.

Preparation of stimuli-responsive hydrogel vitrimers as recyclable dye adsorbent for water purification

The concept of water purification by recyclable vitrimers through topology control has been introduced new class of polymeric materials called covalent adaptable networks (CAN), with great interest of production. Meantime, for applying the feature of stimuli-responsivity and recyclability, we synthesized poly(glycidyl methacrylate-co-methacrylic acid) copolymers (P(GMA-co-MAA)) with different molar ratios of GMA to MAA. Synthesis of copolymers and their compositions were confirmed by proton nuclear magnetic resonance 1HNMR analysis. Vitrimer hydrogels were prepared by using citric acid as crosslinker through solution casting method. Successful formation of vitrimer hydrogels was confirmed by Fourier transform infrared (FT-IR) analysis. Physical and thermal characteristics of vitrimers were investigated by differential scanning calorimetry (DSC), thermal gravimetric (TGA) analysis, and field emission scanning electron microscopy (FE-SEM). The swelling ratio behaviors of hydrogels was investigated, and the results showed that V(GMA5-co-MAA95) had maximum swelling ratio. Finally, methylene blue (MB) adsorption and desorption behavior of vitrimers and their recycled samples was investigated. The results showed that samples with the highest molar ratio of MAA had the most methylene blue adsorption in all pH values (2, 4, 7.4, and 10). The as-prepared and recycled V(GMA-co-MAA) vitrimers exhibited maximum adsorption efficiency (99.9%) at pH= 10 and initial MB concentration of 5 mg/L. Also, minimum adsorption efficiency was dedicated to pH= 2 and initial MB concentration of 2 mg/L. For both conditions adsorbent dosage and aqueous solution volume was 0.7 g and 100 mL, respectively. Also, the kinetics of adsorption was investigated by pseudo-first-order, pseudo-second-order, and intraparticle diffusion models and kinetic isotherm was evaluated by Langmuir and Freundlich models. Results showed that unlike intraparticle diffusion, pseudo-second-order and Langmuir models correlated experimental data better than on other models, suggesting these two models as the depiction for our adsorption process. SynopsisPrepared dye adsorbents are based on recyclable vitrimers which can be applied in water purification without extra plastic pollution.

Recent Progress in Advanced Hydrogel-Based Embolic Agents: From Rational Design Strategies to Improved Endovascular Embolization.

Transcatheter arterial embolization, a minimally invasive treatment to deliberately occlude the blood vessels, has become a safe and effective procedure for the management of vascular diseases and benign/malignant tumors. Particularly, hydrogel-based embolic agents have garnered much attention because of their potential to address some of the limitations of clinically used embolic agents and can be rationally designed to impart more favorable characteristics or functions. In this review, the recent progress toward the development of polymer-based hydrogels for effective endovascular embolization, including the in situ gelling hydrogels mediated by physically or chemically crosslinking, imageable hydrogels for intraprocedural and postprocedural feedback, use of hydrogels as the drug depot for local delivery of therapeutic drugs, hemostatic hydrogels inducing extrinsic or intrinsic coagulation of blood, stimuli-responsive shape memory hydrogels as the smart embolization devices, and hydrogels incorporating external-stimuli functional materials for multidisciplinary therapy, is systemically summarized. Moreover, the potential considerations of hydrogel-based embolic agents confronted in therapeutic embolization are pointed out. Finally, the perspectives for the development of more effective embolic hydrogels are also highlighted.

Experimental Demonstration of Compact Polymer Mass Transfer Device Manufactured by Additive Manufacturing with Hydrogel Integration to Bio-Mimic the Liver Functions.

In this paper, we designed and demonstrated a stimuli-responsive hydrogel that mimics the mass diffusion function of the liver. We have controlled the release mechanism using temperature and pH variations. Additive manufacturing technology was used to fabricate the device with nylon (PA-12), using selective laser sintering (SLS). The device has two compartment sections: the lower section handles the thermal management, and feeds temperature-regulated water into the mass transfer section of the upper compartment. The upper chamber has a two-layered serpentine concentric tube; the inner tube carries the temperature-regulated water to the hydrogel using the given pores. Here, the hydrogel is present in order to facilitate the release of the loaded methylene blue (MB) into the fluid. By adjusting the fluid's pH, flow rate, and temperature, the deswelling properties of the hydrogel were examined. The weight of the hydrogel was maximum at 10 mL/min and decreased by 25.29% to 10.12 g for the flow rate of 50 mL/min. The cumulative MB release at 30 °C increased to 47% for the lower flow rate of 10 mL/min, and the cumulative release at 40 °C climbed to 55%, which is 44.7% more than at 30 °C. The MB release rates considerably increased when the pH dropped from 12 to 8, showing that the lower pH had a major impact on the release of MB from the hydrogel. Only 19% of the MB was released at pH 12 after 50 min, and after that, the release rate remained nearly constant. At higher fluid temperatures, the hydrogels lost approximately 80% of their water in just 20 min, compared to a loss of 50% of their water at room temperature. The outcomes of this study may contribute to further developments in artificial organ design.

The Use of Hydrogels for the Treatment of Bone Osteosarcoma via Localized Drug-Delivery and Tissue Regeneration: A Narrative Review

Osteosarcoma is a malignant tumor of bone that leads to poor mortality and morbidity. Management of this cancer through conventional methods involves invasive treatment options that place patients at an increased risk of adverse events. The use of hydrogels to target osteosarcoma has shown promising results both in vitro and in vivo to eradicate tumor cells while promoting bone regeneration. The loading of hydrogels with chemotherapeutic drugs provides a route for site-specific targeted therapy for osteosarcoma. Current studies demonstrate tumor regression in vivo and lysis of tumor cells in vitro when exposed to doped hydrogel scaffolds. Additionally, novel stimuli-responsive hydrogels are able to react with the tissue microenvironment to facilitate the controlled release of anti-tumor drugs and with biomechanical properties that can be modulated. This narrative review of the current literature discusses both in vitro and in vivo studies of different hydrogels, including stimuli-responsive, designed to treat bone osteosarcoma. Future applications to address patient treatment for this bone cancer are also discussed.

Synthesis of NVCL-NIPAM Hydrogels Using PEGDMA as a Chemical Crosslinker for Controlled Swelling Behaviours in Potential Shapeshifting Applications.

Stimuli-responsive hydrogels have recently gained interest within shapeshifting applications due to their capabilities to expand in water and their altering swelling properties when triggered by stimuli, such as pH and heat. While conventional hydrogels lose their mechanical strength during swelling, most shapeshifting applications require materials to have mechanical strength within a satisfactory range to perform specified tasks. Thus, stronger hydrogels are needed for shapeshifting applications. Poly (N-isopropylacrylamide) (PNIPAm) and poly (N-vinyl caprolactam) (PNVCL) are the most popular thermosensitive hydrogels studied. Their close-to-physiological lower critical solution temperature (LCST) makes them superior candidates in biomedicine. In this study, copolymers made of NVCL and NIPAm and chemically crosslinked using poly (ethylene glycol) dimethacrylate (PEGDMA) were fabricated. Successful polymerisation was proven via Fourier transform infrared spectroscopy (FTIR). The effects of incorporating comonomer and crosslinker on the LCST were found minimal using cloud-point measurements, ultraviolet (UV) spectroscopy, and differential scanning calorimetry (DSC). Formulations that completed three cycles of thermo-reversing pulsatile swelling are demonstrated. Lastly, rheological analysis validated the mechanical strength of PNVCL, which was improved due to the incorporation of NIPAm and PEGDMA. This study showcases potential smart thermosensitive NVCL-based copolymers that can be applied in the biomedical shapeshifting area.

Strategies for Developing Shape-Shifting Behaviours and Potential Applications of Poly (N-vinyl Caprolactam) Hydrogels.

Stimuli-responsive hydrogels are one type of smart hydrogel, which can expand/contract in water according to changes in the surrounding environment. However, it is difficult to develop flexible shapeshifting behaviours by using a single hydrogel material. This study exploited a new method to utilise single and bilayer structures to allow hydrogel-based materials to exhibit controllable shape-shifting behaviours. Although other studies have demonstrated similar transformation behaviours, this is the first report of such smart materials developed using photopolymerised N-vinyl caprolactam (NVCL)-based polymers. Our contribution provides a straightforward method in the fabrication of deformable structures. In the presence of water, the bending behaviours (vertex-to-vertex and edge-to-edge) were achieved in monolayer squares. By controlling the content and combination of the NVCL solutions with elastic resin, the bilayer strips were prepared. The expected reversible self-bending and self-helixing behaviours were achieved in specific types of samples. In addition, by limiting the expansion time of the bilayer, the layered flower samples exhibited predictable self-curving shape transformation behaviour in at least three cycles of testing. These structures displayed the capacity of self-transformation, and the value and functionality of the produced components are reflected in this paper.

Applications of Stimuli-Responsive Hydrogels in Bone and Cartilage Regeneration.

Bone and cartilage regeneration is an area of tremendous interest and need in health care. Tissue engineering is a potential strategy for repairing and regenerating bone and cartilage defects. Hydrogels are among the most attractive biomaterials in bone and cartilage tissue engineering, mainly due to their moderate biocompatibility, hydrophilicity, and 3D network structure. Stimuli-responsive hydrogels have been a hot topic in recent decades. They can respond to external or internal stimulation and are used in the controlled delivery of drugs and tissue engineering. This review summarizes current progress in the use of stimuli-responsive hydrogels in bone and cartilage regeneration. The challenges, disadvantages, and future applications of stimuli-responsive hydrogels are briefly described.

Morph-genetic bamboo-reinforced hydrogel complex for bio-mimetic actuator

Stimuli-responsive hydrogels are most promising for the fabrication of autonomous bio-mimetic soft actuators. However, their weak actuation forces and isotropic volume change hinder their practical utilization as versatile actuators, owing to their fragility. Herein, we used the morph-genetic method to fabricate anisotropic bamboo/poly(N-isopropylacrylamide) hydrogel (ABH) complex for use as soft actuator. First of all, the bamboo fiber structure provides an anisotropic framework for the ABH actuator to achieve precise deformational programmability. Secondly, benefiting from the ultra-high directional strength (110 MPa) of bamboo, ABH actuator exhibits sufficiently robust mechanical property, which generates a powerful actuating force. Lastly, owing to the regulation of bamboo sheet and PNIPAM hydrogel, the ABH actuator not only achieves ultra-fast response speed (825°/s of the bending speed), but also has excellent synergetic performance. We demonstrate several bio-mimetic actuating devices based on ABH actuator, inspired by the intricate motions of natural organisms, to highlight how the specific materials properties and their synergy can be systematically exploited for the rational design of soft actuators. Henceforth, it is anticipated that the development of hydrogel actuators could continue to benefit from the use of various naturally-anisotropic materials, such as shape-memory polymers or liquid crystals, for the preparation of further advanced hydrogel actuators by the morph-genetic method.

PH- and Temperature-responsive Hydrogels Based on Tertiary Amine-modified Polypeptides for Stimuli-responsive Drug Delivery.

pH- and temperature-responsive hydrogels have attracted considerable attention due to their responsiveness to dual physiologically-relevant stimuli. In this study, we developed stimuli-responsive hydrogels based on monomethoxy poly(ethylene glycol) (mPEG)-polypeptide block copolymers containing various tertiary amine pendants (EEP-TAs). The EEP-TAs were synthesized via ring-opening copolymerization of α-amino acid N-carboxyanhydrides, and further modified post-polymerization with click chemistry. The EEP-TAs exhibited an α-helix-to-β-sheet transition when the pH was increased from 4.0 to 7.4. At elevated polymer concentrations, aqueous solutions of the EEP-TAs underwent thermo-induced sol-gel phase transitions, which were dependent on the pH. The hydrogels almost fully degraded within 3 weeks in the subcutaneous layer of mice and exhibited good histocompatibility in vivo. Additionally, doxorubicin (DOX)-loaded hydrogels exhibited pH-responsive drug release profiles in vitro, which were composed of rapid release at acidic pH and more sustained release at neutral pH. Thus, these polypeptide hydrogels hold potential as depots for environment-responsive delivery of therapeutic agents.

Simultaneous Sustained Drug Delivery, Tracking, and On-Demand Photoactivation of DNA-Hydrogel Formulated from a Biomass-Derived DNA Nanoparticle.

Conversion of biomass into nanoparticles for meaningful biomedical applications is a formidable proposition with excellent prospects but fewer patrons. A lack of general methodology for upscaled production and limited versatility of those nanoparticles are the main drawbacks. Herein, we report the creation of a DNA nanoparticle (DNA Dots) from onion genomic DNA (gDNA), a plant biomass source, through controlled hydrothermal pyrolysis in water without any chemicals. The DNA Dots are further formulated into a stimuli-responsive hydrogel through hybridization-mediated self-assembly with untransformed precursor gDNA. The versatility of the DNA Dots is recognized through its crosslinking ability with gDNA through its dangling DNA strands on the surface resulting from incomplete carbonization during annealing without the need for any external organic, inorganic, or polymeric crosslinkers. The gDNA-DNA Dots hybrid hydrogel is shown to be an excellent drug delivery vehicle for sustained release trackable through the inherent fluorescence of the DNA Dots. Interestingly, the DNA Dots are photoexcited with normal visible light to generate on-demand reactive oxygen species, making them exciting candidates for combination therapeutics. Most importantly, the ease with which the hydrogel is internalized in fibroblast cells with minimal cytotoxicity should encourage the nanotization of biomass as a tool for interesting sustainable biomedical applications.

Cu2+-Induced “Off–On–Off” Switching Luminescence of Cellulose-Based Luminescent Hydrogels

Stimuli-responsive luminescent hydrogels based on natural cellulose are emerging soft materials with potential applications because they simultaneously show unique luminescence properties, biocompatibility, biodegradability, and stimuli-responsiveness, and they particularly serve as functional biomaterials for bioimaging, biosensing, therapeutics, and so on. Herein, we provide a new method to prepare transparent, bulky, and multi-color luminescent hydrogels based on cellulose, ionic liquids, and lanthanide complexes (LnCs). Cellulose-based luminescent hydrogels were constructed first via dissolution–regeneration processes by dissolving cellulose in 1-allyl-3-methylimidazolium chloride (AmimCl) and then immersed in an aqueous solution of LnCs to fill the uniform porous structure of cellulose. The color-tunable emission colors ranging from red to green were emerged through regulating the molar ratio of Eu3+/Tb3+ in LnCs. Additionally, the presence of Cu2+ results in the luminescence “turn-off” process of resultant hydrogels by the naked eye through the photo-induced electron-transfer (PET) mechanism, including color and intensity, resulting in the selective recognition of Cu2+ ions. Moreover, the strong coordination between glutathione (GSH) and Cu2+ could destroy the PET process and restore the luminescence to “turn-on”. Therefore, cellulose-based hydrogels could be utilized as biocompatible and biodegradable “off–on–off” luminescence switches in aqueous medium.

Fabrication of photochromic and electrochromic (PVP-am)/WO3/MoO3 hydrogel composites and glass films with programmable shapes

Recently, the fabrication of functional and stimuli-responsive hydrogels using deep eutectic solvent derivatives is gaining tremendous scientific recognition owing to their unique self-switching properties. In this study, perfluorinated deep eutectic mixtures were prepared as the template for the synthesis of WO3/MoO3 composites. The metal oxide-based composites were further employed as a chemical crosslinking agent for the polymerization of polyvinyl pyrrolidine (PVP) and acrylamide (Am), for the construction of (PVP-Am)/WO3/MoO3 hydrogel composites. The hydrogels displayed unique morphologies and mechanical properties. The hydrophilic nature of hydrogels as well as the high concentration of dispersed WO3/MoO3 composites in the polymer network contributes to their photochromic activity and allows an immediate coloration upon exposure to light at a short time. Howbeit, the low concentration of the dispersed WO3/MoO3 composites in the dry glass membrane is responsible for the blue coloration and an extended time of photochromic response. In addition, the electrochromic behavior of the hydrogel composites displayed a strong quasi-rectangular shape potential window as well as a well-defined redox cyclic voltammetry curve when exposed to high voltage. This could be due to the photoredox property of the WO3/MoO3 composites responsible for charge transfer between the different oxidation states.

Stimulus Responsive Ocular Gentamycin-Ferrying Chitosan Nanoparticles Hydrogel: Formulation Optimization, Ocular Safety and Antibacterial Assessment [Retraction

[This retracts the article DOI: 10.2147/IJN.S254763.].

Stimulus-Responsive DNA Hydrogel Biosensors for Food Safety Detection.

Food safety has always been a major global challenge to human health and the effective detection of harmful substances in food can reduce the risk to human health. However, the food industry has been plagued by a lack of effective and sensitive safety monitoring methods due to the tension between the cost and effectiveness of monitoring. DNA-based hydrogels combine the advantages of biocompatibility, programmability, the molecular recognition of DNA molecules, and the hydrophilicity of hydrogels, making them a hotspot in the research field of new nanomaterials. The stimulus response property greatly broadens the function and application range of DNA hydrogel. In recent years, DNA hydrogels based on stimulus-responsive mechanisms have been widely applied in the field of biosensing for the detection of a variety of target substances, including various food contaminants. In this review, we describe the recent advances in the preparation of stimuli-responsive DNA hydrogels, highlighting the progress of its application in food safety detection. Finally, we also discuss the challenges and future application of stimulus-responsive DNA hydrogels.

Smart stimuli-responsive injectable gels and hydrogels for drug delivery and tissue engineering applications: A review.

Hydrogels are widely used biomaterials in the delivery of therapeutic agents, including drugs, genes, proteins, etc., as well as tissue engineering, due to obvious properties such as biocompatibility and their similarity to natural body tissues. Some of these substances have the feature of injectability, which means that the substance is injected into the desired place in the solution state and then turns into the gel, which makes it possible to administer them from a way with a minimal amount of invasion and eliminate the need for surgery to implant pre-formed materials. Gelation can be caused by a stimulus and/or spontaneously. Suppose this induces due to the effect of one or many stimuli. In that case, the material in question is called stimuli-responsive because it responds to the surrounding conditions. In this context, we introduce the different stimuli that cause gelation and investigate the different mechanisms of the transformation of the solution into the gel in them. Also, we study special structures, such as nano gels or nanocomposite gels.

Stimuli-Responsive Self-Degradable DNA Hydrogels: Design, Synthesis, and Applications.

DNA hydrogels play an increasingly important role in biomedicine and bioanalysis applications. Due to their high programmability, multifunctionality and biocompatibility, they are often used as effective carriers for packing drugs, cells, or other bioactive cargoes in vitro and in vivo. However, the stability of the DNA hydrogels prevents their in-demand rapid release of cargoes to achieve a full therapeutic effect in time. For bioanalysis, the generation of signals sometimes needs the DNA hydrogel to be rapidly degraded when sensing target molecules. To meet these requirements, stimulus-responsive DNA hydrogels are designed. By responding to different stimuli, self-degradable DNA hydrogels can switch from gel to solution for quantitative bioanalysis and precision cargo delivery. This review summarizes the recently developed innovative methods for designing stimuli-responsive self-degradable DNA hydrogels and showed their applications in the bioanalysis and biomedicines fields. Challenges, as well as prospects, are also discussed.